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1.
Biomed Pharmacother ; 179: 117284, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39151310

RESUMO

Osteosarcoma is the most common primary bone malignancy with a challenging prognosis marked by a high rate of metastasis. The limited success of current treatments may be partially attributed to an incomplete understanding of osteosarcoma pathophysiology and to the absence of reliable in vitro models to select the best molecules for in vivo studies. Among the natural compounds relevant for osteosarcoma treatment, Licochalcone A (Lic-A) and chalcone derivatives are particularly interesting. Here, Lic-A and selected derivatives have been evaluated for their anticancer effect on multicellular tumor spheroids from MG63 and 143B osteosarcoma cell lines. A metabolic activity assay revealed Lic-A, 1i, and 1k derivatives as the most promising candidates. To delve into their mechanism of action, caspase activity assay was conducted in 2D and 3D in vitro models. Notably, apoptosis and autophagic induction was generally observed for Lic-A and 1k. The invasion assay demonstrated that Lic-A and 1k possess the ability to mitigate the spread of osteosarcoma cells within a matrix. The effectiveness of chalcone as a natural scaffold for generating potential antiproliferative agents against osteosarcoma has been demonstrated. In particular, chalcones exert their antiproliferative activity by inducing apoptosis and autophagy, and in addition they are capable of reducing cell invasion. These findings suggest Lic-A and 1k as promising antitumor agents against osteosarcoma cells.

2.
Pediatr Surg Int ; 39(1): 247, 2023 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-37584865

RESUMO

PURPOSE: Urological management of Cloacal Malformation (CM) focuses on preserving renal function and continence. Study aim was to analyze urinary and intestinal outcomes in CM patients, considering the length of common channel (CC) and presence of occult spinal dysraphism (OSD). METHODS: Retrospective review of CM treated at our institution by a multidisciplinary team from 1999 to 2020. Patients with follow-up < 2.5 years were excluded. Length of CC, renal function, urinary and bowel outcomes, presence of associated anomalies (especially OSD) were evaluated. RESULTS: Twenty patients were included, median age at follow-up: 8 years (4-15). A long CC > 3 cm was described in 11 (55%). Chronic kidney disease was found in 3 patients. Urinary continence was achieved in 8/20 patients, dryness (with intermittent catheterization) in 9/20. Fecal continence was obtained in 3/20, cleanliness in 14 (under bowel regimen). OSD was present in 10 patients (higher prevalence in long-CC, 73%). Among OSD, 1 patient reached fecal continence, 7 were clean; 2 achieved urinary continence, while 6 were dry. CONCLUSIONS: Length of CC and OSD may affect urinary and fecal continence. An early counseling can improve outcome at long-term follow-up. Multidisciplinary management with patient centralization in high grade institutions is recommended to achieve better results.


Assuntos
Defeitos do Tubo Neural , Incontinência Urinária , Humanos , Animais , Pré-Escolar , Criança , Adolescente , Cloaca/anormalidades , Intestino Grosso , Urodinâmica , Estudos Retrospectivos
3.
Sci Rep ; 9(1): 11172, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31371758

RESUMO

The increasing demands from micro-power applications call for the development of the electrode materials for Li-ion microbatteries using thin-film technology. Porous Olivine-type LiFePO4 (LFP) and NASICON-type Li3Fe2(PO4)3 have been successfully fabricated by radio frequency (RF) sputtering and post-annealing treatments of LFP thin films. The microstructures of the LFP films were characterized by X-ray diffraction and scanning electron microscopy. The electrochemical performances of the LFP films were evaluated by cyclic voltammetry and galvanostatic charge-discharge measurements. The deposited and annealed thin film electrodes were tested as cathodes for Li-ion microbatteries. It was found that the electrochemical performance of the deposited films depends strongly on the annealing temperature. The films annealed at 500 °C showed an operating voltage of the porous LFP film about 3.45 V vs. Li/Li+ with an areal capacity of 17.9 µAh cm-2 µm-1 at C/5 rate after 100 cycles. Porous NASICON-type Li3Fe2(PO4)3 obtained after annealing at 700 °C delivers the most stable capacity of 22.1 µAh cm-2 µm-1 over 100 cycles at C/5 rate, with an operating voltage of 2.8 V vs. Li/Li+. The post-annealing treatment of sputtered LFP at 700 °C showed a drastic increase in the electrochemical reactivity of the thin film cathodes vs. Li+, leading to areal capacity ~9 times higher than as-deposited film (~27 vs. ~3 µAh cm-2 µm-1) at C/10 rate.

