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1.
Andrology ; 8(2): 434-441, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31479588

RESUMO

BACKGROUND: The routine genetic analysis for diagnosing male infertility has not changed over the last twenty years, and currently available tests can only determine the etiology of 4% of unselected infertile patients. Thus, to create new diagnostic assays, we must better understand the molecular and genetic mechanisms of male infertility. Although next-generation sequencing allows for simultaneous analysis of hundreds of genes and the discovery of novel candidates related to male infertility, so far only a few gene candidates have enough sound evidence to support the gene-disease relationship. OBJECTIVE: Since complementary studies are required to validate genes, we aimed to analyze the presence of potentially pathogenic rare variants in a set of candidate genes related to azoospermia in a hitherto understudied South American population. SUBJECTS AND METHODS: We performed whole exome sequencing in a group of 16 patients with non-obstructive azoospermia from Ribeirão Preto, Brazil. Based on a recent systematic review of monogenic causes of male infertility, we selected a set of 37 genes related to azoospermia, Sertoli-Cell-Only histology, and spermatogenic arrest to analyze. The identified variants were confirmed by Sanger sequencing, and their functional consequence was predicted by in silico programs. RESULTS: We identified potential pathogenic variants in seven genes in six patients. Two variants, c.671A>G (p.(Asn224Ser)) in DMRT1 and c.91C>T (p.(Arg31Cys)) in REC8, have already been described in association with azoospermia. We also found new variants in genes that already have moderate evidence of being linked to spermatogenic failure (TEX15, KLHL10), in genes with limited evidence (DNMT3B, TEX14) and in one novel promising candidate gene that has no evidence so far (SYCE1L). DISCUSSION: Although this study included a small number of patients, the process of rationally selecting genes allowed us to detect rare potentially pathogenic variants, providing supporting evidence for validating candidate genes associated with azoospermia.


Assuntos
Sequenciamento do Exoma/métodos , Infertilidade Masculina/genética , Adulto , Predisposição Genética para Doença/genética , Humanos , Masculino
2.
Braz J Med Biol Res ; 43(8): 799-805, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20725696

RESUMO

Endometriosis is a complex and multifactorial disease. Chromosomal imbalance screening in endometriotic tissue can be used to detect hot-spot regions in the search for a possible genetic marker for endometriosis. The objective of the present study was to detect chromosomal imbalances by comparative genomic hybridization (CGH) in ectopic tissue samples from ovarian endometriomas and eutopic tissue from the same patients. We evaluated 10 ovarian endometriotic tissues and 10 eutopic endometrial tissues by metaphase CGH. CGH was prepared with normal and test DNA enzymatically digested, ligated to adaptors and amplified by PCR. A second PCR was performed for DNA labeling. Equal amounts of both normal and test-labeled DNA were hybridized in human normal metaphases. The Isis FISH Imaging System V 5.0 software was used for chromosome analysis. In both eutopic and ectopic groups, 4/10 samples presented chromosomal alterations, mainly chromosomal gains. CGH identified 11q12.3-q13.1, 17p11.1-p12, 17q25.3-qter, and 19p as critical regions. Genomic imbalances in 11q, 17p, 17q, and 19p were detected in normal eutopic and/or ectopic endometrium from women with ovarian endometriosis. These regions contain genes such as POLR2G, MXRA7 and UBA52 involved in biological processes that may lead to the establishment and maintenance of endometriotic implants. This genomic imbalance may affect genes in which dysregulation impacts both eutopic and ectopic endometrium.


Assuntos
Aberrações Cromossômicas , DNA/análise , Endometriose/genética , Doenças Ovarianas/genética , Adulto , Endometriose/patologia , Feminino , Humanos , Perda de Heterozigosidade , Pessoa de Meia-Idade , Hibridização de Ácido Nucleico/genética , Doenças Ovarianas/patologia , Reação em Cadeia da Polimerase
3.
Braz. j. med. biol. res ; 43(8): 799-805, Aug. 2010. tab, ilus
Artigo em Inglês | LILACS | ID: lil-554954

