RESUMO
BACKGROUND: Transient global amnesia (TGA) is a rare, benign condition characterised by a sudden deficit of anterograde and retrograde memory that usually lasts for a few hours and is not accompanied by other focal neurological symptoms or signs. Its aetiology is still unclear. Various events or activities may trigger TGA. Evidence of seasonal variations in the appearance of TGA is inconsistent. METHODS: We retrospectively analysed the medical history of 114 adult patients with diagnosed TGA, hospitalised at two neurology departments in Wroclaw from 2008 to 2014. We reviewed risk factors, trigger points, and occurrence in each month of the year in our patient population. RESULTS: Over this seven-year period, 114 patients were diagnosed with TGA. The annual occurrence ranged from 13 to 22 hospitalisations. The mean age of the patients was 64 years. There were 36 TGA events in men and 78 in women. TGA occurred most frequently in spring (36%) and summer (30%), with the incidence peaking during March. CONCLUSIONS: Our findings suggest that there is a relationship between the season of the year and the probability of TGA.
Assuntos
Amnésia Global Transitória , Idoso , Feminino , Humanos , Incidência , Masculino , Estudos Retrospectivos , Fatores de Risco , Estações do AnoRESUMO
Cerebellar stroke is a rare condition with very nonspecific clinical features. The symptoms in the acute phase could imitate acute peripheral vestibular disorders or a brainstem lesion. The aim of this study was to assess the usefulness of the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification in cerebellar stroke and the impact of clinical features on the prognosis. We retrospectively analyzed 107 patients with diagnosed ischemic cerebellar infarction. We studied the clinical features and compared them based on the location of the ischemic lesion and its distribution in the posterior interior cerebellar artery (PICA), superior cerebellar artery (SCA), and anterior inferior cerebellar artery (AICA) territories. According to the TOAST classification, stroke was more prevalent in atrial fibrillation (26/107) and when the lesion was in the PICA territory (39/107). Pyramidal signs occurred in 29/107 of patients and were more prevalent when the lesion was distributed in more than two vascular regions (p = 0.00640). Mortality was higher among patients with ischemic lesion caused by cardiac sources (p = 0.00094) and with pyramidal signs (p = 0.00640). The TOAST classification is less useful in assessing supratentorial ischemic infarcts. Cardioembolic etiology, location of the ischemic lesion, and pyramidal signs support a negative prognosis.
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Artérias/patologia , Doenças Cerebelares/diagnóstico , Isquemia/diagnóstico , Acidente Vascular Cerebral/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Cerebelares/patologia , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Humanos , Isquemia/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/patologiaRESUMO
UNLABELLED: Chemotherapy-induced sensory neuropathies differ in clinical picture. There is predominance of paresthesiae in some of them while in others pain or deep sensation failure can dominate. THE AIM OF THE STUDY: To perform the clinical and electrophysiological assessment of peripheral sensory nerves in patients with multiple myeloma (m.m.) treated with thalidomide. Special attention was directed to function of subtypes of sensory fibres which convey different modalities of sensation. MATERIAL AND METHODS: Twenty seven m.m. patients and 30 controls were examined. Neurological examination together with allocation to different groups acc. to sNCI-CTC scale were performed. Standard sensory conduction velocity was measured in ulnar and sural nerves. Quantitative Sensory Testing (QST) was used to determine thermal detection thresholds. RESULTS: All patients informed about subjective positive sensory symptoms and sensory deficit of symmetrical, distal pattern was found in them. Electroneurography revealed axonal and demyelinating abnormalities with dominance of axonal injury. Warm and heat-pain detection thresholds were elevated, while threshold for skin cooling was decreased both in palm and foot in m.m. patients in comparison with controls. There were no differences in the thresholds for cold-pain detection between examined groups. CONCLUSIONS: Thalidomide-induced sensory neuropathy can appear shortly after the introduction of treatment. Patients with longer duration of treatment or with higher cumulative dose present higher degree of neuropathy acc. to the sCNI-CTC scale. Sensory deficit in thalidomide' neuropathy is associated with dysfunction in A delta and C caliber primary afferent fibres.