4.
Breast Cancer Res Treat ; 132(3): 1063-72, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22200869

RESUMO

In preclinical models, the histone deacetylase inhibitor vorinostat sensitizes breast cancer cells to tubulin-polymerizing agents and to anti-vascular endothelial growth factor-directed therapies. We sought to determine the safety and efficacy of vorinostat plus paclitaxel and bevacizumab as first-line therapy in metastatic breast cancer (MBC), and the biological effects of vorinostat in vivo. For this purpose of this study, 54 patients with measurable disease and no prior chemotherapy for MBC received vorinostat (200 or 300 mg PO BID) on days 1-3, 8-10, and 15-17, plus paclitaxel (90 mg/m(2)) on days 2, 9, 16, and bevacizumab (10 mg/kg) on days 2 and 16 every 28 days. The primary objective of the phase I study was to determine the recommended phase II dose (RPTD) of vorinostat, and for the phase II to detect an improvement of response rate from 40 to 60% (alpha = 0.10, beta = 0.10). No dose limiting toxicities were observed, and the RPTD of vorinostat was 300 mg BID. For the primary efficacy analysis in 44 patients at the RPTD, we observed 24 objective responses (55%, 95% confidence intervals (C.I) 39%, 70%). The adverse event profile was consistent with paclitaxel-bevacizumab, with the exception of increased diarrhea with the addition of vorinostat. Analysis of serial tumor biopsies in seven patients showed increased acetylation of Hsp90 and α-tubulin following vorinostat. Vorinostat induces histone and alpha tubulin acetylation and functional inhibition of Hsp90 in breast cancer in vivo and can be safely combined with paclitaxel and bevacizumab.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/secundário , Tubulina (Proteína)/metabolismo , Acetilação , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Bevacizumab , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Feminino , Proteínas de Choque Térmico HSP90/metabolismo , Humanos , Ácidos Hidroxâmicos/administração & dosagem , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Resultado do Tratamento , Vorinostat
5.
Radiol Med ; 117(2): 201-13, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22020434

RESUMO

PURPOSE: Complications correlated with percutaneous radiofrequency ablation (RFA) and microwave ablation (MWA) of lung tumours were retrospectively reviewed to compare them with data from the literature and to assess risk factors related with the procedures. MATERIALS AND METHODS: From January 2003 to January 2009, 29 patients (36 lung lesions) were treated with RFA; from January 2007 to January 2009, 16 patients (17 lung lesions) were treated with MWA. Complications recorded at our institution are reported following the Society of Interventional Radiology guidelines. A systematic review of the literature was performed. RESULTS: Any major complication of RFA or MWA was recorded. In agreement with the literature, pneumothorax was the most frequent complication, even though the incidence in our series was lower than reported in the literature (3.5% vs. 4.3-18%). Other complications of RFA were pleural effusion and subcutaneous emphysema. No massive haemorrhages, haemoptysis, abscesses, pneumonia, infections or tumour seeding were recorded in our series. The most common complication of MWA was pneumothorax (25% vs. 39% reported in the literature). Pleural effusion was a common reaction, but therapeutic drainage was never required. CONCLUSIONS: Pneumothorax is the most common complication of both techniques. RFA and MWA are both excellent choices in terms of safety and tolerance.