RESUMO

Endometriosis is a complex and multifactorial disease. Chromosomal imbalance screening in endometriotic tissue can be used to detect hot-spot regions in the search for a possible genetic marker for endometriosis. The objective of the present study was to detect chromosomal imbalances by comparative genomic hybridization (CGH) in ectopic tissue samples from ovarian endometriomas and eutopic tissue from the same patients. We evaluated 10 ovarian endometriotic tissues and 10 eutopic endometrial tissues by metaphase CGH. CGH was prepared with normal and test DNA enzymatically digested, ligated to adaptors and amplified by PCR. A second PCR was performed for DNA labeling. Equal amounts of both normal and test-labeled DNA were hybridized in human normal metaphases. The Isis FISH Imaging System V 5.0 software was used for chromosome analysis. In both eutopic and ectopic groups, 4/10 samples presented chromosomal alterations, mainly chromosomal gains. CGH identified 11q12.3-q13.1, 17p11.1-p12, 17q25.3-qter, and 19p as critical regions. Genomic imbalances in 11q, 17p, 17q, and 19p were detected in normal eutopic and/or ectopic endometrium from women with ovarian endometriosis. These regions contain genes such as POLR2G, MXRA7 and UBA52 involved in biological processes that may lead to the establishment and maintenance of endometriotic implants. This genomic imbalance may affect genes in which dysregulation impacts both eutopic and ectopic endometrium.


Assuntos
Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Aberrações Cromossômicas , DNA , Endometriose/genética , Doenças Ovarianas/genética , Endometriose/patologia , Perda de Heterozigosidade , Hibridização de Ácido Nucleico/genética , Doenças Ovarianas/patologia , Reação em Cadeia da Polimerase
4.
Drug Discov Ther ; 3(2): 71-6, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22495480

RESUMO

Nonsteroidal anti-inflammatory drug (NSAID)-induced injury on gastrointestinal tract is well documented, and jejunal inflammation caused by indomethacin in rats is a broadly used experimental model of enteritis. We evaluated the effect of oral curcumin, a compound known to possess anti-inflammatory and anti-oxidant properties, on indomethacin-induced enteritis in the rat. Curcumin (50, 100, and 300 mg/kg) was given to rats by oral gavage 48, 24, and 1 h before enteritis was induced by intragastric administration of 20 mg/kg indomethacin. After 24 h, intestinal macroscopic lesions, myeloperoxidase activity and lipid peroxidation levels were assessed. Curcumin at the dose of 50 mg/kg was uneffective, while at the dose of 100 and 300 mg/kg significantly reduced macroscopic damage caused by indomethacin. By contrast, curcumin at all tested doses was unable to modify indomethacin-induced increases of myeloperoxidase and lipid peroxidation. Curcumin (100 and 300 mg/kg) significantly increased lipid peroxidation level in normal intestinal tissues of rats. Present data show that oral curcumin protects against macroscopic injury induced by indomethacin, leaving unaffected neutrophil infiltration and oxidative cell damage, thus suggesting that this beneficial effect is due to mechanisms not involving anti-inflammatory or antioxidant activities.

5.
Zygote ; 16(1): 29-38, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18221579

RESUMO

The objective of this article was to estimate quantitative differences for GAPDH transcripts and poly(A) mRNA: (i) between oocytes collected from cumulus-oocyte complexes (COCs) qualified morphologically as grades A and B; (ii) between grade A oocytes before and after in vitro maturation (IVM); and (iii) among in vitro-produced embryos at different developmental stages. To achieve this objective a new approach was developed to estimate differences between poly(A) mRNA when using small samples. The approach consisted of full-length cDNA amplification (acDNA) monitored by real-time PCR, in which the cDNA from half of an oocyte or embryo was used as a template. The GAPDH gene was amplified as a reverse transcription control and samples that were not positive for GAPDH transcripts were discarded. The fold differences between two samples were estimated using delta Ct and statistical analysis and were obtained using the pairwise fixed reallocation randomization test. It was found that the oocytes recovered from grade B COCs had quantitatively less poly(A) mRNA (p<0.01) transcripts compared with grade A COCs (1 arbitrary unit expression rate). In the comparison with immature oocytes (1 arbitrary unit expression rate), the quantity of poly(A) mRNA did not change during IVM, but declined following IVF and varied with embryo culture (p<0.05). Amplification of cDNA by real-time PCR was an efficient method to estimate differences in the amount of poly(A) mRNA between oocytes and embryos. The results obtained from individual oocytes suggested an association between poly(A) mRNA abundance and different morphological qualities of oocytes from COCs. In addition, a poly(A) mRNA profile was characterized from oocytes undergoing IVM, fertilization and blastocyst heating.


