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1.
Proc Math Phys Eng Sci ; 478(2260): 20220073, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35510221

RESUMO

We introduce the concept of a handlebody decomposition of a three-manifold, a generalization of a Heegaard splitting, or a trisection. We show that two handlebody decompositions of a closed orientable three-manifold are stably equivalent. As an application to materials science, we consider a mathematical model of polycontinuous patterns and discuss a topological study of microphase separation of a block copolymer melt.

2.
Transplant Proc ; 50(10): 4096-4098, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30577323

RESUMO

Lipoid pneumonia is an uncommon noninfectious inflammatory lung disease characterized by lipid deposition in the alveoli, and its etiology and treatment have not been elucidated. We report the case of a 32-year-old woman who developed lipoid pneumonia 9 months after allogeneic hematopoietic stem cell transplant for chronic myelogenous leukemia in lymphoid blast crisis. She complained of progressive cough and dyspnea shortly after discontinuation of immunosuppressive therapy given for graft-vs-host disease. Computed tomography demonstrated diffuse ground-glass opacities in the lungs, and pulmonary function test revealed restrictive impairment. Bronchoalveolar lavage fluid showed milky appearance, and transbronchial lung biopsy specimen revealed foamy macrophages infiltrating the alveoli. Based on these findings, she was diagnosed as having lipoid pneumonia. Prednisolone (1 mg/kg/d) promptly improved the symptoms, pulmonary shadows, and pulmonary function. The findings and clinical course of this case suggest that lipoid pneumonia should be recognized as one of the pulmonary complications of allogeneic hematopoietic stem cell transplantation.


Assuntos
Anti-Inflamatórios/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Pneumonia Lipoide/tratamento farmacológico , Pneumonia Lipoide/etiologia , Prednisolona/uso terapêutico , Adulto , Feminino , Humanos
3.
Am J Transplant ; 17(9): 2428-2433, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28295968

RESUMO

BK polyomavirus (BKPyV) is recognized as a pathogen that causes diseases such as hemorrhagic cystitis and nephritis after allogeneic hematopoietic stem cell transplantation (HSCT) or renal transplantation. BKPyV-associated disease is thought to occur through reactivation under immunosuppression. However, the possibility of its nosocomial transmission and the clinical significance of such transmission have not been elucidated. During a 6-month period, nine adult patients (median age: 47 years) who had hematological disorders and who were treated with HSCT (n = 7) or chemotherapy (n = 2) in a single hematology department developed hemorrhagic cystitis due to BKPyV infection. The polymerase chain reaction products of BKPyV DNA obtained from each patient were sequenced. Of the nine patients, six had subtype I, 2 had subtype IV, and 1 had subtype II or III. In the alignment of sequences, four and two of the six subtype I strains were completely homologous (100%). These results strongly suggest that BKPyV has the potential to cause nosocomial infection within a medical facility, especially among recipients of HSCT. Further studies are clearly warranted to elucidate the route(s) of BKPyV transmission in order to establish optimal infection control.


Assuntos
Falência Renal Crônica/cirurgia , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Seguimentos , Taxa de Filtração Glomerular , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Imunossupressores/uso terapêutico , Testes de Função Renal , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Prognóstico , Estudos Prospectivos , Fatores de Risco
4.
Transpl Infect Dis ; 17(6): 909-14, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26426682

RESUMO

Post-transplant lymphoproliferative disorder (PTLD) is one of the life-threatening complications after hematopoietic stem cell transplantation (HSCT) and solid organ transplantation (SOT), and it is associated almost exclusively with Epstein-Barr virus (EBV). We herein report 2 cases of EBV-associated PTLD after allogeneic HSCT localized in the adrenal gland. Both patients developed adrenal tumor within 3 months after HSCT and were successfully treated with rituximab or tapering immunosuppressive agents. Both remained alive without recurrence. A literature review revealed 12 reported cases of PTLD involving the adrenal gland, but the adrenal gland was involved as one of the lesions of advanced-stage PTLD after SOT. To the best of our knowledge, this is the first report to show cases of isolated EBV-associated adrenal PTLD after HSCT. PTLD should be recognized as one of the causes of isolated adrenal tumor after HSCT.