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Mieloma Múltiplo/tratamento farmacológico , Transtornos de Sensação/induzido quimicamente , Transtornos de Sensação/diagnóstico , Talidomida/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Eletrodiagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Condução Nervosa , Exame Neurológico , Parestesia/induzido quimicamente , Parestesia/diagnósticoRESUMO
BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder with a characteristic clinical picture. Apart from classical movement disorders, a significant role is also played by non-motor symptoms, in particular cognitive impairments, which have a significant impact on the quality of life of the patients. Tau protein and amyloid beta are well-known non-specific biomarkers in Alzheimer's disease (AD). OBJECTIVES: The study assessed the practical value of determining tau protein and amyloid beta (Aß42) in the blood serum of patients with PD and their relationship with cognitive impairments, radiographic image and the used dose of L-DOPA. MATERIAL AND METHODS: The neuropsychological assessment was carried for 64 patients with PD. The levels of amyloid beta 1-42 (Aß42) and tau proteins in serum were also measured. RESULTS: The Aß42 level in the serum was statistically higher in patients with longer duration of the disease (p < 0.05) and those who were taking a higher dose of L-DOPA (p < 0.05). The average level of tau protein in the serum was slightly lower in the study groups than in the control group and showed no statistical significance. No correlation was found between the levels of tau protein and Aß42 and the results of neuropsychological tests. Tau protein correlated with hippocampal atrophy (p < 0.05). CONCLUSIONS: Serum levels of Aß42 and tau protein in PD may be a useful marker for the assessment of cognitive impairments. The role of L-DOPA in the process of dementia in PD remains unclear.
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Doença de Alzheimer , Peptídeos beta-Amiloides , Disfunção Cognitiva , Doença de Parkinson , Fragmentos de Peptídeos , Proteínas tau , Adulto , Idoso , Peptídeos beta-Amiloides/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Disfunção Cognitiva/sangue , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Fragmentos de Peptídeos/sangue , Qualidade de Vida , Proteínas tau/sangueRESUMO
Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is an important molecule in the down-regulation of T-cell activation. A study was undertaken to evaluate the association of the CTLA-4 gene polymorphisms -319C/T, +49A/G, (AT)(n), CT60A/G and Jo31G/T with the levels of membrane CTLA-4 (mCTLA-4) and cytoplasmic CTLA-4 (cCTLA-4) in CD4(+) T lymphocytes from patients with multiple sclerosis (MS) and with susceptibility to MS, and the course of the disease. It was found that the Jo31GG and CT60GG genotypes were associated with decreased mean fluorescence intensity (MFI) of total CTLA-4 (mCTLA-4 + cCTLA-4) molecules in CD4(+) T cells from both relapsing-remitting (RR) and secondary progressive (SP) MS patients compared with others. Consequently, possessing the Jo31G allele and/or the CT60G allele were associated with susceptibility to MS. The percentages of cells expressing mCTLA-4 and cCTLA-4 in RR patients were higher in carriers of the alleles non-predisposing to MS (namely CT60A and Jo31T), but the percentages of corresponding cells were unexpectedly significantly lower in SP patients than in RR patients. Increased risk of paresthesia and pyramidal signs as a first manifestation of disease, and earlier transition to the SP form in those patients, was also noted. It is hypothesized that the decreasing frequencies of cells expressing immunosuppressive mCTLA-4 and cCTLA-4 in carriers of alleles non-predisposing to MS (i.e. CT60A and Jo31T) may lead to inadequate down-regulation of ongoing T-cell responses in these patients and, as a consequence, earlier progression of disease from the RR form to the SP form.