Assuntos
Fase de Clivagem do Zigoto , Embrião de Mamíferos/fisiologia , Perfilação da Expressão Gênica , Oócitos/fisiologia , RNA Mensageiro/genética , Animais , Blastocisto , Bovinos , Feminino , Fertilização in vitro , Masculino , RNA Mensageiro/metabolismo , Espermatozoides/citologia , Espermatozoides/metabolismo
6.
Neurogastroenterol Motil ; 19(8): 668-74, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17640182

RESUMO

A protective role of the transient potential vanilloid receptor 1 (TRPV1) in intestinal inflammation induced by dinitrobenzene sulphonic acid (DNBS) has been recently demonstrated. Curcumin, the major active component of turmeric, is also able to prevent and ameliorate the severity of the damage in DNBS-induced colitis. We evaluated the possibility that curcumin (45 mg kg(-1) day p.o. for 2 days before and 5 days after the induction of colitis) was able to reduce DNBS-induced colitis in mice, by acting as a TRPV1 agonist. Macroscopic damage score, histological damage score and colonic myeloperoxidase (MPO) activity were significantly lower (by 71%, 65% and 73%, respectively; P < 0.01), in animals treated with curcumin compared with untreated animals. Capsazepine (30 mg kg(-1), i.p.), a TRPV1 receptor antagonist, completely abolished the protective effects of curcumin. To extend these data in vitro, Xenopus oocytes expressing rat TRPV1 were examined. Capsaicin-evoked currents (3.3 micromol L(-1)) disappeared subsequent either to removal of the agonist or subsequent to the addition of capsazepine. However, curcumin (30 micromol L(-1)) was ineffective both as regard direct modification of cell membrane currents and as regard interference with capsaicin-mediated effects. As sensitization of the TRPV1 receptor by mediators of inflammation in damaged tissues has been shown previously, our results suggest that in inflamed, but not in normal tissue, curcumin can interact with the TRPV1 receptor to mediate its protective action in DNBS-induced colitis.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Colite/tratamento farmacológico , Colite/fisiopatologia , Curcumina/farmacologia , Canais de Cátion TRPV/fisiologia , Animais , Benzenossulfonatos , Capsaicina/análogos & derivados , Capsaicina/farmacologia , Membrana Celular/fisiologia , Colite/induzido quimicamente , Masculino , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Camundongos , Camundongos Endogâmicos BALB C , Oócitos/fisiologia , Peroxidase/metabolismo , Índice de Gravidade de Doença , Canais de Cátion TRPV/antagonistas & inibidores , Xenopus
7.
Clin Drug Investig ; 27(8): 573-81, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17638398

RESUMO

BACKGROUND: The renal safety of tenofovir in HIV-infected children has not been well studied. In paediatrics, prediction of glomerular filtration rate (GFR) is usually obtained by the Schwartz equation; the Cockcroft-Gault equation is considered more appropriate in children aged >12 years, but can be misleading in younger children. The aims of this study were to assess renal safety and GFR changes as estimated by the Schwartz and Cockcroft-Gault equations in HIV-infected children treated with tenofovir for 96 weeks. METHODS: Several parameters of glomerular and tubular function were prospectively assessed (at baseline and at weeks 24, 48, 72 and 96) in 27 HIV-infected children (aged 4.9-18.0 years) receiving a tenofovir-containing antiretroviral regimen. GFR was estimated using Schwartz and Cockcroft-Gault equations in children younger and older than 12 years, respectively. RESULTS: No child experienced a grade 1 (> or =44 micromol/L) or higher increase in serum creatinine or a grade 1 (< or =0.71 mmol/L) or higher hypophosphataemia. Serum bicarbonate values were in the normal range for age at baseline. Mean serum creatinine, serum phosphorus and serum bicarbonate values remained unchanged. No child showed proteinuria, microalbuminuria or glycosuria at baseline or during the study period. The mean urinary protein/creatinine, albumin/creatinine, alpha(1)-microglobulin/creatinine and maximal tubular phosphate reabsorption (TmPO(4)/GFR) ratios remained unchanged. Up to week 96, no patient experienced a significant decrease in GFR, as estimated by the more appropriate formula for age. CONCLUSION: Through 96 weeks, we found no evidence of impaired glomerular or tubular renal function in tenofovir-treated HIV-infected children.


