RESUMO
Palmoplantar keratoderma-congenital alopecia (PPKCA) syndrome is a rare genodermatosis, with two clinically recognizable forms: dominant (Type 1) and recessive (Type 2). Reports of only 18 patients have been published to date, and the molecular basis of the condition is unknown. We describe two cases with PPKCA Type 2 (PPKCA2), comprising a novel patient, originally reported as an example of autosomal ichthyosis follicularis-atrichia-photophobia syndrome, and the 6-year follow-up of a previously published case. Extensive molecular studies of both patients excluded mutations in all the known genes associated with PPK and partially overlapping syndromes. The striking similarities between these two patients confirm PPKCA2 as a discrete genodermatosis, of which the main features are congenital and universal alopecia, diffuse keratosis pilaris, facial erythema, and a specific PPK with predominant involvement of the fingertips and borders of the hands and feet, with evolution of sclerodactyly, contractures and constrictions. Clinical follow-up of these patients has demonstrated progressive worsening of the hand involvement and attenuation of facial erythema.
Assuntos
Alopecia/diagnóstico , Alopecia/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Ictiose/diagnóstico , Ceratodermia Palmar e Plantar/genética , Fotofobia/diagnóstico , Adolescente , Alopecia/complicações , Alopecia/patologia , Diagnóstico Diferencial , Feminino , Dedos/patologia , Doenças Genéticas Ligadas ao Cromossomo X/complicações , Doenças Genéticas Ligadas ao Cromossomo X/patologia , Humanos , Ceratodermia Palmar e Plantar/complicações , Ceratodermia Palmar e Plantar/patologia , Doenças da Unha/genética , Doenças da Unha/patologiaRESUMO
Trichorhinophalangeal syndrome (TRPS) is a rare, autosomal dominant malformation syndrome characterized by hair, craniofacial and skeletal abnormalities, skin laxity, deformation of phalanges and anomalies of pelvis, femurs, and tibias. Three subtypes have been described: TRPS I, caused by mutations in TRPS1 gene on chromosome 8; TRPS II, a microdeletion syndrome affecting the TRPS1 and EXT1 genes; and TRPS III, a form with severe brachydactyly, due to short metacarpals, and severe short stature, but without exostoses. We present the case of a 7-year-old boy, affected by TRPS with a severe osteoporosis and several spontaneous bone fractures, an association described only once in the literature, successfully treated with biphosphonates. Bone mineral density (BMD) at dual-energy X-ray Absorptiometry (DXA) was of 0.331 g/cm(2) at lumbar spine with. He had four spontaneous femoral fractures in a year, and for this reason he was been operated for positioning intramedullary osteosynthesis and orthopedic supports. Due to the severity of the clinical and radiological pattern it was established, after approval of the Ethical Committee, to begin off-label therapy with infusions of neridronate at a dose of 2 mg/kg IV every 3 months. The treatment was, in this patient, effective both in terms of clinical (absence of new fractures) and mineralomethric (+45% BMD ath the lumbar level). We therefore suggest that treatment with biphosponates can be taken in account as a possible therapeutic option in case of bone fragility in patients with TRPSI.