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Antígenos CD/biossíntese , Antígenos CD/genética , Linfócitos T CD4-Positivos/imunologia , Predisposição Genética para Doença , Esclerose Múltipla/genética , Esclerose Múltipla/imunologia , Adulto , Alelos , Antígeno CTLA-4 , Feminino , Frequência do Gene/genética , Haplótipos , Humanos , Estimativa de Kaplan-Meier , Desequilíbrio de Ligação/genética , Ativação Linfocitária/genética , Ativação Linfocitária/imunologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
INTRODUCTION: The modification of p53 protein by phosphorylation plays an important role in its stabilization and the regulation of its biological properties. The study investigated the expression of p53 protein phosphorylated at serine 20 (Ser20) and Ser392 and the association between clinicopathological parameters of ovarian neoplasms with respect to p53 protein overexpression. METHODS: p53 protein expression was evaluated on tissues from malignant and benign ovarian tumors. Protein expression was measured in a subset of the specimens using immunohistochemistry. RESULTS: The correlation between p53 protein overexpression and p53-Ser392 phosphorylation was found in ovarian carcinomas (P = 0.001, r = +0.27). In the total group of ovarian carcinomas, significant differences were observed in p53 protein overexpression between well (G1) and poor (G3) tumor grades (P = 0.005) and between serous and endometrioid types of tumor (P = 0.04), whereas p53-Ser20 phosphorylation was associated with advanced International Federation of Gynecology and Obstetrics stage (P = 0.004) and high tumor grade (P = 0.02). In p53-positive ovarian carcinomas, p53-Ser392 phosphorylation was associated with advanced tumor stage (P = 0.02) and high tumor grade (P = 0.049). p53-Ser20 phosphorylation was associated with low tumor grade of p53-positive ovarian carcinomas (P = 0.02) and with high tumor grade of p53-negative ovarian carcinomas (P = 0.02). CONCLUSIONS: These results revealed that p53 phosphorylation at Ser20 and Ser392 is an early event in ovarian tumor development. The authors suggest that the expression of p53 protein phosphorylated at Ser20 and Ser392 in ovarian carcinomas determines their individual clinical features depending on p53 protein status and may be useful biological biomarkers characterizing their behavior.
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Adenocarcinoma Mucinoso/metabolismo , Cistadenocarcinoma Seroso/metabolismo , Neoplasias do Endométrio/metabolismo , Neoplasias/metabolismo , Neoplasias Ovarianas/metabolismo , Serina/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Adenocarcinoma Mucinoso/secundário , Adulto , Idoso , Cistadenocarcinoma Seroso/secundário , Neoplasias do Endométrio/secundário , Feminino , Humanos , Técnicas Imunoenzimáticas , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias/patologia , Neoplasias Ovarianas/patologia , Fosforilação , Prognóstico , Serina/química , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: Interleukin 6 (IL-6) is one of the mediators of inflammation in the neurodegenerative process in Alzheimer's disease (AD). The aim of the study was to identify the risk of AD incidence in carriers of the polymorphism of genotype IL-6-174G/C. MATERIAL AND METHODS: The study covered 51 patients (34 women and 17 men, average age: 73.0+/-6.9 years) who met the NINCDS-ADRDA criteria of probable diagnosis of Alzheimer's disease and 36 patients (29 women and 7 men, average age: 73.5+/-8.2 years) without dementia features who constituted the control group. DNA was extracted from the blood by means of a QIAamp DNA Blood Mini Kit. IL-6 polymorphism was identified by the PCR method. RESULTS: Genotype IL-6 C/C occurred in 22.2% of patients of the control group and in 17.6% of AD patients. The genotype IL-6-174G/C occurred in 44.5% of patients of the control group and in 60.8% of patients of the AD group. The differences in genotype frequencies were not statistically significant in the examined groups (p=0.30). Differences in the frequencies of the C and G alleles in both groups (p=0.64) were not statistically significant. Analysis of the frequencies of genotypes IL-6 C/C, 174-G/C, and G/G depending on sex showed a little more frequent occurrence of IL-6 G/G and IL-6-174G/C in women suffering from AD (p=0.045). CONCLUSIONS: This preliminary report shows no connection between polymorphism of IL-6 and the incidence of AD. The study may confirm the regional differentiation of IL-6 polymorphism in AD.
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Doença de Alzheimer/genética , Interleucina-6/genética , Polimorfismo Genético/genética , Regiões Promotoras Genéticas/genética , Idoso , Estudos de Casos e Controles , DNA/sangue , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodosRESUMO
The potential role of microbiological factors such as Chlamydia pneumoniae (ChP) in the pathogenesis of neurodegenerative disorders, including Alzheimer's disease (AD) and vascular dementia (VD), has been suggested, but the correctness of this hypothesis still needs to be tested. In this study the appearance of ChP in the cerebrospinal fluid (CSF) of 57 AD and 21 VD patients and in 47 controls (CG) as well as the influence of ChP on the levels of tau protein and Abeta42 were investigated. The frequency of ChP occurrence in the AD patient group (43.9%) was significantly higher (p < 0.001) than in the control group (10.6%). In the case of VD patients, 9.5% of this group was positive for ChP. The presence of ChP DNA in the CSF of patients with AD significantly increases the occurrence of this disease (odds ratio = 7.21). Cerebrospinal fluid Abeta42 levels were significantly lower in patients with AD than in the CG (p < 0.001). Cerebrospinal tau protein was significantly higher in AD vs. CG (p = 0.007). However, no relationships between the presence of the bacterium in CSF and the level of either tau or Abeta42 protein were observed. In conclusion, we may suspect that testing for the presence of ChP in CSF, along with the tau and Abeta42 markers, may be used in the clinic diagnosis of AD.