Assuntos
Ablação por Cateter/métodos , Neoplasias Pulmonares/cirurgia , Micro-Ondas/uso terapêutico , Complicações Pós-Operatórias/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Itália/epidemiologia , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Radiografia Torácica , Estudos Retrospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X
6.
Radiol Med ; 114(4): 608-25, 2009 Jun.
Artigo em Inglês, Italiano | MEDLINE | ID: mdl-19444588

RESUMO

PURPOSE: The treatment of pain in bone metastases is currently multidisciplinary. Among the various therapies, local radiotherapy is the gold standard for pain palliation from single metastasis, even though the maximum benefit is obtained between 12 and 20 weeks from initiation. In carefully selected patients, several ablation therapies achieve this objective in 4 weeks. The purpose of this study was to assess the technical success, effectiveness and possible complications of percutaneous ablation therapies in patients with symptomatic bone metastases. MATERIALS AND METHODS: From November 2003 to May 2008, ten ablation treatments were performed in ten patients with acute pain from metastatic bone lesions. Patient selection and choice of the most appropriate ablation treatment was made based on lesion characteristics. Three patients were treated with radiofrequency, one with plasma-mediated radiofrequency, two with plasma-mediated radiofrequency and cementoplasty, three with radiofrequency and cementoplasty and one with microwave. RESULTS: Assessments were based not only on imaging but also on the visual analogue scale (VAS) score for determining pain and on changes in morphine-equivalent doses. In both cases, 3-month follow-up showed a statistically significant reduction of pain. In no case did local complications occur either during or after treatment. Only one patient treated with radiofrequency (1/9, 11%) developed low-grade fever and general malaise during the 6 days following the procedure, compatible with a post-radiofrequency syndrome, which was treated with acetaminophen (paracetamol) only and resolved on day 7. CONCLUSIONS: Percutaneous ablation therapies represent a safe and valuable alternative for treating localised pain from single bone metastasis, providing rapid (4-week) relief of symptoms and a significant reduction in morphine doses. This contributes to improving the quality of life of patients with metastatic disease.


Assuntos
Neoplasias Ósseas/secundário , Neoplasias Ósseas/cirurgia , Ablação por Cateter , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgésicos Opioides/uso terapêutico , Neoplasias Ósseas/complicações , Neoplasias Ósseas/tratamento farmacológico , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Morfina/uso terapêutico , Dor/tratamento farmacológico , Dor/etiologia , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento
7.
Transplant Proc ; 40(6): 1986-8, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18675108

RESUMO

The aim of this study was to compare the incidence of ventilator-associated pneumonia (VAP) and clinical outcome among patients undergoing orthotopic liver transplantation (OLT) admitted to our surgical intensive care unit (ICU). Patients with an ICU stay longer than 4 days who had undergone surgery within 48 hours of admission were included in the study. Patients were subdivided into a liver transplant group (OLT) and no-liver transplant group (noLT). Diagnosis of VAP was based on microbiological data with a positive culture from a sample collected >or=48 hours after admission. VAP was defined as early if the positive culture occurred within the 4th day of admission, and late if after the 4th day. Three hundred seventy-three noLT and 71 OLT patients showed no differences in sex, mean severity score on admission (SAPS II), length of stay, and outcomes. The incidence of VAP was also similar in the 2 groups (27.3% in the noLT group vs 25.3% in the OLT group). Both in the OLT and noLT groups, the VAP patients showed higher (P< .05) SAPS II scores on admission, length of ICU stay, and mortality rates than the non-VAP patients, without any difference between the 2 groups. VAP is a frequent complication in ICU surgical patients, particularly those with high severity scores on admission. In an ICU surgical population, liver transplantation per se does not seem to increase the patients' risk either for VAP acquisition or for bad outcomes.


Assuntos
Transplante de Fígado/efeitos adversos , Pneumonia Associada à Ventilação Mecânica/epidemiologia , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Humanos , Incidência , Unidades de Terapia Intensiva , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento
8.
J Vet Intern Med ; 22(4): 976-84, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18564221

