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1.
Int J Biol Macromol ; 265(Pt 1): 130420, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38460641

RESUMO

Proteolytic activity constitutes a fundamental process essential for the survival of the malaria parasite and is thus highly regulated. Falstatin, a protease inhibitor of Plasmodium falciparum, tightly regulates the activity of cysteine hemoglobinases, falcipain-2 and 3 (FP2, FP3), by inhibiting FP2 through a single surface exposed loop. However, the multimeric nature of falstatin and its interaction with FP2 remained unexplored. Here we report that the N-terminal falstatin region is highly disordered, and needs chaperone activity (heat-shock protein 70, HSP70) for its folding. Protein-protein interaction assays showed a significant interaction between falstatin and HSP70. Further, characterization of the falstatin multimer through a series of biophysical techniques identified the formation of a falstatin decamer, which was extremely thermostable. Computational analysis of the falstatin decamer showed the presence of five falstatin dimers, with each dimer aligned in a head-to-tail orientation. Further, the falstatin C-terminal region was revealed to be primarily involved in the oligomerization process. Stoichiometric analysis of the FP2-falstatin multimer showed the formation of a heterooligomeric complex in a 1:1 ratio, with the participation of ten subunits of each protein. Taken together, our results report a novel protease-inhibitor complex and strengthens our understanding of the regulatory mechanisms of major plasmodium hemoglobinases.


Assuntos
Cisteína Endopeptidases , Plasmodium falciparum , Dobramento de Proteína
2.
J Nepal Health Res Counc ; 20(3): 755-760, 2023 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-36974870

RESUMO

BACKGROUND: Cervical cancer is a most common preventable public health problem. Despite availability of various screening services at Biratnagar, many barriers restrict its utilization. So, we aimed to assess the knowledge, practice and barriers of cervical cancer screening among 30-60 years married women in Biratnagar, Morang, Nepal. METHODS: We conducted a community based cross sectional study in Biratnagar Morang from December 2020 to December 2021. Consecutive sampling technique was used to collect data from 280 married women of 30-60 years. Ethical approval was obtained from Nepal Health Research Council and informed consent was taken from study participants. Data was collected by face to face interview using a semi structured questionnaire. RESULTS: All participants had heard of cervical cancer. Most (93.9%) responded to multiple sexual partners as a risk factor and 97.9% responded to excessive vaginal bleeding as a symptom. Most (97.1%) responded that cervical cancer is preventable and 44.1% were aware of pap smear test. Eighty-four (30%) participants had ever been screened for cervical cancer. Unavailability of health insurance (85.2%), high cost of treatment (83.1%), lack of nearby service availability (70.9%), embarrassment (44.8%), presence of male doctors (43.8%), problems in time management (28.01%), no advice from health care providers (22.9%), unaware of screening (15.8%) and beliefs on traditional healers (7.1%) were barriers. CONCLUSIONS: In comparison to knowledge, practice of cervical cancer screening is low suggesting existence of know-do gap. Various barriers that prevent cervical cancer screening were evident.


Assuntos
Neoplasias do Colo do Útero , Esfregaço Vaginal , Feminino , Masculino , Humanos , Neoplasias do Colo do Útero/diagnóstico , Detecção Precoce de Câncer , Estudos Transversais , Conhecimentos, Atitudes e Prática em Saúde , Nepal
3.
Epilepsia ; 63(4): 777-788, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35224721

RESUMO

OBJECTIVE: We aimed to assess the reliability and validity of single-item global ratings (GR) of satisfaction with epilepsy surgery. METHODS: We recruited 240 patients from four centers in Canada and Sweden who underwent epilepsy surgery ≥1 year earlier. Participants completed a validated questionnaire on satisfaction with epilepsy surgery (the ESSQ-19), plus a single-item GR of satisfaction with epilepsy surgery twice, 4-6 weeks apart. They also completed validated questionnaires on quality of life, depression, health state utilities, epilepsy severity and disability, medical treatment satisfaction and social desirability. Test-retest reliability of the GR was assessed with the intra-class correlation coefficient (ICC). Construct and criterion validity were examined with polyserial correlations between the GR measure of satisfaction and validated questionnaires and with the ESSQ-19 summary score. Non-parametric rank tests evaluated levels of satisfaction, and ROC analysis assessed the ability of GRs to distinguish among clinically different patient groups. RESULTS: Median age and time since surgery were 42 years (IQR 32-54) and 5 years (IQR 2-8), respectively. The GR demonstrated good to excellent test-retest reliability (ICC = 0.76; 95% CI 0.67-0.84) and criterion validity (0.85; 95% CI 0.81-0.89), and moderate correlations in the expected direction with instruments assessing quality of life (0.59; 95% CI 0.51-0.63), health utilities (0.55; 95% CI 0.45-0.65), disability (-0.51; 95% CI -0.41, -0.61), depression (-0.48; 95% CI -0.38, -0.58), and epilepsy severity (-0.48; 95% CI -0.38, -0.58). As expected, correlations were lower for social desirability (0.40; 95% CI 0.28-0.52) and medical treatment satisfaction (0.33; 95% CI 0.21-0.45). The GR distinguished participants who were seizure-free (AUC 0.75; 95% CI 0.67-0.82), depressed (AUC 0.75; 95% CI 0.67-0.83), and self-rated as having more severe epilepsy (AUC 0.78; 95% CI 0.71-0.85) and being more disabled (AUC 0.82; 95% CI 0.74-0.90). SIGNIFICANCE: The GR of epilepsy surgery satisfaction showed good measurement properties, distinguished among clinically different patient groups, and appears well-suited for use in clinical practice and research.