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Doença de Alzheimer/líquido cefalorraquidiano , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Chlamydophila pneumoniae/isolamento & purificação , Demência Vascular/líquido cefalorraquidiano , Fragmentos de Peptídeos/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Feminino , Humanos , Masculino , Razão de ChancesRESUMO
AIM: The aim of this study was to investigate heat shock protein 90 (HSP90) and topoisomerase I (Topo I) expression and the association between both proteins and clinicopathological parameters of colorectal cancer (CRC), in order to describe their role in tumor biology regarding to Kirsten Ras (KRAS) - positive/negative cases. MATERIALS AND METHODS: Expression of HSP90 and Topo I, and KRAS gene mutations were estimated in primary CRCs. RESULTS: HSP90/Topo I immunophenotype correlated with gender, Duke staging, tumor grade and lymph node metastasis (p<0.01). Positive correlation was found between KRAS mutation and HSP90 expression (p=0.02). HSP90, Topo I expression, and co-expression of HSP90/Topo I correlated with unfavorable parameters of CRCs in respect to KRAS gene status (p<0.001). CONCLUSION: Our results revealed that cooperation between HSP90 and Topo I expression exists in CRCs, independently of KRAS gene status, suggesting that co-expression of both proteins might be considered as a double target on individual tumor cells.
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Adenocarcinoma/secundário , Neoplasias Colorretais/patologia , DNA Topoisomerases Tipo I/metabolismo , Proteínas de Choque Térmico HSP90/metabolismo , Mutação , Proteínas Proto-Oncogênicas p21(ras)/genética , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Feminino , Seguimentos , Humanos , Imunofenotipagem , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , PrognósticoRESUMO
INTRODUCTION: The differences in drug efficacy and adverse reactions may be caused by genetic variations in drug metabolism between individuals. OBJECTIVES: The aim of the study was to evaluate the effect of gene polymorphisms on the efficacy of therapy and side effects in patients with rheumatoid arthrit s (RA) treated with methotrexate (MTX). PATIENTS AND METHODS: A total of 273 Caucasian patients with RA were treated with MTX for at least 6 months or stopped MTX because of adverse effects. Seven polymorphisms (RFC-1 c.80G>A, GGH c.-401C>T, MTHFR c.1298A>C and c.677C>T, TYMS 2R/3R, TYMS 6-bp deletion, and TCII c.593T>C) were examined for their effects on MTX efficacy and toxicity. Genomic DNA was obtained from peripheral blood leukocytes. RESULTS: Of all patients, 53% reported some adverse effects during at least 1 visit, which led to MTX withdrawal in 17% of the patients. Adverse effects were more frequent in patients with the MTHFR 677T allele than in those with the 677CC genotype (odds ratio [OR], 1.97; P = 0.01) and in those with the GGH 401CC genotype than in those with the GGH 401CT and TT genotypes (OR, 3.8; P = 0.05). Furthermore, the MTHFR 677T allele was associated with increased activity of aminotransferases (OR, 3.4; P = 0.02). MTX-related hepatotoxicity and alopecia were more common in patients with the RFC-1 80AA genotype (OR, 3.5, P = 0.01; OR, 2.4, P = 0.04; respectively). A more rapid positive response to MTX therapy was demonstrated in MTHFR 677CC homozygotes (OR, 3.4; P = 0.001). There were no other associations between single -nucleotide polymorphisms and the efficacy of MTX treatment. CONCLUSIONS: The MTHFR 677CC and GGH 401TT and CT genotypes were associated with a reduction in the number of MTX-related adverse events. Future allele and genotype analyses may help identify the subsets of RA patients with an increased risk of adverse effects.