RESUMO

BACKGROUND: The occurrence of spontaneous tumors in pet animals has been estimated in a few European and North American veterinary cancer registries with dissimilar methodologies and variable reference populations. OBJECTIVES: The Animal Tumor Registry (ATR) of Genoa, Italy, was established in 1985 with the aim of estimating the occurrence of spontaneous tumors in dogs. METHODS: Six thousand seven hundred and forty-three tumor biopsy specimens were received from local veterinarians in the Municipality of Genoa between 1985 and 2002. Three thousand and three hundred and three (48.9%) biopsy specimen samples were diagnosed as cancer and were coded according to the International Statistical Classification of Diseases (ICD-9). RESULTS: Mammary cancer was the most frequently diagnosed cancer in female dogs, accounting for 70% of all cancer cases. Incidence of all cancers was 99.3 per 100,000 dog-years (95% CI: 93.6-105.1) in male dogs and 272.1 (95% CI: 260.7-283.6) in female dogs. The highest incidence rates were detected for mammary cancer (IR = 191.8, 95% CI: 182.2-201.4) and for non-Hodgkin's lymphoma (IR = 22.9, 95% CI: 19.7-26.5) in bitches and for non-Hodgkin's lymphoma (IR = 19.9, 95% CI: 17.4-22.7) and skin cancer (IR = 19.1, 95% CI: 16.6-21.8) in male dogs. All cancer IR increased with age ranging between 23.7 (95% CI: 18.4-30.1) and 763.2 (95% CI: 700.4-830.1) in bitches and between 16.5 (95% CI: 12.8-21.1) and 237.6 (95% CI: 209.1-269.0) in male dogs aged < or =3 years and >9-11 years. CONCLUSION: This study summarizes the work done by the ATR of Genoa, Italy, between 1985 and 2002. All cancer incidence was 3 times higher in female than in male dogs, a difference explained by the high rate of mammary cancer observed in bitches. Because a biopsy specimen was required to make a cancer diagnosis, cancer rates for internal organs cancers, such as respiratory and digestive tract cancers may have been underestimated in the study population.


Assuntos
Doenças do Cão/epidemiologia , Neoplasias/veterinária , Animais , Animais Domésticos , Bases de Dados Factuais , Cães , Feminino , Incidência , Itália/epidemiologia , Masculino , Neoplasias/epidemiologia , Caracteres Sexuais , Fatores de Tempo
9.
Vet Res Commun ; 31(2): 173-84, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17186410

RESUMO

We describe the expression of pStat3-ser727 (signal transducer and activator of transcription 3 phosphorylated on serine 727) in normal, hyperplastic and neoplastic feline mammary gland tissue assessed by immunohistochemistry in 56 cats. The samples included 4 normal mammary non-lactating tissues, 13 hyperplastic lesions (9 lobular and 4 fibroepithelial) and 39 tumours (6 benign and 33 carcinomas). For immunohistochemistry, tissue sections were incubated with anti-pStat3-ser727 monoclonal antibodies and visualized with EnVision-DAB polymer. pStat3-ser727 positivity was quantified in a semi-quantitative manner, differentiating cytoplasmic and nuclear localization. Intense anti-pStat3-ser727 immunoreactivity was detected in epithelial neoplastic cells and in the fibro-component in two fibroepithelial hyperplastic lesions. The immunostaining was dot-like in the cytoplasm and homogeneous in the nuclei in both benign and malignant lesions. Statistically significant relations were observed between nuclear expression of pStat3-ser727 and the pleomorphism score (p = 0.006), mitotic activity (p < 0.0001), and histological grade (p < 0.0001). In contrast, no significant correlations were observed for cytoplasmic pStat3-ser727. These findings add new and interesting information on the potential role of the phosphorylated form of Stat3 in malignant lesions.


Assuntos
Carcinoma/veterinária , Doenças do Gato/metabolismo , Neoplasias Mamárias Animais/metabolismo , Fator de Transcrição STAT3/biossíntese , Animais , Carcinoma/metabolismo , Carcinoma/patologia , Doenças do Gato/patologia , Gatos , Feminino , Imuno-Histoquímica/veterinária , Neoplasias Mamárias Animais/patologia , Fosforilação , Fator de Transcrição STAT3/metabolismo , Serina/metabolismo , Estatísticas não Paramétricas
10.
Vet Res Commun ; 30(6): 599-611, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16838202