Assuntos
Dedos/anormalidades , Doenças do Cabelo/diagnóstico , Síndrome de Langer-Giedion/diagnóstico , Nariz/anormalidades , Osteoporose/diagnóstico , Densidade Óssea , Conservadores da Densidade Óssea/uso terapêutico , Osso e Ossos/diagnóstico por imagem , Criança , Ácido Clodrônico/uso terapêutico , Análise Mutacional de DNA , Proteínas de Ligação a DNA/genética , Doenças do Cabelo/complicações , Doenças do Cabelo/genética , Humanos , Síndrome de Langer-Giedion/complicações , Síndrome de Langer-Giedion/genética , Masculino , Osteoporose/tratamento farmacológico , Osteoporose/etiologia , Fenótipo , Radiografia , Proteínas Repressoras , Fatores de Transcrição/genéticaRESUMO
Non-compaction of the left ventricle (NCLV) is a cardiomyopathy characterized by prominent left ventricular trabeculae and deep intertrabecular recesses. Associated extracardiac anomalies occur in 14-66% of patients of different series, while chromosomal anomalies were reported in sporadic cases. We investigated the prevalence of chromosomal imbalances in 25 syndromic patients with NCLV, using standard cytogenetic, subtelomeric fluorescent in situ hybridization, and array-comparative genomic hybridization (CGH) analyses. Standard chromosome analysis disclosed an abnormality in three (12%) patients, including a 45,X/46,XX mosaic, a 45,X/46,X,i(Y)(p11) mosaic, and a de novo Robertsonian 13;14 translocation in a child affected by hypomelanosis of Ito. Cryptic chromosome anomalies were found in six (24%) cases, including 1p36 deletion in two patients, 7p14.3p14.1 deletion, 18p subtelomeric deletion, 22q11.2 deletion associated with velo-cardio-facial syndrome, and distal 22q11.2 deletion, each in one case. These results recommend accurate clinical evaluation of patients with NCLV, and suggest that chromosome anomalies occur in about one third of syndromic NCLV individuals, without metabolic/neuromuscular disorder. Array-CGH analysis should be included in the diagnostic protocol of these patients, because different submicroscopic imbalances are causally associated with this disorder and can pinpoint candidate genes for this cardiomyopathy.
Assuntos
Cardiomiopatias/genética , Aberrações Cromossômicas , Ventrículos do Coração/patologia , Adolescente , Adulto , Cardiomiopatias/diagnóstico , Criança , Pré-Escolar , Hibridização Genômica Comparativa , Ecocardiografia Doppler , Eletrocardiografia , Feminino , Ventrículos do Coração/diagnóstico por imagem , Humanos , Hibridização in Situ Fluorescente , Lactente , Recém-Nascido , Cariótipo , Masculino , Síndrome , Adulto JovemAssuntos
Genes Recessivos , Ictiose Lamelar/genética , Lipase/genética , Mutação de Sentido Incorreto , Irmãos , Pré-Escolar , Feminino , Humanos , ItáliaRESUMO
Preharvest infections or conidia load on fruit surface by Penicillium digitatum, P. italicum, Alternaria citri and other filamentous fungi can cause important postharvest losses of citrus fruit. Reduction in pruning frequency occurred in the last decade together with un-picked yield that eventually rots on the trees have increased the risk of postharvest decay especially when environmental conditions at picking time are favourable to pathogens' development. Sanitation procedures in the packinghouses, alternate use of postharvest fungicides with different modes of action, along with fungicide application before harvest could be an effective approach to minimize postharvest decay in citrus fruit. The present study investigated the effectiveness of a preharvest treatment with pyrimethanil (PYR), a broad spectrum fungicide, recently registered in different citrus-producing countries for postharvest treatments of citrus fruit and widely used worldwide as a preharvest treatment to control various diseases in different crops. PYR (750 mg/L) was sprayed by a hand-back sprayer at run-off on 'Fremont' mandarins. The day after the treatment, half of the trees were sprayed with a 10(4) conidial suspension of P. digitatum at run-off. Fruit were harvested following 2 or 4 weeks from treatments. Sound or either wounded 2-mm-deep and 2-mm-wide or superficial wound-scratched fruit were stored at 20 degrees C and 90% RH and inspected for decay after 1, 2 or 3 weeks of storage. In fruit harvested after 2 weeks from field treatment, PYR remarkably reduced decay development during two weeks of storage in sound fruit and in wound-scratched fruit and was fairly effective even after 4 weeks from treatment, but was ineffective in fruit wounded 2 mm deep and 2 mm wide. PYR was also effective in reducing preharvest decay incited by P. digitatum, P. italicum and Botrytis cinerea, but not by other pathogens. Results show that preharvest treatment with PYR could be a feasible approach to reduce postharvest chemical control of decay of citrus fruit.