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Antirreumáticos/toxicidade , Artrite Reumatoide/genética , Ciclina D1/genética , Metotrexato/toxicidade , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Proteína Carregadora de Folato Reduzido/genética , Timidilato Sintase/genética , Artrite Reumatoide/tratamento farmacológico , Feminino , Frequência do Gene , Humanos , Masculino , Polimorfismo Genético , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: The posterior cingulate region is an area of the earliest pathological changes in amnestic mild cognitive impairment (aMCI). The utility of FDG-PET imaging in dementia is already well established. OBJECTIVES: The aim of the study was to compare FDG-PET with advanced MR measurements: MR spectroscopy (MRS), perfusion weighted imaging (PWI), and diffusion tensor imaging (DTI) within the posterior cingulate region in patients with aMCI. METHODS: Fifty-five patients diagnosed with aMCI (66.5 y) and 20 age-matched controls (69 y) underwent MR examination including MRS, PWI, and DTI followed by FDG-PET scanning. Values of MRS metabolite ratios (NAA/Cr, Cho/Cr, mI/Cr), PWI cerebral blood volume (rCBV), and DTI fractional anisotropy (FA) were compared to the FDG-PET rates of glucose metabolism. RESULTS: Compared to controls, aMCI patients showed significant (p < 0.05) glucose hypometabolism, and lower rCBV and FA values. FDG-PET results correlated significantly with rCBV values. Compared to FDG-PET, PWI showed similar and DTI greater accuracy in distinguishing aMCI from controls. According to FDG-PET findings, two groups of aMCI patients were established: those with lower (PET-positive) and normal (PET-negative) glucose uptake. PET-positive aMCI subjects showed normal MRS findings, lower rCBV and FA values, while PET-negative patients revealed normal MRS and PWI results but significantly lower FA values. CONCLUSIONS: Advanced MR techniques such as PWI and particularly DTI may be regarded as competitive techniques to FDG-PET. DTI was the only method to show alterations in aMCI patients with normal FDG-PET, PWI, and MRS findings. DTI seems to be a very sensitive biomarker of early degeneration in aMCI.
Assuntos
Disfunção Cognitiva/patologia , Diagnóstico por Imagem , Fluordesoxiglucose F18 , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/patologia , Idoso , Amnésia/complicações , Anisotropia , Estudos de Casos e Controles , Disfunção Cognitiva/etiologia , Imagem de Tensor de Difusão , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Imagem de Perfusão , Tomografia por Emissão de Pósitrons , Análise de Regressão , Estudos RetrospectivosRESUMO
Genomic instability has long been recognized as the main feature of neoplasia and a factor modulating individual cancer susceptibility. There are attempts to find effective assays of both individual DNA repair capacity and genetic instability, and their relation to the cancer risk. Genetic predisposition plays an important role in the etiology and development of head and neck squamous cell carcinoma (HNSCC). The aim of our study was to search for a correlation between chromosomal instability and DNA repair capacity in HNSCC patients and healthy controls. The chromosomal instability was measured by the number of bleomycin (BLM)-induced chromosomal aberrations and diepoxybutane (DEB)-induced sister chromatid exchanges. The DNA repair capacity was assessed using the DEB-induced adaptive response (AR). The HNSCC patients in our study showed a significant increase in chromosomal instability after a preterminal exposure of their lymphocytes to either BLM for the last 5 h or DEB for the last 24 h of incubation. However, the AR was higher in HNSCC patients than in the control group, suggesting an increase in the DNA repair capacity in the cancer patients as compared to the control. There is no correlation between the DNA repair capacity estimated on the basis of preterminal exposures to BLM and DEB and the DNA repair capacity estimated on the basis of the adaptive response to DEB. The preterminal exposure and the adaptive response test may activate different DNA repair mechanisms.