RESUMO

The expression of Stat3 (signal transducer and activator of transcription 3) in normal and neoplastic feline mammary gland tissue was assessed by immunohistochemistry in 72 cats. The samples included 3 normal nonlactating mammary tissues, 17 hyperplastic lesions (11 lobular and 6 fibroepithelial) and 52 neoplasms (5 benign and 47 malignant). For immunohistochemistry, tissue sections were incubated with anti-Stat3 monoclonal antibody and visualized with EnVision-DAB polymer. Stat3 positivity was assessed in a semiquantitative manner. Normal mammary tissue showed occasional cytoplasmic and nuclear positivity, although the number of positive cells was lower than in the hyperplastic specimens. In neoplastic tissue, high numbers of neoplastic cells with a moderate to intense cytoplasmic and nuclear positivity were observed. Selected variations in the staining pattern correlated with malignancy. Moreover, a positive association was seen between the histological grade and the Stat3 score (p < 0.0001; correlation coefficient 0.750). A linear regression model showed a positive association between mitotic count and Stat3 expression (p < 0.001). These results further support published data found in humans regarding to the relation between the expression of Stat3 and malignancy.


Assuntos
Doenças do Gato/metabolismo , Regulação Neoplásica da Expressão Gênica , Glândulas Mamárias Animais/metabolismo , Neoplasias Mamárias Animais/metabolismo , Fator de Transcrição STAT3/metabolismo , Animais , Anticorpos Monoclonais , Biomarcadores Tumorais/metabolismo , Estudos de Casos e Controles , Doenças do Gato/patologia , Gatos , Feminino , Imuno-Histoquímica/veterinária , Modelos Lineares , Neoplasias Mamárias Animais/patologia , Índice Mitótico , Estadiamento de Neoplasias/veterinária , Sensibilidade e Especificidade
11.
Oncogene ; 25(16): 2328-38, 2006 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-16314837

RESUMO

We have characterized comprehensive transcript and proteomic profiles of cell lines corresponding to normal breast (MCF10A), noninvasive breast cancer (MCF7) and invasive breast cancer (MDA-MB-231). The transcript profiles were first analysed by a modified protocol for representational difference analysis (RDA) of cDNAs between MCF7 and MDA-MB-231 cells. The majority of genes identified by RDA showed nearly complete concordance with microarray results, and also led to the identification of some differentially expressed genes such as lysyl oxidase, copper transporter ATP7A, EphB6, RUNX2 and a variant of RUNX2. The altered transcripts identified by microarray analysis were involved in cell-cell or cell-matrix interaction, Rho signaling, calcium homeostasis and copper-binding/sensitive activities. A set of nine genes that included GPCR11, cadherin 11, annexin A1, vimentin, lactate dehydrogenase B (upregulated in MDA-MB-231) and GREB1, S100A8, amyloid beta precursor protein, claudin 3 and cadherin 1 (downregulated in MDA-MB-231) were sufficient to distinguish MDA-MB-231 from MCF7 cells. The downregulation of a set of transcripts for proteins involved in cell-cell interaction indicated these transcripts as potential markers for invasiveness that can be detected by methylation-specific PCR. The proteomic profiles indicated altered abundance of fewer proteins as compared to transcript profiles. Antisense knockdown of selected transcripts led to inhibition of cell proliferation that was accompanied by altered proteomic profiles. The proteomic profiles of antisense transfectants suggest the involvement of peptidyl-prolyl isomerase, Raf kinase inhibitor and 80 kDa protein kinase C substrate in mediating the inhibition of cell proliferation.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/química , Neoplasias da Mama/genética , Perfilação da Expressão Gênica , Proteínas de Neoplasias/análise , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Proteômica
13.
J Radiol ; 82(9 Pt 1): 1009-11, 2001 Sep.
Artigo em Francês | MEDLINE | ID: mdl-11591931

RESUMO

The authors report the MR features of a non functioning and hemorragic islet-cell tumor of the pancreas. This tumor was composed of a central cystic component with a fluid-fluid level seen on T1- and T2-weighted images and a peripheral hypervascular soft tissue component which showed hyperintensity on T2-weighted images with fat saturation.