Assuntos
Citrus/microbiologia , Conservação de Alimentos/métodos , Frutas/microbiologia , Fungicidas Industriais/farmacologia , Doenças das Plantas/prevenção & controle , Pirimidinas/farmacologia , Citrus/crescimento & desenvolvimento , Armazenamento de Alimentos , Frutas/crescimento & desenvolvimento , Penicillium/efeitos dos fármacos , Penicillium/crescimento & desenvolvimento , Doenças das Plantas/microbiologia , Esporos Fúngicos/efeitos dos fármacos , Esporos Fúngicos/crescimento & desenvolvimentoRESUMO
Green and blue molds, respectively caused by Penicillium digitatum Sacc., and P. italicum Wehmer, are the most important postharvest diseases of citrus fruit Postharvest management of these pathogens is mainly based on the application of thiabendazole (TBZ) or imazalil (IMZ) fungicides. However, their intensive and prolonged use has led to the selection of TBZ- IMZ-resistant strains of these pathogens and to a reduction of TBZ and IMZ effectiveness to control postharvest decay. However, while TBZ may become completely ineffective against TBZ-resistant strains of P. digitatum, reduction of IMZ efficacy is only partial, and an effective control of decay can still be achieved by increasing its concentration, heating the treatment-solution and/or combining IMZ with sodium bicarbonate (SBC) or other food additives or natural salts. In this study, 'Desiderio' and 'Nova' mandarins were inoculated with spores of a sensitive strain of P. digitatum to IMZ and TBZ (PDs) or with a strain of P. digitatum with double resistance to both fungicides (PDr) and immersed in IMZ or TBZ emulsions at increasing concentrations up to 1000 mg/L or in IMZ (25, 200 or 400 mg/L), SBC (0.5, 1 or 2%) or IMZ + SBC emulsions either at 20 or 40 degrees C. IMZ was superior to TBZ to control decay of 'Desiderio' mandarins incited by PDs and was also effective to control decay in fruit inoculated with PDr, while TBZ even at the highest rate was completely ineffective. In 'Desiderio' mandarins inoculated with PDs, a complete control of decay was achieved with 25 mg/L IMZ but in fruit inoculated with PDr, 25 mg/L IMZ were ineffective to control decay despite in combination with SBC at 2% a synergistic effect was detected. In contrast, a good control of decay was achieved with 400 mg/L IMZ. In 'Nova' mandarins after 1 week of incubation at 20 degrees C decay incidence in fruit dipped in 400 mg/L at 20 degrees C or 200 mg/L IMZ at 40 degrees C was almost completely inhibited, while the addition of SBC at 0.5, 1 or 2% did not improve treatments performance in fruit inoculated with PDs. However, when 'Nova' mandarins were inoculated with PDr, SBC showed a modest but significant control of decay and in combination with IMZ either at 400 mg/L and 20 degrees C or 200 mg/L and 40 degrees C, significantly improved decay control. SBC did not affect IMZ residue load in 'Valencia' oranges, whereas dipping the fruit in 400 mg/L IMZ at 20 degrees C produced similar IMZ residue load as dips at 200 mg/L IMZ at 40 degrees C. In all cases, residue levels of IMZ never exceeded 2 mg/kg, which is about 40% of the maximum residue limits (MRLs) allowed in European countries. Thus, despite the selection of IMZ-resistant strains of P. digitatum, IMZ continues to be highly effective to control green mold of citrus fruit at concentrations leaving on fruit surface residue levels below the MRLs.