Assuntos
Adenina/análogos & derivados , Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Nefropatias/induzido quimicamente , Organofosfonatos/efeitos adversos , Adenina/efeitos adversos , Adenina/uso terapêutico , Adolescente , Fármacos Anti-HIV/uso terapêutico , Criança , Pré-Escolar , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Infecções por HIV/virologia , Humanos , Nefropatias/fisiopatologia , Masculino , Organofosfonatos/uso terapêutico , Estudos Prospectivos , Tenofovir
8.
Braz J Med Biol Res ; 40(6): 793-7, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17581677

RESUMO

Pregnancy loss can be caused by several factors involved in human reproduction. Although up to 50% of cases remain unexplained, it has been postulated that the major cause of failed pregnancy is an error of embryo implantation. Transmembrane mucin-1 (MUC-1) is a glycoprotein expressed on the endometrial cell surface which acts as a barrier to implantation. The gene that codes for this molecule is composed of a polymorphic tandem repeat of 60 nucleotides. Our objective was to determine if MUC-1 genetic polymorphism is associated with implantation failure in patients with a history of recurrent abortion. The study was conducted on 10 women aged 25 to 35 years with no history of successful pregnancy and with a diagnosis of infertility. The control group consisted of 32 patients aged 25 to 35 years who had delivered at least two full-term live children and who had no history of abortions or fetal losses. MUC-1 amplicons were obtained by PCR and observed on agarose and polyacrylamide gel after electrophoresis. Statistical analysis showed no significant difference in the number of MUC-1 variable number of tandem repeats between these groups (P > 0.05). Our results suggest that there is no effect of the polymorphic MUC-1 sequence on the implantation failure. However, the data do not exclude MUC-1 relevance during embryo implantation. The process is related to several associated factors such as the mechanisms of gene expression in the uterus, specific MUC-1 post-translational modifications and appropriate interactions with other molecules during embryo implantation.


Assuntos
Aborto Habitual/genética , Implantação do Embrião/genética , Infertilidade Feminina/genética , Mucina-1/genética , Polimorfismo Genético , Adulto , Estudos de Casos e Controles , Eletroforese em Gel de Poliacrilamida , Feminino , Humanos , Reação em Cadeia da Polimerase , Gravidez
9.
Braz. j. med. biol. res ; 40(6): 793-797, June 2007. ilus
Artigo em Inglês | LILACS | ID: lil-452679

RESUMO

Pregnancy loss can be caused by several factors involved in human reproduction. Although up to 50 percent of cases remain unexplained, it has been postulated that the major cause of failed pregnancy is an error of embryo implantation. Transmembrane mucin-1 (MUC-1) is a glycoprotein expressed on the endometrial cell surface which acts as a barrier to implantation. The gene that codes for this molecule is composed of a polymorphic tandem repeat of 60 nucleotides. Our objective was to determine if MUC-1 genetic polymorphism is associated with implantation failure in patients with a history of recurrent abortion. The study was conducted on 10 women aged 25 to 35 years with no history of successful pregnancy and with a diagnosis of infertility. The control group consisted of 32 patients aged 25 to 35 years who had delivered at least two full-term live children and who had no history of abortions or fetal losses. MUC-1 amplicons were obtained by PCR and observed on agarose and polyacrylamide gel after electrophoresis. Statistical analysis showed no significant difference in the number of MUC-1 variable number of tandem repeats between these groups (P > 0.05). Our results suggest that there is no effect of the polymorphic MUC-1 sequence on the implantation failure. However, the data do not exclude MUC-1 relevance during embryo implantation. The process is related to several associated factors such as the mechanisms of gene expression in the uterus, specific MUC-1 post-translational modifications and appropriate interactions with other molecules during embryo implantation.