Assuntos
Carcinoma de Células das Ilhotas Pancreáticas/patologia , Imageamento por Ressonância Magnética , Neoplasias Pancreáticas/patologia , Adulto , Carcinoma de Células das Ilhotas Pancreáticas/complicações , Feminino , Hemorragia/etiologia , Hemorragia/patologia , Humanos , Pancreatopatias/etiologia , Pancreatopatias/patologia , Neoplasias Pancreáticas/complicações
14.
J Biol Chem ; 275(22): 16963-8, 2000 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-10747994

RESUMO

Elongation factor 3 (EF-3) is an ATPase essential for polypeptide chain synthesis in a variety of yeasts and fungi. We used limited proteolysis to study the organization of the subdomains of EF-3. Trypsinolysis of EF-3 at 30 degrees C resulted in the formation of three fragments with estimated molecular masses of 90, 70, and 50 kDa. Yeast ribosomes protected EF-3 and the large fragments from further degradation. ATP exposed a new tryptic cleavage site and stabilized the 70- and 50-kDa fragments. The conformation of EF-3 as measured by fluorescence spectroscopy did not change upon ATP binding. Poly(G) stimulated proteolysis and quenched the intrinsic fluorescence of EF-3. Using gel mobility shift, we demonstrated a direct interaction between EF-3 and tRNA. Neither tRNA nor rRNA altered the tryptic cleavage pattern. The proteolytic products were sequenced by mass spectrometric analysis. EF-3 is blocked NH(2)-terminally by an acetylated serine. The 90-, 70-, and 50-kDa fragments are also blocked NH(2)-terminally, confirming their origin. The 50-kDa fragment (Ser(2)-Lys(443)) is the most stable domain in EF-3 with no known function. The 70-kDa fragment (Ser(2)-Lys(668)) containing the first nucleotide-binding sequence motif forms the core ATP binding subdomain within the 90-kDa domain. The primary ribosome binding site is located near the loosely structured carboxyl-terminal end.


Assuntos
Proteínas Fúngicas , Fatores de Alongamento de Peptídeos/metabolismo , Saccharomyces cerevisiae/metabolismo , Sequência de Aminoácidos , Hidrólise , Cinética , Dados de Sequência Molecular , Fatores de Alongamento de Peptídeos/química , Mapeamento de Peptídeos , Proteínas de Saccharomyces cerevisiae , Tripsina/metabolismo
15.
J Neurol Sci ; 164(1): 64-71, 1999 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-10385050

RESUMO

Neuropathy has been frequently reported in patients with IgG monoclonal gammopathy of undetermined significance (MGUS) but it is still unclear whether this association has clinical or pathogenetic relevance. In order to clarify the possible role of IgG MGUS in the neuropathy we correlated the clinical and electrophysiological features of the neuropathy with the duration and anti-neural activity of the M-protein in 17 patients with neuropathy and IgG MGUS. Ten patients (59%) had a chronic demyelinating neuropathy clinically indistinguishable from chronic inflammatory demyelinating polyneuropathy (CIDP) while 7 (41%) had a predominantly sensory axonal or mixed neuropathy. In 80% of patients in the CIDP-like and 28% in the sensory group the IgG M-protein became manifest several months to years after onset of the neuropathy. Antibodies to one or more neural antigens (including tubulin, a 35KD P0-like nerve myelin glycoprotein, GD1a, GM1 and chondrotin sulfate C) were found in 40% of patients with CIDP-like and 43% with sensory neuropathy but also in 37% patients with IgG MGUS without neuropathy. Neuropathy associated with IgG MGUS is probably less heterogeneous than previously considered suggesting that this association may not be merely casual. The evidence for primary pathogenetic role of IgG M-proteins in the neuropathy remains however elusive.