Assuntos
Doenças das Glândulas Suprarrenais/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transtornos Linfoproliferativos/etiologia , Doenças das Glândulas Suprarrenais/tratamento farmacológico , Doenças das Glândulas Suprarrenais/patologia , Adulto , Antineoplásicos/uso terapêutico , Relação Dose-Resposta a Droga , Feminino , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Transtornos Linfoproliferativos/tratamento farmacológico , Transtornos Linfoproliferativos/patologia , Masculino , Rituximab/uso terapêutico , Adulto Jovem
5.
Genet Mol Res ; 13(2): 4159-64, 2014 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-25036160

RESUMO

Johanson-Blizzard syndrome (JBS) is a rare autosomal recessive disorder resulting from loss-of-function mutations in the UBR1 gene. JBS can be easily recognized by its unique clinical presentation (including exocrine pancreatic insufficiency, hypoplasia/aplasia of the alae nasi, congenital scalp defects, sensorineural hearing loss, growth retardation, psychomotor retardation, and anal and genitourinary anomalies). The objective of this study is to report on the first familial case of gender-discordant twins presenting JBS and a novel mutation in the UBR1 gene. We also review literature describing molecularly confirmed cases of JBS. The female twin developed refractory severe diarrhea after the second month of life and died at the age of 3 months. The male twin also developed diarrhea and failure to thrive after the 3 month of life but improved when nutrition support and pancreatic enzyme replacement was started, and he has survived into adolescence. Both patients presented typical clinical features of JBS. A homozygous nonsense mutation (c.3682C>T; p.Q1228X) in UBR1 was confirmed. Severe presentation of JBS usually involves deleterious (nonsense, frameshift, or splice-site) mutations in the UBR1 gene that are thought to completely abolish the expression of a functional protein product, as in this familial case; however, milder presentation of JBS has occasionally been observed with missense mutations in at least 1 of the 2 copies of UBR1, in which there may be residual activity of the product of this gene. Early diagnosis and adequate treatment are crucial for a favorable outcome.


Assuntos
Anus Imperfurado/genética , Anus Imperfurado/patologia , Códon sem Sentido , Displasia Ectodérmica/genética , Displasia Ectodérmica/patologia , Transtornos do Crescimento/genética , Transtornos do Crescimento/patologia , Perda Auditiva Neurossensorial/genética , Perda Auditiva Neurossensorial/patologia , Hipotireoidismo/genética , Hipotireoidismo/patologia , Deficiência Intelectual/genética , Deficiência Intelectual/patologia , Nariz/anormalidades , Pancreatopatias/genética , Pancreatopatias/patologia , Ubiquitina-Proteína Ligases/genética , Adolescente , Feminino , Humanos , Masculino , Nariz/patologia , Linhagem , Análise de Sequência de DNA
6.
Transpl Infect Dis ; 16(2): 329-32, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24494811

RESUMO

Both tacrolimus and glycopeptide antibiotics are known to be nephrotoxic, and are often concomitantly given after hematopoietic stem cell transplantation (HSCT) or solid organ transplantation. The aim of this study is to evaluate the nephrotoxicity of concomitant use of tacrolimus and glycopeptide antibiotics in HSCT recipients. We retrospectively evaluated 67 patients who received intravenous tacrolimus and teicoplanin concomitantly for >4 days after allogeneic HSCT for hematologic diseases. Therapeutic drug monitoring (TDM) was performed in all patients for both tacrolimus and teicoplanin. The median age of the patients was 48 years (range: 16-62), and the median duration of the co-administration of tacrolimus and teicoplanin was 11 days (range: 4-40). The mean serum creatinine (sCr) level tended to be elevated after the co-administration (from 0.69 ± 0.26 to 0.75 ± 0.30 mg/dL; P = 0.08); however, a 2-fold or greater increase in sCr was observed only in 2 (3.0%) patients. Increased sCr was reversible, and no patient required hemodialysis. These results suggest that the incidence of clinically significant nephrotoxicity can be minimized if the TDM of each drug is properly applied.