Assuntos
Adulto , Feminino , Humanos , Gravidez , Aborto Habitual/genética , /genética , Implantação do Embrião/genética , Infertilidade Feminina/genética , Polimorfismo Genético , Estudos de Casos e Controles , Eletroforese em Gel de Poliacrilamida , Reação em Cadeia da Polimerase
10.
J Anim Breed Genet ; 124(1): 42-6, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17302961

RESUMO

MUC1 is a transmembrane glycoprotein expressed on the apical surfaces of the uterine epithelial tissue with predicted functions in protection and cell-cell adhesion. These properties are closely related with the repetitive region [variable number of tandem repeats (VNTR)] of the extracellullar domain and with the O-glycosylation in their serine and threonine residues. This study describes a polymerase chain reaction (PCR) protocol to analyse MUC1 bovine genetic polymorphism and demonstrates the existence of a VNTR within the sites for O-glycosylation. Oligonucleotide primers based on the Bos taurus mucin (MUC1) gene sequence GenBank AF399757 were used to amplify five VNTR MUC1 alleles from a study group of 56 pure Nelore bovines. The number of repeats varied between 10 and 24, being more prevalent than the alleles with less number of repeats. The DNA sequence analysis revealed two repeats and one of them presented 100% homology with the bovine consensus sequence already reported. The second repeat showed codons that translate to serine and proline amino acids, which are conserved in the MUC1 of several species. This study is the first description of allelic variation and the VNTR structure in the Nelore breed MUC1 gene, and we suggest that this genetic variability can be tested for association with variation in reproductive traits in Nelore cattle.


Assuntos
Bovinos/genética , Mucina-1/genética , Polimorfismo Genético , Animais , Sequência de Bases , Primers do DNA , Frequência do Gene , Repetições Minissatélites/genética , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Homologia de Sequência
11.
Braz J Med Biol Res ; 37(11): 1683-7, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15517085

RESUMO

Neuroblastoma, the most common extracranial tumor in childhood, has a wide spectrum of clinical and biological features. The loss of heterozygosity within the 9p21 region has been reported as a prognostic factor. Two tumor suppressor genes located in this region, the CDKN2B/p15 and CDKN2A/p16 (cyclin-dependent kinase inhibitors 2B and 2A, respectively) genes, play a critical role in cell cycle progression and are considered to be targets for tumor inactivation. We analyzed CDKN2B/p15 and CDKN2A/p16 gene alterations in 11 patients, who ranged in age from 4 months to 13 years (male/female ratio was 1.2:1). The most frequent stage of the tumor was stage IV (50%), followed by stages II and III (20%) and stage I (10%). The samples were submitted to the multiplex PCR technique for homozygous deletion analysis and to single-strand conformation polymorphism and nucleotide sequencing for mutation analysis. All exons of both genes were analyzed, but no deletion was detected. One sample exhibited shift mobility specific for exon 2 in the CDKN2B/p15 gene, not confirmed by DNA sequencing. Homozygous deletions and mutations are not involved in the inactivation mechanism of the CDKN2B/p15 and CDKN2A/p16 genes in neuroblastoma; however, these two abnormalities do not exclude other inactivation pathways. Recent evidence has shown that the expression of these genes is altered in this disease. Therefore, other mechanisms of inactivation, such as methylation of promoter region and unproperly function of proteins, may be considered in order to estimate the real contribution of these genes to neuroblastoma genesis or disease progression.


Assuntos
Proteínas de Ciclo Celular/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , DNA de Neoplasias/análise , Deleção de Genes , Mutação/genética , Neuroblastoma/genética , Proteínas Supressoras de Tumor/genética , Adolescente , Criança , Pré-Escolar , Inibidor de Quinase Dependente de Ciclina p15 , Progressão da Doença , Feminino , Humanos , Lactente , Masculino , Dados de Sequência Molecular , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples
12.
Braz. j. med. biol. res ; 37(11): 1683-1687, Nov. 2004. tab
Artigo em Inglês | LILACS | ID: lil-385883