Assuntos
Doenças Desmielinizantes/sangue , Neuropatia Hereditária Motora e Sensorial/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Paraproteinemias/sangue , Adulto , Idoso , Doenças Desmielinizantes/complicações , Doenças Desmielinizantes/terapia , Feminino , Neuropatia Hereditária Motora e Sensorial/complicações , Neuropatia Hereditária Motora e Sensorial/terapia , Humanos , Imunoterapia , Masculino , Pessoa de Meia-Idade , Paraproteinemias/complicações , Paraproteinemias/terapia , Nervo Sural
16.
Tumour Biol ; 20 Suppl 1: 1-12, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10628402

RESUMO

Twelve research groups participated in the ISOBM TD-3 Workshop in which the reactivity and specificity of 83 antibodies against prostate-specific antigen (PSA) were investigated. Using a variety of techniques including cross-inhibition assays, Western blotting, BIAcore, immunoradiometric assays and immunohistochemistry, the antibodies were categorized into six major groups which formed the basis for mapping onto two- and three-dimensional (2-D and 3-D) models of PSA. The overall findings of the TD-3 Workshop are summarized in this report. In agreement with all participating groups, three main antigenic domains were identified: free PSA-specific epitopes located in or close to amino acids 86-91; discontinuous epitopes specific for PSA without human kallikrein (hK2) cross-reactivity located at or close to amino acids 158-163; and continuous or linear epitopes shared between PSA and hK2 located close to amino acids 3-11. In addition, several minor and partly overlapping domains were also identified. Clearly, the characterization of antibodies from this workshop and the location of their epitopes on the 3-D model of PSA illustrate the importance of selecting appropriate antibody pairs for use in immunoassays. It is hoped that these findings and the epitope nomenclature described in this TD-3 Workshop are used as a standard for future evaluation of anti-PSA antibodies.


Assuntos
Mapeamento de Epitopos , Antígeno Prostático Específico/imunologia , Anticorpos Monoclonais/química , Reações Cruzadas , Epitopos/imunologia , Humanos , Imuno-Histoquímica , Modelos Moleculares , Estrutura Terciária de Proteína , Terminologia como Assunto
17.
Tumour Biol ; 20 Suppl 1: 86-93, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10628414

RESUMO

Epitope mapping analysis was performed on 53 antibodies submitted to the ISOBM TD-3 PSA Workshop. Western blotting and N-terminal amino acid sequencing, using both native and recombinant human prostate-specific antigen (rPSA), identified four different epitope groups for native PSA. Under reducing conditions native PSA was not recognized by 18/53 antibodies suggesting they reacted with conformation-dependent epitopes. Nine other antibodies reacted with a rPSA polypeptide doublet of 34-35 kD corresponding to different rPSA glycoforms. From sequence mapping studies 22/53 antibodies bound epitopes within amino acid residues 25-85, 3/53 antibodies bound to epitopes within residues 86-220, while 10/53 antibodies bound epitopes within residues 221-261. These results indicate that there are multiple immunogenic epitopes localized on the PSA molecule.


Assuntos
Anticorpos Monoclonais/imunologia , Antígeno Prostático Específico/imunologia , Reações Antígeno-Anticorpo , Baculoviridae/metabolismo , Western Blotting , Clonagem Molecular , DNA Complementar/imunologia , Eletroforese em Gel de Poliacrilamida , Mapeamento de Epitopos , Humanos , Masculino , Próstata/imunologia , Antígeno Prostático Específico/genética , Conformação Proteica , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Sêmen/imunologia , Análise de Sequência de Proteína
18.
Pediatr Allergy Immunol ; 9(3): 130-2, 1998 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9814726

RESUMO

Plasma levels of cAMP and serum concentrations of IgE have been determined in children with acute atopic dermatitis (AD) and in a healthy control group, to illuminate the pathophysiological mechanisms that cause AD. There were significantly lower plasma levels of cAMP (P < 0.001) and significantly higher levels of serum IgE (P < 0.004) in children with AD, in comparison with a healthy control group. It is possible that defective control of c-AMP levels could contribute to the immunopathogenesis of AD and monitoring levels may be of value in the clinical evaluation of the disease.