Assuntos
Resíduos de Drogas/análise , Conservação de Alimentos/métodos , Fungicidas Industriais/análise , Fungicidas Industriais/farmacologia , Imidazóis/farmacologia , Penicillium/efeitos dos fármacos , Bicarbonato de Sódio/análise , Bicarbonato de Sódio/farmacologia , Citrus/química , Citrus/microbiologia , Farmacorresistência Fúngica , Frutas/química , Frutas/microbiologia , Temperatura Alta , Imidazóis/análise , Penicillium/crescimento & desenvolvimentoRESUMO
Ring 17 syndrome is a rare disorder with clinical features influenced by the presence or deletion of the Miller-Dieker critical region (MDCR). Presence of the MDCR is associated with a mild phenotype, including growth delay (GD), mental retardation (MR), seizures, cafè au lait skin (CALS) spots and minor facial dysmorphisms. Previous studies have been mainly focused on this locus providing poor information about the role of other genes located on the p- and q-arms. Here, we used bacterial artificial chromosome (BAC)/P1 artificial chromosome (PAC) and fosmid clones as fluorescence in situ hybridization (FISH) probes to perform a cyto-molecular analysis of a ring 17 case and found that the breakpoints were close to the telomeric ends. METRNL is the sole gene located on the q-arm terminal end, whereas two open reading frames and the RPH3AL gene are located on the terminal p-arm. To detect possibly unrevealed small deletions involving the transcription units, we used subcloned FISH probes obtained by long-range polymerase chain reaction (PCR), which showed that the investigated regions were preserved. Comparing our findings with other reports, it emerges that different breakpoints, involving (or not) large genomic deletions, present overlapping clinical aspects. In conclusion, our data suggest that a mechanism based on gene expression control besides haploinsufficiency should be considered to explain the common phenotypic features found in the mild ring 17 syndrome.
Assuntos
Anormalidades Múltiplas/genética , Anormalidades Múltiplas/patologia , Quebra Cromossômica , Cromossomos Humanos Par 17/genética , Cromossomos em Anel , Adolescente , Adulto , Criança , Pré-Escolar , Fácies , Feminino , Humanos , Hibridização in Situ Fluorescente , Lactente , Recém-Nascido , Cariotipagem , Masculino , Fenótipo , Mapeamento Físico do Cromossomo , SíndromeRESUMO
Cytogenetic analyses of constitutional diseases have disclosed several chromosomal rearrangements. At the molecular level, these rearrangements often result in the breakage of genes or alteration of genome architecture. Fluorescence in situ hybridization (FISH) and molecular investigations of a patient showing hypotonia and dysmorphic traits revealed a masked complex chromosome abnormality previously detected by G-banding as a simple 8qter deletion. To characterize the genetic rearrangements panels of bacterial artificial chromosomes (BACs) covering 8q24.22-->qter were constructed, and short tandem repeats (STRs) were used to refine the localization of the breakpoints and to assess the parental origin of the defect. Chromosome 8 displayed the breakpoint at 8q24.22 and an unexpected distal breakpoint at 8q24.23 resulting in unbalanced translocation of a small 8q genomic region on the chromosome 16qter. The study of the 16qter region revealed that the 16q subtelomere was retained and the translocated material of distal 8q was juxtaposed. Moreover, molecular analyses showed that part of the translocated 8qter segment on der(16) was partially duplicated, inverted and that the rearrangement arose in the paternal meiosis. These findings emphasize the complexity of some only apparently simple chromosomal rearrangements and suggest a subtelomeric FISH approach to enhance diagnostic care when a cytogenetic terminal deletion is found.
Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 8 , Sequência de Bases , Bandeamento Cromossômico , Primers do DNA , Humanos , Hibridização in Situ Fluorescente , LactenteRESUMO
Dopamine-agonist cabergoline (CB) reduces prolactin (PRL) secretion and tumor size in 80% of patients with prolactin-secreting adenomas (PRL-omas) by binding type 2 dopamine receptor (DRD2). The mechanisms responsible for resistance to CB remain largely unknown. To assess the association of DRD2 with sensitivity to CB, TaqI-A1/A2, TaqI-B1/B2, HphI-G/T and NcoI-C/T genotypes were determined in a cross-sectional retrospective study, including 203 patients with PRL-oma. DRD2 alleles frequencies did not differ between patients and 212 healthy subjects. Conversely, NcoI-T allele frequency was higher in resistant rather than responsive patients, considering both PRL normalization (56.6 vs 45.3%, P=0.038) and tumor shrinkage (70.4 vs 41.4%, P=0.006). Finally, [TaqI A1-/TaqI B1-/HphI T-/NcoI T-] haplotype was found in 34.5% of patients normalizing PRL with < or =3 mg/week of CB vs 11.3% of resistants (P=0.021). In conclusion, resistance to CB was associated with DRD2 NcoI-T+ allele, consistent with evidence suggesting that this variant may lead to reduction and instability of DRD2 mRNA or protein.
Assuntos
Adenoma/tratamento farmacológico , Agonistas de Dopamina/uso terapêutico , Ergolinas/uso terapêutico , Neoplasias Hipofisárias/tratamento farmacológico , Polimorfismo Genético , Prolactina/metabolismo , Receptores de Dopamina D2/genética , Adenoma/genética , Adenoma/metabolismo , Adulto , Alelos , Cabergolina , Estudos Transversais , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/metabolismo , Estudos RetrospectivosRESUMO
Non-classic Cystic Fibrosis (CF) still represents a difficult entity to diagnose. We present a case of two sisters affected by mild pulmonary symptoms started at puberty, carriers of the F508del mutation associated with the T5TG13 combination. We discuss the clinical utility of TG repeat testing in individuals carrying the T5 variant. Furthermore, this case-report leads to reflect on the natural history of CF and the correct management of its atypical forms.
Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística/diagnóstico , Fibrose Cística/genética , Bronquiectasia/etiologia , Fibrose Cística/complicações , Feminino , Triagem de Portadores Genéticos , Humanos , Mutação , Linhagem , Adulto JovemRESUMO
Pome trees, apple, pear, and quince, are classified into the subfamily Pomoideae, belonging to the Rosaceae family. Their autumnal fruits are consumed worldwide in different forms, that is, fresh or transformed into jams, jelly, juices, etc. Their well-established beneficial properties to human health were found mainly related to their phenolic content. Pulp and peel aqueous acetone extracts obtained from Tunisian fruits at commercial maturity were comparatively evaluated for their phenolic profiles and antioxidant and antimicrobial potentials. The phenolic compounds present in the extracts were identified and quantified using RP-HPLC-DAD and ESI-MS techniques. Significant differences in the chromatographic profiles among these fruits, as well as between pulp and peel extracts of each fruit, were observed. Quince, followed by 'Red Delicious', peel extracts showed the highest phenolic content (160.33 and 110.90 mg/100 g of fresh weight). The stronger inhibitory effect on DPPH radicals corresponded to those obtained from peel materials. A comparative analysis of the antimicrobial potential against a range of microorganism strains was also carried out. Staphylococcus aureus, Pseudomonas aeruginosa, and Bacillus cereus were the most sensitive to the active extracts. Among the examined phenolic extracts, 'Red Delicious' and quince peels showed the highest effects for inhibiting bacteria growth. Minimum inhibitory and bactericide concentrations ranged from 10(2) to 10(4) microg of polyphenol/mL. Red skin apple and quince peels could be of great interest as important antioxidant and antimicrobial polyphenol sources.
Assuntos
Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Flavonoides/análise , Frutas/química , Fenóis/análise , Extratos Vegetais/química , Acetona , Cromatografia Líquida de Alta Pressão , Malus/química , Polifenóis , Pyrus/química , Rosaceae/química , Espectrometria de Massas por Ionização por Electrospray , TunísiaRESUMO
The interaction of ochratoxin A (OTA) and 20 yeast strains of Saccharomyces cerevisiae and Kloeckera apiculata during alcoholic fermentation was studied. Levels of OTA were determined in the fermentation liquid and in the yeast cells solid using a high-performance liquid chromatography system with a fluorescence detector. Yeast cells do not adsorb OTA, and for all yeasts, OTA levels did not affect the alcoholic fermentation. Some yeast strains reduced levels of OTA, whereas other strains did not show any effect demonstrating that OTA level reduction is not a genus species characteristic but a strain trait.