RESUMO

Neuroblastoma, the most common extracranial tumor in childhood, has a wide spectrum of clinical and biological features. The loss of heterozygosity within the 9p21 region has been reported as a prognostic factor. Two tumor suppressor genes located in this region, the CDKN2B/p15 and CDKN2A/p16 (cyclin-dependent kinase inhibitors 2B and 2A, respectively) genes, play a critical role in cell cycle progression and are considered to be targets for tumor inactivation. We analyzed CDKN2B/p15 and CDKN2A/p16 gene alterations in 11 patients, who ranged in age from 4 months to 13 years (male/female ratio was 1.2:1). The most frequent stage of the tumor was stage IV (50 percent), followed by stages II and III (20 percent) and stage I (10 percent). The samples were submitted to the multiplex PCR technique for homozygous deletion analysis and to single-strand conformation polymorphism and nucleotide sequencing for mutation analysis. All exons of both genes were analyzed, but no deletion was detected. One sample exhibited shift mobility specific for exon 2 in the CDKN2B/p15 gene, not confirmed by DNA sequencing. Homozygous deletions and mutations are not involved in the inactivation mechanism of the CDKN2B/p15 and CDKN2A/p16 genes in neuroblastoma; however, these two abnormalities do not exclude other inactivation pathways. Recent evidence has shown that the expression of these genes is altered in this disease. Therefore, other mechanisms of inactivation, such as methylation of promoter region and unproperly function of proteins, may be considered in order to estimate the real contribution of these genes to neuroblastoma genesis or disease progression.


Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Inibidor p16 de Quinase Dependente de Ciclina , Proteínas de Ciclo Celular/genética , DNA de Neoplasias/análise , Deleção de Genes , Mutação/genética , Neuroblastoma/genética , Proteínas Supressoras de Tumor/genética , Progressão da Doença , Dados de Sequência Molecular , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples
13.
Reprod Biomed Online ; 8(4): 477-82, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15149576

RESUMO

The transmembrane mucin glycoprotein (MUC1) has an anti-adhesive role, and functions to maintain a non-receptive uterine state. A polymorphic variation of the MUC1 gene has been associated with female infertility due to suspected failure of embryo implantation, based on the significant greater size of the lower allele observed in infertile women. The aim of this study was to confirm this preliminary observation using long polymerase chain reaction (PCR), which has amplified the 60-bp polymorphic variable number of tandem repeat (VNTR) associated to the binding domain of the MUC1 glycoprotein. DNA samples were obtained from 20 women, 10 fertile and 10 infertile, and the VNTR region was amplified through a long PCR procedure. The VNTR size range from 1.6 to 2.9 kb (22-44 motifs). The average size for the lower allele was 1.69 kb for both groups, and for the upper allele was 2.35 and 2.49 kb (P > 0.05) for fertile and infertile groups respectively. The VNTR polymorphism of the MUC1 gene was not associated with female infertility, although its significance cannot be discarded. It is suggested that other regulatory molecules and signals may interact with the MUC1 gene variations, favouring endometrial receptivity and embryo attachment.


Assuntos
Infertilidade Feminina/genética , Mucina-1/genética , Polimorfismo Genético , Alelos , Motivos de Aminoácidos , Sequência de Bases , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Repetições Minissatélites/genética , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Estrutura Terciária de Proteína
14.
Clin Genet ; 61(5): 380-3, 2002 May.
Artigo em Inglês | MEDLINE | ID: mdl-12081724

RESUMO

Deletions of chromosome 22q11.2 are recognized as the main cause of a number of clinical phenotypes, including velocardiofacial syndrome (VCFS) and DiGeorge syndrome (DGS). Velocardiofacial syndrome is a relatively common developmental disorder that is characterized by craniofacial anomalies and conotruncal heart defects. Most 22q11.2 deletions occur sporadically, although the deletion may be transmitted in some cases. The present performed a molecular analysis in one family including a patient with clinical diagnosis of VCFS and his sister with a suggestive phenotype. Six polymorphic 22q11.2 markers (i.e. D22S420, D22S264, D22S941, D22S306, D22S425 and D22S257) were used for genotype analysis of the DNA from the patients and unaffected relatives. The results revealed a 22q11.2 deletion in the patient and his sister from one of six markers (i.e. D22S941). Genotype analysis demonstrated that the deletion in this sib was of maternal origin. The results suggest that the mother probably has gonadal mosaicism. The other relatives present normal DNA profiles for all markers. These results have implications for genetic counseling because of a risk of transmission by germ cells carrying the deletion, even when parents present with a normal DNA profile in their blood cells.


Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 22 , Anormalidades Craniofaciais/genética , Cardiopatias Congênitas/genética , Feminino , Genótipo , Células Germinativas , Humanos , Recém-Nascido , Masculino , Mosaicismo
15.
Mutat Res ; 472(1-2): 51-8, 2000 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-11113697

RESUMO

Increasing applications of electromagnetic fields are of great concern with regard to public health. Several in vitro studies have been conducted to detect effects of microwave exposure on the genetic material leading to negative or questionable results. The micronucleus (MN) assay which is proved to be a useful tool for the detection of radiation exposure-induced cytogenetic damage was used in the present study to investigate the genotoxic effect of microwaves in human peripheral blood lymphocytes in vitro exposed in G(0) to electromagnetic fields with different frequencies (2.45 and 7.7GHz) and power density (10, 20 and 30mW/cm(2)) for three times (15, 30 and 60min). The results showed for both radiation frequencies an induction of micronuclei as compared to the control cultures at a power density of 30mW/cm(2) and after an exposure of 30 and 60min. Our study would indicate that microwaves are able to cause cytogenetic damage in human lymphocytes mainly for both high power density and long exposure time.


Assuntos
Ciclo Celular/efeitos da radiação , Linfócitos/efeitos da radiação , Testes para Micronúcleos , Micro-Ondas , Células Cultivadas , Relação Dose-Resposta à Radiação , Campos Eletromagnéticos , Humanos , Linfócitos/citologia , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Fase de Repouso do Ciclo Celular
16.
Int J Cosmet Sci ; 22(3): 201-6, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18503475

RESUMO

We tested an OTC formulation versus placebo in a double-blind trial to evaluate its ability to improve elasticity and firmness of the skin. The clinical non-invasive evaluation in 20 volunteers shows: 1. No adverse reactions such as itching or irritation 2. Efficacy and cosmetic acceptibility of the test cream 3. An increase in electrical capacitance (moisture content) even though without statistical significance. This result is not surprising because the patients had healthy skin and were relatively young (aged 20-25) 4. A very significant improvement in the biomechanical properties (extensibility and firmness) of the skin. This increase was statistically significant (P < 0.02) The main components of the cream (boswellic acids, Sylibin and Centella asiatica extracts) were formulated as complexes with lyso-phospholipids and soya bean non-saponifiable lipids.

17.
Environ Mol Mutagen ; 34(1): 64-8, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10462727

RESUMO

Cytochalasin B-blocked binucleated human lymphocytes from a healthy male donor were used to detect micronucleus induction and other aneuploidy events (chromosome loss and gain) after treatment with griseofulvin (GF), estramustine (EM), and sodium orthovanadate (Na(3)VO(4)). A two-color FISH was performed by using centromeric probes for chromosome 2 (FITC labeled) and the X chromosome (TRITC labeled) to measure chromosome loss and gain events in binucleated cells. GF induced mainly aneuploid binucleates involving the X chromosome, but this was not associated with preferential loss of one of the two chromosomes. EM preferentially induced aneuploidy of chromosome 2, and Na(3)VO(4) of the X chromosome. Our results indicate that chromosome malsegregation events (chromosome loss and/or gain) are probably not randomly induced, suggesting that different mechanisms leading to aneuploidy may be either chromosome-dependent or compound- and dose- related.