Assuntos
Aberrações Cromossômicas/efeitos dos fármacos , Reparo do DNA/fisiologia , Neoplasias de Cabeça e Pescoço/genética , Linfócitos/fisiologia , Troca de Cromátide Irmã/efeitos dos fármacos , Antineoplásicos/farmacologia , Bleomicina/farmacologia , Carcinógenos/farmacologia , Reparo do DNA/efeitos dos fármacos , Compostos de Epóxi/farmacologia , Neoplasias de Cabeça e Pescoço/fisiopatologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: The enhanced activity of matrix endopeptidases (MMPs) involved in the degradation of connective tissue has been noted in tissue samples from the digestive tract in inflammatory bowel disease (IBD), however sera concentrations of MMPs, a potential tool for diagnostic tests in IBD patients, have not been established so far. The goal of the studies was to evaluate the concentrations of MMP-3 and MMP-9, in the sera of children suffering from ulcerative colitis (UC) in relation to disease activity. MATERIAL AND METHODS: The study was comprised of 31 children with UC (aged 3-18 years) and 37 children in the control group (aged 1-18 years). Disease activity was estimated using the Truelove-Witts scale. MMP-3 and -9 concentrations were determined using ELISA tests. RESULTS: Median MMP-3 concentrations were 18.4 ng/mL (95% CI: 12.5-24.3) for moderate and severe, 4.35 ng/mL (95% CI: 2.5-7.8) for the mild form of UC and 1.8 ng/mL (95% CI: 1.2-2.5) for the control group. Median MMP-9 concentrations were 18.0 ng/mL (95% CI: 2.83-36.6) for moderate and severe, 1.55 ng/mL (95% CI: 0.4-3.0) for the mild form of UC and 1.3 ng/mL (95% CI: 0.7-1.96) for the control group. Serum MMP-3 and MMP-9 concentrations in the moderate group were higher than those in the mild and control groups (p < 0.001). MMP-3 concentrations in the mild group also differed from those in the control group (p < 0.001). Among the parameters studied (MMP-3, MMP-9, CRP and ESR), MMP-3 had the highest discriminative value (AUC = 0.9, p < 0.001, sensitivity = 71%, specificity = 92%) in distinguishing patients with UC from healthy individuals. CONCLUSIONS: Elevation of MMP-3 and MMP-9 concentrations along with the disease activity suggests the possibility of their application in the evaluation of the clinical activity of UC.
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Colite Ulcerativa/diagnóstico , Metaloproteinase 3 da Matriz/sangue , Metaloproteinase 9 da Matriz/sangue , Adolescente , Biomarcadores/sangue , Sedimentação Sanguínea , Proteína C-Reativa/análise , Criança , Pré-Escolar , Colite Ulcerativa/enzimologia , HumanosRESUMO
BACKGROUND: Gliomas are a heterogenous group of tumors that show the same histological features but differ in their behavior. Gliomas are characterized by biological aggressiveness and extensive infiltrative growth into surrounding healthy brain tissue. OBJECTIVES: In this study we estimated CD44v6 and E-cadherin expression and correlation between CD44v6 and E-cadherin in relation to glioma malignancy. We also analyzed simultaneous expression of CD44v6 and E-cadherin in the same tumor sample in order to determine the biological tumor behavior. MATERIAL AND METHODS: Expression of CD44v6 and E-cadherin was evaluated on ninety-two formalin-fixed paraffin-embedded glioma tissue blocks using immunohistochemistry (IHC). RESULTS: CD44v6 expression was found in 71.6% of gliomas. There was a statistically significant difference between the frequency of positive cases for CD44v6 expression in low (grade I) vs. high (grade IV) as well as in grade I vs. grade II of glioma malignancy (p = 0.001). E-cadherin membrane staining was observed in 28.8% of gliomas. No significant differences were observed between E-cadherin expression and grade of gliomas (p > 0.05). However, re-expression of E-cadherin was found in grade II gliomas. In this group, E-cadherin expression was revealed in 43.3% of the cases. In order to define the relationship between CD44v6 expression and E-cadherin, we analyzed the simultaneous expression of CD44v6 and E-cadherin in the same glioma sample in the whole group and in respect to the degree of glioma malignancy. A positive correlation between studied biomarkers was observed in the analyzed gliomas (p = 0.004) but a simultaneous expression of CD44v6 and E-cadherin revealed no significant differences in respect to glioma malignancy. CONCLUSIONS: Our results showed that the level of E-cadherin might reflect different biological features of gliomas, whereas CD44v6 is associated with tumor cell malignancy. The simultaneous presence of CD44v6 and E-cadherin in a set of low-grade gliomas indicates that both these molecules might strengthen cell migration and may be a hallmark of glioma invasive growth.