Assuntos
Ascomicetos/metabolismo , Carcinógenos/análise , Ocratoxinas/análise , Saccharomyces cerevisiae/metabolismo , Absorção , Ascomicetos/química , Fermentação , Saccharomyces cerevisiae/química , Vinho/microbiologiaRESUMO
Wilms' tumor (WT) is caused by abnormal development of embryonal kidney cells. WT cells are frequently affected by deletions or functional inactivation of maternal alleles at chromosome 11p15, which indicates that the loss of maternally expressed genes in this region plays an important role in WT pathogenesis. Maternally expressed genes indeed exist within an imprinted region at 11p15.5. Among these, BWR1C is highly expressed in fetal but not in adult kidney, which suggests that it may fulfil an important role in kidney development. Here, we demonstrate that the lack of BWR1C expression is common in WT. Its homology with the proapoptotic gene TDAG51 suggests that the loss of BWR1C expression may be relevant in WT development. In addition, the analysis of the expression of other 11p15 imprinted genes and kidney-developmentally regulated genes indicates that IGF2 overexpression, inappropriate coexpression of RET and GDNF and, in some cases, down-regulation of CDKN1C may also play an important role in the pathogenesis of WT. Our results add new elements to the understanding of the biological basis of WT, which may have implications for WT diagnosis and therapy.
Assuntos
Cromossomos Humanos Par 11/genética , Proteínas de Drosophila , Impressão Genômica , Neoplasias Renais/genética , Rim/metabolismo , Fatores de Crescimento Neural , Proteínas de Transporte de Cátions Orgânicos , RNA/genética , Tumor de Wilms/genética , Adulto , Caderinas/genética , Inibidor de Quinase Dependente de Ciclina p57 , Proteínas de Ligação a DNA/genética , Feminino , Feto , Regulação da Expressão Gênica no Desenvolvimento , Regulação Neoplásica da Expressão Gênica , Fator Neurotrófico Derivado de Linhagem de Célula Glial , Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial , Humanos , Rim/embriologia , Proteínas do Tecido Nervoso/genética , Moléculas de Adesão de Célula Nervosa/genética , Proteínas Nucleares/genética , Fator de Transcrição PAX2 , Proteínas/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-ret , Receptores Proteína Tirosina Quinases/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Transcrição/genética , Células Tumorais Cultivadas , Proteínas WT1RESUMO
In this article we report a case of a 7-year-old boy affected by acute lymphoblastic leukemia of the common type. Bone marrow examination at diagnosis showed a reciprocal translocation between the long arm of chromosome 3 and the long arm of chromosome 12. This previously unpublished translocation is discussed and compared to the findings in the current literature.
Assuntos
Cromossomos Humanos Par 12 , Cromossomos Humanos Par 3 , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Translocação Genética , Criança , Humanos , MasculinoRESUMO
Trisomy 8 is a relatively common finding in acute nonlymphoblastic leukemia (ANLL). In childhood acute lymphoblastic leukemia (ALL) it apparently is much more rare. Although Human Gene Mapping 11 included trisomy 8 as a marker for a subgroup of ALL, morphologic and immunologic characteristics of this entity have not been defined. We describe a case of early T-cell ALL (T-ALL) in a pediatric patient in whom this abnormality was the sole chromosome aberration. In situ hybridization with a chromosome 8-specific alpha-satellite DNA probe was performed. Our data are discussed and compared with pertinent literature.