Assuntos
Antibacterianos/efeitos adversos , Nefropatias/induzido quimicamente , Tacrolimo/efeitos adversos , Teicoplanina/efeitos adversos , Adolescente , Adulto , Creatinina/sangue , Monitoramento de Medicamentos , Quimioterapia Combinada/efeitos adversos , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Nefropatias/sangue , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tacrolimo/administração & dosagem , Adulto Jovem
7.
Transpl Infect Dis ; 15(6): E239-42, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24134728

RESUMO

Persistent parvovirus B19 (PVB) infection has been reported sporadically in immunocompromised patients including hematopoietic stem cell and solid organ transplant recipients. However, the pathogenesis of persistent infection has yet to be fully elucidated. We report here a patient with multiple myeloma developing red cell aplasia during the hematopoietic recovery after allogeneic hematopoietic stem cell transplantation (HSCT) caused by PVB. The patient had already had PVB viremia before transplantation and remained asymptomatic. The route of PVB transmission was considered to be direct contact with the patient's family member with primary PVB infection 1 month before transplantation. Treatment with intravenous immunoglobulin resulted in prompt resolution of anemia. These findings suggest that monitoring of PVB DNA is recommended for patients undergoing HSCT and having contact with individuals with documented PVB infection, even if they are asymptomatic.


Assuntos
Eritema Infeccioso/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Parvovirus B19 Humano , Aplasia Pura de Série Vermelha/virologia , Adulto , Eritema Infeccioso/tratamento farmacológico , Eritema Infeccioso/transmissão , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Masculino , Mieloma Múltiplo/terapia
9.
Diabet Med ; 23(2): 211-5, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16433722

RESUMO

AIMS: This study aimed to investigate whether interleukin-18 (IL-18) gene polymorphisms are associated with the development of antibody against the 65-kDa isoform of recombinant human glutamic acid decarboxylase (GAD65Ab) in patients with Graves' disease. METHODS: A total of 398 unrelated Japanese patients with Graves' disease, with and without GAD65Ab, were recruited. Three single nucleotide polymorphisms in the IL-18 gene were examined and the polymorphic allele and the genotype and haplotype frequencies calculated. RESULTS: The frequency of the GG genotype at position -4675 of the IL-18 gene was significantly lower in Graves' disease patients with GAD65Ab than those without (4% vs. 24%, P = 0.0126). The -4675C allele frequency was significantly greater in patients with GAD65Ab than those without (69% vs. 53%, P = 0.0168). The homozygous -4675G/-607A/-137G haplotype was less common in Graves' disease patients with GAD65Ab than those without (4% vs. 23%, P = 0.0144). CONCLUSIONS: These findings in a Japanese population indicate that Graves' disease patients carrying the GG genotype at position -4657 of the promoter of the IL-18 gene or a gene in linkage disequilibrium with the -4675G/-607A/-137G haplotype have a low risk for the development of GAD65Ab in Graves' disease.


Assuntos
Anticorpos/imunologia , Glutamato Descarboxilase/imunologia , Doença de Graves/genética , Interleucina-18/genética , Polimorfismo de Nucleotídeo Único/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos/genética , Criança , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/imunologia , Feminino , Frequência do Gene/genética , Frequência do Gene/imunologia , Genótipo , Glutamato Descarboxilase/genética , Doença de Graves/complicações , Doença de Graves/imunologia , Humanos , Interleucina-18/imunologia , Desequilíbrio de Ligação/genética , Desequilíbrio de Ligação/imunologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/imunologia
10.
Ann Hum Genet ; 69(Pt 3): 239-52, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15845028

RESUMO

The sixth complement component (C6) has a common charge polymorphism, C6A and C6B, with similar gene frequencies in all major populations. In addition, C6B2 is also found in Japanese populations at a frequency of about 6%. Sequence analyses of the coding region of three human and ape C6 alleles indicated four nonsynonymous and three synonymous changes in C6*B2 relative to C6*A, suggesting that a recombination event occurred between C6*B2 and C6*A to give rise to C6*B. Sequence variation in a 3.86 kb region encompassing exon 3, where the causal base change of the common C6 polymorphism is found, indicated that several single nucleotide polymorphisms (SNPs) were in extensive linkage disequilibrium (LD), with little differentiation among populations. Sliding window estimates of two test statistics for neutrality revealed significant values in a subregion where the replacement coding polymorphism resides, in all three human populations. These results raise the possibility that the two common C6 alleles in human populations are maintained by balancing selection.