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OBJECTIVE: The pathogenesis of idiopathic growth hormone deficiency (GHD) in children, including possible cerebral metabolic alterations, remains unclear. The aim of the study was to evaluate metabolic changes within the normal appearing brain in children with GHD using MR spectroscopy (MRS) and to correlate MRS measurements with hormonal concentrations and with pituitary gland size. METHODS: Seventy children with GHD (mean age 7.8 yrs) and 11 healthy controls (mean age 8.4 yrs) were enrolled in the study. The MRS examinations were performed on a 1.5T scanner. Voxels were located in the posterior cingulate gyrus (PCG) and the left parietal white matter (PWM). The NAA/Cr, Cho/Cr and mI/Cr ratios were analyzed. The metabolite ratios, pituitary gland size and hormonal concentrations: growth hormone (GH) in two stimulation tests and GH during the night, as well as IGF-1 (insulin-like growth factor) and IGFBP3 (insulin-like growth factor-binding protein) levels were also correlated. RESULTS: There was a significant (p < 0.05) decrease of the NAA/Cr ratios in PCG and PWM in children with GHD compared to the normal subjects. Other metabolite ratios showed no significant differences. We also found significant positive correlations between NAA/Cr ratio in PWM and IGFBP3 level, as well as with GH concentration in a stimulation test with glucagon. CONCLUSIONS: The reduction of NAA/Cr ratios may suggest loss of neuronal activity within normal appearing gray and white matters in children with GHD. MRS could be a sensitive marker of cerebral metabolic disturbances associated with GHD and maybe used as an additional indicator for therapy with recombinant GH.
Assuntos
Encéfalo/metabolismo , Substância Cinzenta/metabolismo , Hormônio do Crescimento/deficiência , Substância Branca/metabolismo , Adolescente , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Encéfalo/patologia , Criança , Pré-Escolar , Creatina/metabolismo , Feminino , Substância Cinzenta/patologia , Humanos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino , Tamanho do Órgão , Hipófise/patologia , Curva ROC , Substância Branca/patologiaRESUMO
BACKGROUND: In in vitro studies it has been revealed that p53 protein expression might regulate topoisomerase I (topo I) and topoisomerase IIalpha (topo IIalpha) levels in tumor cells. So far, the association between the p53 protein and topo I and topo IIalpha expression and its impact on ovarian carcinoma progression has not been analyzed. OBJECTIVES: The aim of the study was to examine the association between topo I and topo IIalpha expression and p53 protein overexpression with respect to the morphological features and progressive growth of ovarian tumors. MATERIAL AND METHODS: The expression of the studied biomarkers was estimated by immunohistochemical staining in tumor sections from 136 malignant and 30 benign ovarian neoplasms. RESULTS: Significant differences for topo I, topo IIalpha and p53 expression between malignant and benign tumors were observed (p < 0.01). The expression of topo IIalpha and p53 protein was associated with advanced stages of ovarian carcinomas (p < 0.01). Differences between topo I-positive cases and low (G1) and high (G3) tumor grade had only borderline significance (p = 0.07). In ovarian carcinomas, positive correlations between topo I and topo IIalpha, topo I and p53 and topo Ilalpha and p53 protein expression were revealed (p = 0.001). No relationship between the studied biomarkers was found in benign ovarian tumors (p > 0.05). p53/topo I and p53/topo IIalpha immunophenotypes were associated with advanced stages of ovarian carcinoma (p = 0.045 and p = 0.009, respectively), p53/topo IIalpha positive ovarian carcinomas were more frequently observed in high than in low tumor grades and the differences were only of borderline significance (p = 0.07). CONCLUSIONS: Current findings suggest that on the one hand, cooperation between topo I, topo IIalpha and p53 protein participates in the progressive growth of ovarian tumors. On the other hand, simultaneous expression of the studied proteins identifies the subgroup of ovarian cancers with aggressive biological features which might be considered in therapy.