Assuntos
Cromossomos Humanos Par 8 , Leucemia-Linfoma de Células T do Adulto/genética , Trissomia , Pré-Escolar , Feminino , Humanos , Imunofenotipagem , Hibridização in Situ FluorescenteRESUMO
The ALL1 gene at 11q23 is a promiscuous gene participating in chromosomal abnormalities of acute leukemias with 1 of over 30 potential partner genes. Among these, the AF10 gene at band 10p12 has been recently cloned and characterized. Acute leukemias with the ALL1/AF10 chimeric gene frequently show heterogeneity in the breakpoints on 10p, as well as complex insertion (10;11) as a result of complex molecular mechanisms leading to the ALL1/AF10 fusion. In this context, we report the first description of an infant acute lymphoblastic leukemia with an interstitial insertion of the AF10 gene into the 11q23 band, resulting in the transcription of the ALL1/AF10 fusion product. Furthermore, we show how different diagnostic tools such as molecular, cytogenetic, and fluorescence in situ hybridization (FISH) analyses should be combined to resolve complex situations in the 11q23 setting.
Assuntos
Cromossomos Humanos Par 10/genética , Cromossomos Humanos Par 12/genética , Proteínas de Ligação a DNA/genética , Proteínas de Fusão Oncogênica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proto-Oncogenes , Fatores de Transcrição/genética , Translocação Genética/genética , Proteínas de Ligação a DNA/análise , Feminino , Histona-Lisina N-Metiltransferase , Humanos , Hibridização in Situ Fluorescente , Recém-Nascido , Proteína de Leucina Linfoide-Mieloide , Proteínas de Fusão Oncogênica/análise , Fatores de Transcrição/análiseRESUMO
Simultaneous comparative assessment of tumor contamination in bone marrow aspirates and peripheral blood stem cell collections using immunocytochemical techniques was done in 6 children with neuroectodermal tumors. In 3 neuroblastoma patients tumor cells were detected in 5 of 16 marrow samples but not in peripheral blood stem cells. Clonogenic tumor cell reinfusion in the autologous support setting may be avoided in neuroblastoma patients by using peripheral blood stem cells.
Assuntos
Coleta de Amostras Sanguíneas , Medula Óssea/patologia , Neoplasias Cerebelares/patologia , Células-Tronco Hematopoéticas/patologia , Meduloblastoma/patologia , Neuroblastoma/patologia , Adolescente , Neoplasias Cerebelares/sangue , Criança , Pré-Escolar , Humanos , Meduloblastoma/sangue , Invasividade Neoplásica , Neuroblastoma/sangueRESUMO
A method for collecting peripheral blood mononuclear cells following mobilizing chemotherapy in pediatric patients is described. The critical elements of the method included temporary heparinization of the patient to reduce citrate overload, and limiting extracorporeal circulation to 15% of the patient's blood volume using packed red blood cells and albumin. A median of 0.9 x 10(8) mononuclear cells/kg per collection were harvested in 40 collections from eight patients with only one episode of fever and chills. Peripheral blood stem cells were reinfused into six of these patients with refractory/recurrent pediatric tumors after intensive chemotherapy. Bone marrow reconstitution followed with a mean of 30 days (19-38) for absolute neutrophils and 48 days (32-275+) for platelets. Previous chemotherapy did not appear to affect peripheral blood stem cell efficacy in reconstituting chemotherapy-ablated bone marrow.