Assuntos
Complemento C6/genética , Polimorfismo Genético , Seleção Genética , Animais , Sequência de Bases , Genética Populacional , Humanos , Japão , Dados de Sequência Molecular , Pan troglodytes/genética , Reação em Cadeia da Polimerase , Pongo pygmaeus/genética , Recombinação Genética
11.
Ann Hum Genet ; 68(Pt 2): 110-9, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15008790

RESUMO

Polymorphisms of the promoter region (-108C/T) and the coding region (192Q/R) of the paraoxonase 1 gene (PON1) showed differences in association with cardiovascular disease risk in various populations. To characterize the genetic variation underlying these important polymorphisms, we examined DNA sequence variation both in a 1.3-kb promoter region 16.5 kb from codon 192, and in a 1.7-kb region centered on the 192Q/R polymorphic site of the coding region of PON1, in 30 Africans, 30 Europeans and 64 Japanese. We found 10 polymorphic sites and 11 haplotypes in the 1.3-kb promoter region and 10 biallelic polymorphic sites and 10 haplotypes in the 1.7-kb region. From the PON1 sequences of chimpanzees and an orangutan, the ancestral type of codon 192 was found to be R. The number of pairs of polymorphic sites between the promoter and 1.7-kb regions that were in significant linkage disequilibrium was much higher in a Japanese population than in African and European populations. In addition, the pairs of polymorphic sites in linkage disequilibrium differed among the three populations. These results suggest that some of the population differences in association with risk for coronary heart disease can be explained by population differences in haplotype frequency of PON1 haplotypes.


Assuntos
Arildialquilfosfatase/genética , Haplótipos , Desequilíbrio de Ligação , Polimorfismo Genético , Grupos Raciais/genética , Alelos , Animais , Povo Asiático/genética , Sequência de Bases , População Negra/genética , Doença das Coronárias/genética , Predisposição Genética para Doença , Variação Genética , Humanos , Pan troglodytes/genética , Polimorfismo de Nucleotídeo Único , Pongo pygmaeus/genética , Regiões Promotoras Genéticas , População Branca/genética
12.
Clin Genet ; 64(5): 439-43, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-14616769

RESUMO

We have investigated the genetic basis for the Hp0 phenotype amongst 123 randomly selected Ghanaians. A total of 17 individuals were determined to be Hp0 phenotype, based on the classical method for Hp phenotyping of Hb-supplemented plasma. Out of the 17 Hp0 individuals, nine subjects were further classified as ahaptoglobinaemic and eight as hypohaptoglobinaemic by Western blots and double immunodiffusion. We identified three previously known base substitutions (A-55G, A-61C and T-104A) and three new ones (C-101G, T-191G and C-242T) within the 5' flanking region of the Hp gene. The A-61C base substitution significantly decreased transcriptional activity and was associated strongly with Hp2 allele and ahaptoglobinaemia. The C-101G substitution was similar in transcriptional activity to the wild-type and was associated with Hp1S allele and hypohaptoglobinaemia. The Hpdel allele seen in Asian populations was absent. We conclude that the Hp0 phenotype in Ghana has a genetic basis that differs significantly from that seen in Asia.


Assuntos
Haptoglobinas/deficiência , Haptoglobinas/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Substituição de Aminoácidos , Feminino , Frequência do Gene , Gana , Haplótipos , Humanos , Masculino , Fenótipo
14.
Med Hypotheses ; 60(4): 550-1, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12615520

RESUMO

The polyol pathway consists of two enzymes aldose reductase (AR) and sorbitol dehydrogenase (SDH); the former is the first enzyme in the polyol pathway, that catalyzes the reduction of glucose to sorbitol, the latter is the second one, that converts sorbitol to fructose using by NAD(+) as a cofactor. We along with others have recently found that SDH activity, the second step in the polyol pathway, might make a greater contribution to the etiology of diabetic retinopathy than does the first step involving AR. In this paper, we propose a novel hypothesis that polymorphisms of SDH gene may be correlated with SDH gene expression levels in diabetic retinas, thus being a valuable genetic marker for diabetic retinopathy.