Assuntos
Antígenos de Neoplasias/análise , Biomarcadores Tumorais/análise , Carcinoma/enzimologia , DNA Topoisomerases Tipo II/análise , DNA Topoisomerases Tipo I/análise , Proteínas de Ligação a DNA/análise , Neoplasias Ovarianas/enzimologia , Proteína Supressora de Tumor p53/análise , Adulto , Idoso , Carcinoma/imunologia , Carcinoma/patologia , Distribuição de Qui-Quadrado , Feminino , Humanos , Imuno-Histoquímica , Imunofenotipagem , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/patologia , Polônia , Adulto JovemRESUMO
The purpose of this study was to assess metabolic, perfusion, and microstructural changes within the posterior cingulate area in patients with Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) using advanced MR techniques such as: spectroscopy (MRS), perfusion weighted imaging (PWI), and diffusion tensor imaging (DTI). Thirty patients with AD (mean age 71.5 y, MMSE 18), 23 with aMCI (mean age 66 y, MMSE 27.4), and 15 age-matched normal controls (mean age 69 y, MMSE 29.5) underwent conventional MRI followed by MRS, PWI, and DTI on 1.5 Tesla MR unit. Several metabolite ratios (N-acetylaspartate [NAA]/creatine [Cr], choline [Ch]/Cr, myoinositol [mI]/Cr, mI/NAA, mI/Cho) as well as parameters of cerebral blood volume relative to cerebellum and fractional anisotropy were obtained in the posterior cingulate region. The above parameters were correlated with the results of neuropsychological tests. AD patients showed significant abnormalities in all evaluated parameters while subjects with aMCI showed only perfusion and diffusion changes in the posterior cingulate area. Only PWI and DTI measurements revealed significant differences among the three evaluated subject groups. DTI, PWI, and MRS results showed significant correlations with neuropsychological tests. DTI changes correlated with both PWI and MRS abnormalities. Of neuroimaging methods, DTI revealed the highest accuracy in diagnosis of AD and aMCI (0.95, 0.79) followed by PWI (0.87, 0.67) and MRS (0.82, 0.47), respectively. In conclusion, AD is a complex pathology regarding both grey and white matter. DTI seems to be the most useful imaging modality to distinguish between AD, aMCI, and control group, followed by PWI and MRS.
Assuntos
Doença de Alzheimer/diagnóstico , Amnésia/diagnóstico , Imagem de Tensor de Difusão/métodos , Giro do Cíngulo/patologia , Espectroscopia de Ressonância Magnética/métodos , Imagem de Perfusão/métodos , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/metabolismo , Amnésia/metabolismo , Diagnóstico Diferencial , Feminino , Giro do Cíngulo/metabolismo , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Loss of basement membrane (BM) components, such as type IV collagen has been demonstrated in ovarian cancer, but the associations with other molecules like CD44v6, involved in metastatic process of ovarian carcinoma, have not been fully analyzed. This study investigates the expression of type IV collagen, CD44v6 molecule in correlation with p53 and Ki-67 presence in primary and metastatic lesion of ovarian carcinoma to define their role in metastases of ovarian carcinoma. METHODS: The expression of type IV collagen, CD44v6, p53, and Ki-67 was evaluated on frozen tissue sections from primary ovarian tumors (malignant n = 37, benign n = 16), metastatic lesions (n = 29) and ascitic fluid cells (n = 28). Protein expression of all studied biomarkers was evaluated in a subset of specimens using immunohistochemistry (IHC). RESULTS: Type IV collagen expression in the primary ovarian carcinoma was positively correlated with International Federation of Gynecology and Obstetrics (FIGO) stage and tumor grade. Significant difference was observed for type IV collagen immunoreactivity in carcinoma cells in effusions when compared to corresponding primary tumors (P < 0.001) and metastatic lesions (P < 0.001). Likewise down-regulation of type IV collagen expression was seen in primary ovarian carcinomas (P = 0.01), ascitic fluid cells (P < 0.001), and metastases (P = 0.003) when compared to benign ovarian neoplasms. CD44v6 expression was detected in a comparable percentage of primary carcinomas (51%) and metastatic lesions (52%). In cells isolated from ascitic fluid, CD44v6 immunopositivity was observed in 43% of cases. A comparative analysis of primary and metastatic tumors and carcinoma cells in effusion did not reveal differences in expression of CD44v6. Positivity of CD44v6 was found in 2/16 (12%) of benign ovarian neoplasms. There were no significant differences between CD44v6 expression in benign neoplasms compared to primary malignant tumors and metastases (P > 0.05). CD44v6 expression in primary ovarian carcinomas was associated with higher tumor grade (P = 0.01) and histological type of tumors (P = 0.01). An inverse relationship of type IV collagen expression with p53 and CD44v6 positivity in benign and malignant ovarian tumors was found (P > 0.01). Type IV collagen expression was inversely correlated with p53 status (P = 0.03) in metastatic lesions. A slight trend toward an inverse correlation between Ki-67 and type IV collagen expression was observed in both benign and malignant ovarian tumors and metastases. CONCLUSIONS: Our data suggest that observed inverse correlation of type IV collagen expression with p53, CD44v6, and slight with Ki-67 positivity in primary benign and malignant tumors indicates that these molecules may cooperate in the invasion and progression of ovarian carcinomas.