Assuntos
Aneuploidia , Estramustina/farmacologia , Griseofulvina/farmacologia , Linfócitos/efeitos dos fármacos , Vanadatos/farmacologia , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/genética , Cromossomos Humanos Par 2/genética , Sondas de DNA , Humanos , Hibridização in Situ Fluorescente , Interfase , Linfócitos/metabolismo , Masculino , Micronúcleos com Defeito Cromossômico/efeitos dos fármacos , Micronúcleos com Defeito Cromossômico/genética , Testes para Micronúcleos , Cromossomo X/genética
18.
Mutat Res ; 440(1): 35-43, 1999 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-10095127

RESUMO

Cytogenetic monitoring was carried out on a group of children from Gomel (Belarus), one of the areas most severely affected by radioactive contamination following the accident at the Chernobyl nuclear power plant, in 1986. We performed the micronucleus test (MN) in binucleated lymphocytes of 42 children (mean age: 11+/-2.34 years), 16 of whom were affected by thyroid gland tumor. Thirty healthy children living in Pisa (mean age: 14.96+/-2.17 years) were enrolled in the study as controls. Thyroid tumor affected children living in Gomel showed a statistically significant increase in the frequency of micronucleated cells as compared with the healthy children from Pisa. Moreover, a significant correlation was found between MN frequency and both the presence of tumor and higher 137Cs contamination. In addition, higher 137Cs contamination was more frequently observed in tumor affected children. These results suggest that the increased MN frequency is attributable more to 137Cs contamination rather than to the presence of the tumor itself.


Assuntos
Aberrações Cromossômicas , DNA de Neoplasias/efeitos da radiação , Linfócitos/efeitos da radiação , Micronúcleos com Defeito Cromossômico/efeitos da radiação , Neoplasias Induzidas por Radiação/sangue , Liberação Nociva de Radioativos , Neoplasias da Glândula Tireoide/sangue , Adolescente , Criança , Feminino , Humanos , Masculino , Testes para Micronúcleos , Neoplasias Induzidas por Radiação/genética , Centrais Elétricas , Radiação Ionizante , Cinza Radioativa , República de Belarus , Neoplasias da Glândula Tireoide/genética , Ucrânia
19.
Am J Med Genet ; 77(1): 12-5, 1998 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-9557886

RESUMO

Spondylocarpotarsal synostosis syndrome (SSS) or congenital synspondylism is a recently delineated clinical entity. At least 15 patients have been reported. We present 3 new patients, 2 of whom were sibs born to first-cousin parents. All of our patients had multiple synostoses involving cervical, thoracic and/or lumbar vertebral bodies and carpal/tarsal bones, scoliosis/lordosis, and short stature. Sensorineural deafness was found in 2 of the 3 patients. Analysis of clinical manifestations suggests clinical variability and genetic heterogeneity in SSS. Of a total of 18 SSS patients, 10 were five pairs of sibs from five families, with first-cousin consanguinity of parents in 3, indicating that at least one type of SS is an autosomal-recessive disorder.


Assuntos
Anormalidades Múltiplas/diagnóstico , Sinostose/diagnóstico , Anormalidades Múltiplas/genética , Ossos do Carpo/anormalidades , Ossos do Carpo/diagnóstico por imagem , Criança , Pré-Escolar , Feminino , Deformidades Congênitas da Mão/genética , Humanos , Linhagem , Radiografia , Escoliose/genética , Coluna Vertebral/anormalidades , Coluna Vertebral/diagnóstico por imagem , Síndrome , Sinostose/genética , Ossos do Tarso/anormalidades , Ossos do Tarso/diagnóstico por imagem
20.
Infez Med ; 5(4): 257-64, 1997 Dec.
Artigo em Italiano | MEDLINE | ID: mdl-12845315

RESUMO

The financial budget for public health care in Italy has been more and more restricted in the last few years, but, on the other hand, the care of AIDS patients is still very expensive and antibiotic therapy plays an important role in the management and cost of these patients. The antibiotic therapies and related costs have been evaluated in 99 patients affected by AIDS (59 pts), ARC (28 pts) or HIV serum positive (12 pts), all hospitalized or treated in Day Hospital for different bacterial infections in 1995 at the Department of Infectious Diseases, Ospedale Maggiore, Bologna, for a total of 7733 days of antibiotic therapy. The average cost for antibiotic therapy was about 400,000 Italian Lira, with no significant difference depending on the stage of HIV related disease. The crude cost for antibiotic treatment was not particularly high, but the high frequency of adverse events, registered in these patients, required additional medical support and/or a prolonged hospital stay, which increased substantially the total cost of management of bacterial infections.

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