Assuntos
Retinopatia Diabética/genética , Predisposição Genética para Doença , L-Iditol 2-Desidrogenase/genética , Polimorfismo Genético , Aldeído Redutase/genética , Genótipo , Humanos , Regiões Promotoras Genéticas , Sorbitol/metabolismo
15.
Ann Hum Genet ; 66(Pt 2): 139-44, 2002 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12174217

RESUMO

We performed phenotyping of human phosphoglucomutase 3 (PGM(3)) and screening for mutations in the human N-acetylglucosamine-phosphate mutase gene (AGM(1)) to identify PGM(3) as AGM(1). By sequencing the coding region of AGM(1), two alleles containing a G or A base at nucleotide 1396, that can respectively encode aspartic acid or asparagine at codon 466, were identified. Cell extracts of COS7 cells after transfection with the pcDNA 3.1(+) plasmid containing an AGM(1) allele with 1396G or 1396A showed similar electrophoretic patterns to the PGM(3) 1 or PGM(3) 2 protein, respectively, with the isozyme detection method used for PGM(3) phenotyping. The genotypes determined by the two alleles of AGM(1) coincided exactly with the PGM(3) phenotypes in 20 individuals. We also investigated the allele frequency of the AGM(1) nucleotide polymorphism in a Japanese population by DNA sequencing and found that the frequencies of alleles 1396G and 1396A were similar to previously reported PGM(3) *1 and PGM(3) *2 frequencies. Overall, the facts that the AGM(1) gene product shows PGM activity, AGM(1) is polymorphic, the electrophoretic mobility is similar between AGM(1) allele-specific products and PGM(3) 1 and 2 proteins, PGM(3) phenotypes and AGM(1) genotypes completely coincide in 20 individuals, and AGM(1) allele frequencies are similar to those of PGM(3) *1 and PGM(3) *2 in Japanese populations, suggest that PGM(3) is identical to AGM(1).


Assuntos
Fosfoglucomutase/genética , Fosfotransferases (Fosfomutases)/genética , Alelos , Substituição de Aminoácidos , Animais , Células COS , Chlorocebus aethiops , Clonagem Molecular , Análise Mutacional de DNA , Eletroforese em Gel de Ágar , Frequência do Gene , Genótipo , Humanos , Isoenzimas/genética , Isoenzimas/metabolismo , Japão , Fenótipo , Fosfoglucomutase/metabolismo , Fosfotransferases (Fosfomutases)/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transfecção
17.
Int J Clin Pharmacol Res ; 22(3-4): 67-71, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12837042

RESUMO

Pigment epithelium-derived factor (PEDF) has recently been shown to be the most potent inhibitor of angiogenesis in the mammalian eye. We, along with others, have very recently found that loss of PEDF is involved in the development and progression of diabetic retinopathy. However, there are no studies on the allelic effects of PEDF gene polymorphism in diabetic retinopathy. In this study, we investigated whether a functional amino acid change, a methionine to threonine polymorphism (Met72Thr polymorphism) of the PEDF gene, is associated with microangiopathy in 143 patients with diabetes. We found that there were no significant associations between PEDF Met72Thr gene polymorphism and diabetic microangiopathy. These observations suggest that these genetic variants might not be involved in the mechanism of diabetic microangiopathy in patients with diabetes.


Assuntos
Angiopatias Diabéticas/genética , Proteínas do Olho/genética , Fatores de Crescimento Neural , Polimorfismo Genético , Proteínas/genética , Serpinas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Substituição de Aminoácidos , Feminino , Humanos , Masculino , Metionina/genética , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Treonina/genética
19.
Genetics ; 158(2): 747-56, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11404338