Assuntos
AMP Cíclico/sangue , Dermatite Atópica/sangue , Imunoglobulina E/sangue , Pré-Escolar , Dermatite Atópica/imunologia , Feminino , Humanos , Lactente , Masculino , Radioimunoensaio
19.
Blood Cells Mol Dis ; 24(1): 31-40, 1998 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9516379

RESUMO

A major pathway for K+ efflux in human reticulocytes and young RBCs is K:Cl cotransport (K:Cl-CT). The activity of K:Cl-CT is increased in pathologic RBCs containing hemoglobins S and C and may contribute to the abnormal dehydration state of these cells. Human K:Cl-CT (gene product KCC1) has been recently sequenced from human (hKCC1), rabbit and rat tissue by Gillen et al. (J Biol Chem 271:16237, 1996). We report here the sequence of KCC1 from human and mouse erythroleukemic cells (K562 and MEL cells, respectively). The cDNA for human erythroid-KCC1 is 100% identical to hKCC1 and the cDNA for mouse erythroid-KCC1 shares 89% identity with hKCC1, which translates to 96% identity at the amino acid level. Mammalian KCC1 is strongly conserved with >95% identity between human, rabbit, rat, and mouse KCC1 proteins. We did not detect any full-length mRNA transcripts of human erythroid-KCC1 in circulating reticulocytes. We detected two mRNA isoforms of human erythroid-KCC1 that resulted in C-terminal truncated proteins (73 amino acid and 17 amino acids, respectively). Human and mouse erythroidKCC1 differed at several consensus sites including a predicted PKC phosphorylation site at 108threonine and a predicted CK2 phosphorylation site at 51serine, within the predicted cytoplasmic N-terminal, that are present in human but not mouse erythroid-KCC1. Expression of MEL-KCC1 mRNA increases substantially upon DMSO-induced differentiation opening the possibility that erythroid-KCC1 plays a role in early erythroid maturation events. The molecular identification of erythroid-KCC1 is an important step towards understanding the physiologic role mediated by this protein in young and pathologic RBCs and during erythropoiesis, as well as providing a new tool for the elucidation of pathways and signals involved in RBC volume regulation.


Assuntos
Proteínas de Transporte/sangue , Cloretos/sangue , Leucemia Eritroblástica Aguda/metabolismo , Potássio/sangue , Reticulócitos/metabolismo , Simportadores , Sequência de Aminoácidos , Animais , Clonagem Molecular , Envelhecimento Eritrocítico/fisiologia , Humanos , Camundongos , Dados de Sequência Molecular , Conformação Proteica , Homologia de Sequência de Aminoácidos , Células Tumorais Cultivadas , Regulação para Cima , Cotransportadores de K e Cl-
20.
G Chir ; 19(4): 175-83, 1998 Apr.
Artigo em Italiano | MEDLINE | ID: mdl-9628068

RESUMO

Still today the digestive anastomoses are a subject very discuss and controversial in relation to the better technique. In fact the introduction of mechanical suture has placed the problem between this instrumentation and the classic technique. The Authors, comparing these two techniques, observe the peculiar aspects of each one and relate on the progresses, in last years, whether of the mechanical suture, with the improvement of the handy and the resistance of the anastomosis, or the threads of suture, ever more inert and resistant. Subsequently, the Authors relate your experience showing the form of realization of the anastomoses in the esophagogastric surgery, small intestine, colon-rectum, hepato-biliary and pancreatic surgery. In particularly, about the hand-sewn anastomosis, the Authors relate personal technique of reconstruction with extramucosal continuous suture, one-layer, with synthetic slow absorbable one-filament (PDS). In conclusion, the Authors declare that the introduction of the mechanical suture has certainly influenced the development of the new therapeutic solutions and has allowed intestinal anastomosis in sites of difficult access (abdominal esophagus, low rectum), but they think that the surgeon must to learn to know when is useless or neoplastic mechanical suture and he can realize manually the same anastomosis with quickness and safety.


Assuntos
Anastomose Cirúrgica , Procedimentos Cirúrgicos do Sistema Digestório , Grampeadores Cirúrgicos , Técnicas de Sutura , Procedimentos Cirúrgicos do Sistema Biliar , Colo/cirurgia , Esôfago/cirurgia , Humanos , Intestino Delgado/cirurgia , Fígado/cirurgia , Pâncreas/cirurgia , Reto/cirurgia , Estômago/cirurgia
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