Assuntos
Coleta de Amostras Sanguíneas/métodos , Medula Óssea/patologia , Transplante de Células-Tronco Hematopoéticas , Leucopenia/terapia , Adolescente , Criança , Pré-Escolar , Estudos de Viabilidade , Humanos , Leucopenia/induzido quimicamente , Neutropenia/induzido quimicamente , Neutropenia/terapia , Terapia de Salvação/métodosRESUMO
Thirteen patients with Stage III (3 patients) or Stage IV (10 patients) neuroblastoma were treated with a new iron chelation-cytotoxic therapy regimen. Deferoxamine given for five consecutive days followed by 3 days of cyclophosphamide, etoposide, carboplatin, and thiotepa (D-CECaT) caused moderate to severe myelotoxicity. In 39 courses there were four episodes of sepsis; platelet and packed red blood cell transfusions were required in 72% and 82% of courses, respectively. Mild nausea and vomiting occurred in 52% of courses. Objective responses after two courses were observed in 12 of 13 patients. Three of four partial responses were achieved in previously treated relapsed patients, and seven of eight complete responses (four of which were surgically documented) were achieved in previously untreated patients. This cytoreduction regimen appears to be an improvement over other initial induction regimens and may be worth testing in larger populations.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia por Quelação , Neuroblastoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Doenças da Medula Óssea/induzido quimicamente , Carboplatina/administração & dosagem , Criança , Pré-Escolar , Ciclofosfamida/administração & dosagem , Desferroxamina/administração & dosagem , Etoposídeo/administração & dosagem , Humanos , Lactente , Projetos Piloto , Indução de Remissão , Tiotepa/administração & dosagemRESUMO
In this review the results obtained in the 1990s from research on the behavior of pesticide residues on grapes, from treatment to harvest, and their fate in drying, wine-making, and alcoholic beverage processing are reported. The fungicide residues on grapes (cyproconazole, hexaconazole, kresoxim-methyl, myclobutanil, penconazole, tetraconazole, and triadimenol), the application rates of which were of a few tens of grams per hectare, were very low after treatment and were not detectable at harvest. Pyrimethanil residues were constant up to harvest, whereas fluazinam, cyprodinil, mepanipyrim, azoxystrobin, and fludioxonil showed different disappearance rates (t(1/2) = 4.3, 12, 12.8, 15.2, and 24 days, respectively). The decay rate of the organophosphorus insecticides was very fast with t(1/2) ranging between 0.97 and 3.84 days. The drying process determined a fruit concentration of 4 times. Despite this, the residue levels of benalaxyl, phosalone, metalaxyl, and procymidone on sun-dried grapes equalled those on the fresh grape, whereas they were higher for iprodione (1.6 times) and lower for vinclozolin and dimethoate (one-third and one-fifth, respectively). In the oven-drying process, benalaxyl, metalaxyl, and vinclozolin showed the same residue value in the fresh and dried fruit, whereas iprodione and procymidone resides were lower in raisins than in the fresh fruit. The wine-making process begins with the pressing of grapes. From this moment onward, because the pesticide on the grape surface comes into contact with the must, it is in a biphasic system, made up of a liquid phase (the must) and a solid phase (cake and lees), and will be apportioned between the two phases. The new fungicides have shown no effect on alcoholic or malolactic fermentation. In some cases the presence of pesticides has also stimulated the yeasts, especially Kloeckera apiculata, to produce more alcohol. After fermentation, pesticide residues in wine were always smaller than those on the grapes and in the must, except for those pesticides that did not have a preferential partition between liquid and solid phase (azoxystrobin, dimethoate, and pyrimethanil) and were present in wine at the same concentration as on the grapes. In some cases (mepanipyrim, fluazinam, and chlorpyrifos) no detectable residues were found in the wines at the end of fermentation. From a comparison of residues in wine obtained by vinification with and without skins, it can be seen that their values were generally not different. Among the clarifying substances commonly used in wine (bentonite, charcoal, gelatin, polyvinylpolypyrrolidone, potassium caseinate, and colloidal silicon dioxide), charcoal allowed the complete elimination of most pesticides, especially at low levels, whereas the other clarifying substances were ineffective. Wine and its byproducts (cake and lees) are used in the industry to produce alcohol and alcoholic beverages. Fenthion, quinalphos, and vinclozolin pass into the distillate from the lees only if present at very high concentrations, but with a very low transfer percantage (2, 1, and 0.1%, respectively). No residue passed from the cake into the distillate, whereas fenthion and vinclozolin pass from the wine, but only at low transfer percentages (13 and 5%, respectively).