RESUMO

The coding sequences ( approximately 1 kb) of FUT2 [ABO-Secretor type alpha(1,2)fucosyltransferase] and of FUT6 [plasma alpha(1,3)fucosyltransferase] were analyzed for allelic polymorphism by direct sequencing in five populations. The nucleotide diversities of FUT2 estimated from pairwise sequence differences were 0.0045, 0.0042, 0.0042, 0.0009, and 0.0008 in Africans, European-Africans, Iranians, Chinese, and Japanese, respectively. The nucleotide diversities of FUT6 were 0.0024, 0.0016, 0.0015, 0.0017, and 0.0020 in Africans, European-Africans, Iranians, Chinese, and Japanese, respectively. At FUT2, excesses in pairwise sequence differences compared to the number of polymorphic sites as indicated by a significantly positive Tajima's D were observed in European-Africans and in Iranians. The data do not fit expectations of the equilibrium neutral model with an infinite number of sites. On the other hand, Tajima's D's at FUT6 in each of the five populations and at FUT2 in Africans, Chinese, and Japanese were not significantly different from zero. F(ST) between the Asians and the others measured at FUT2 was higher than at FUT6. These results suggest that natural selection was responsible for the generation of the FUT2 polymorphism in European-Africans and in Iranians.


Assuntos
Fucosiltransferases/genética , Polimorfismo Genético , Alelos , Animais , Humanos , Modelos Genéticos , Pan troglodytes , Galactosídeo 2-alfa-L-Fucosiltransferase
20.
Kidney Int ; 59(2): 471-80, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11168929

RESUMO

BACKGROUND: Caveolae are plasma membrane invaginations that have a diameter of 40 to 60 nm. Recent evidences have demonstrated that caveolae contain a variety of signal transduction molecules. Caveolin is a marker protein of caveolae and has been proposed to play a negative regulatory role in signal transduction. The aim of this study was to investigate the behavior of caveolae and caveolin in experimental glomerulonephritis, the localization of both platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta) receptors in the caveolae membrane, and the regulation of caveolin expression in cultured mesangial cells. METHODS: The expression of caveolin-1 was examined by immunoblotting and immunohistology using anti-caveolin antibody in anti-Thy-1 nephritis. The caveolae membrane fraction of mesangial cells was isolated by sucrose gradient method and expression of PDGF receptor and TGF-beta receptor were detected by immunoblotting. The effects of mitogens such as phorbol 12-myristate 13-acetate (PMA) and PDGF on the expression of caveolin-1 protein and mRNA were also examined in cultured mesangial cells. RESULTS: Caveolin-1 was mainly expressed in glomeruli and was significantly up-regulated in anti-Thy-1 nephritis rat kidney. In cultured mesangial cells, the membrane invaginations of caveolae were revealed by electron microscopy. PDGF receptors abounded in the caveolae membrane and rapidly changed their subcellular distribution after ligand stimulation. In contrast, TGF-beta receptors abounded in the non-caveolae membrane and did not change after ligand stimulation. Decreases in caveolin-1 protein, which were associated with increases in mRNA expression after the exposure of PMA or PDGF-BB, suggested an increased turnover of caveolin-1 in mesangial cells stimulated by mitogens. CONCLUSION: To our knowledge, this electron microscopical study is the first to demonstrate the presence of caveolae in cultured mesangial cells. Caveolae integrate PDGF receptors, and caveolin-1 may play a role in the pathogenesis of the mesangial proliferative glomerular diseases through PDGF signaling.


Assuntos
Cavéolas/ultraestrutura , Caveolinas/metabolismo , Mesângio Glomerular/ultraestrutura , Glomerulonefrite Membranoproliferativa/metabolismo , Glomerulonefrite Membranoproliferativa/patologia , Rim/metabolismo , Animais , Cavéolas/metabolismo , Caveolina 1 , Membrana Celular/metabolismo , Membrana Celular/ultraestrutura , Células Cultivadas , Mesângio Glomerular/efeitos dos fármacos , Mesângio Glomerular/metabolismo , Mesângio Glomerular/patologia , Membranas Intracelulares/metabolismo , Ligantes , Masculino , Fator de Crescimento Derivado de Plaquetas/farmacologia , Ratos , Ratos Wistar , Receptores do Fator de Crescimento Derivado de Plaquetas/metabolismo , Acetato de Tetradecanoilforbol/farmacologia , Distribuição Tecidual , Fator de Crescimento Transformador beta/metabolismo
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