Assuntos
Epilepsia , Satisfação Pessoal , Epilepsia/cirurgia , Humanos , Psicometria , Qualidade de Vida , Reprodutibilidade dos Testes , Inquéritos e Questionários
4.
Epilepsia ; 62(9): 2103-2112, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34245019

RESUMO

OBJECTIVE: The 19-item Epilepsy Surgery Satisfaction Questionnaire (ESSQ-19) is a validated and reliable post hoc means of assessing patient satisfaction with epilepsy surgery. Prediction models building on these data can be used to counsel patients. METHODS: The ESSQ-19 was derived and validated on 229 patients recruited from Canada and Sweden. We isolated 201 (88%) patients with complete clinical data for this analysis. These patients were adults (≥18 years old) who underwent epilepsy surgery 1 year or more prior to answering the questionnaire. We extracted each patient's ESSQ-19 score (scale is 0-100; 100 represents complete satisfaction) and relevant clinical variables that were standardized prior to the analysis. We used machine learning (linear kernel support vector regression [SVR]) to predict satisfaction and assessed performance using the R2 calculated following threefold cross-validation. Model parameters were ranked to infer the importance of each clinical variable to overall satisfaction with epilepsy surgery. RESULTS: Median age was 41 years (interquartile range [IQR] = 32-53), and 116 (57%) were female. Median ESSQ-19 global score was 68 (IQR = 59-75), and median time from surgery was 5.4 years (IQR = 2.0-8.9). Linear kernel SVR performed well following threefold cross-validation, with an R2 of .44 (95% confidence interval = .36-.52). Increasing satisfaction was associated with postoperative self-perceived quality of life, seizure freedom, and reductions in antiseizure medications. Self-perceived epilepsy disability, age, and increasing frequency of seizures that impair awareness were associated with reduced satisfaction. SIGNIFICANCE: Machine learning applied postoperatively to the ESSQ-19 can be used to predict surgical satisfaction. This algorithm, once externally validated, can be used in clinical settings by fixing immutable clinical characteristics and adjusting hypothesized postoperative variables, to counsel patients at an individual level on how satisfied they will be with differing surgical outcomes.


Assuntos
Epilepsia , Satisfação Pessoal , Adolescente , Adulto , Epilepsia/cirurgia , Feminino , Humanos , Aprendizado de Máquina , Masculino , Satisfação do Paciente , Qualidade de Vida , Convulsões , Inquéritos e Questionários , Resultado do Tratamento
5.
Epilepsia ; 61(12): 2729-2738, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33063891

RESUMO

OBJECTIVE: No validated tools exist to assess satisfaction with epilepsy surgery. We aimed to develop and validate a new measure of patient satisfaction with epilepsy surgery, the 19-item Epilepsy Surgery Satisfaction Questionnaire (ESSQ-19). METHODS: An initial 31-item measure was developed based on literature review, patient focus groups, thematic analysis, and Delphi panels. The questionnaire was administered twice, 4-6 weeks apart, to 229 adults (≥18 years old) who underwent epilepsy surgery ≥1 year earlier, at three centers in Canada and one in Sweden. Participants also completed seven validated questionnaires to assess construct validity. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) assessed the factorial structure of the questionnaire. Cronbach alpha and intraclass correlation coefficients (ICCs) assessed the internal consistency and test-retest reliability of the ESSQ-19. Spearman and polyserial correlations assessed construct validity. RESULTS: Median age of participants and time since surgery were 42 years (interquartile range [IQR] = 32-54) and 5 years (IQR = 2-8.75), respectively. EFA and CFA yielded 18 items that segregated into four domains (mean score [SD]), namely, seizure control (76.4 [25]), psychosocial functioning (67.3 [26]), surgical complications (84 [22]), and recovery from surgery (73 [24]), one global satisfaction item, and a summary global score (74 [21]). The domain and summary scores demonstrated good to excellent internal reliability (Cronbach ⍺ range = .84-.95) and test-retest reliability (ICC range = 0.71-0.85). Construct validity was supported by predicted correlations with other instruments. SIGNIFICANCE: The ESSQ-19 is a new, valid, and reliable measure of patient satisfaction with epilepsy surgery that can be used in clinical and research settings.


Assuntos
Epilepsia/cirurgia , Satisfação do Paciente , Adulto , Análise Fatorial , Feminino , Humanos , Masculino , Satisfação do Paciente/estatística & dados numéricos , Reprodutibilidade dos Testes , Inquéritos e Questionários
6.
Int J Biol Macromol ; 138: 309-320, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31301397

RESUMO

Metacaspases are clan CD cysteine peptidases found in plants, fungi and protozoa that possess a conserved Peptidase_C14 domain, homologous to the human caspases and a catalytic His/Cys dyad. Earlier reports have indicated the role of metacaspases in cell death; however, metacaspases of human malaria parasite remains poorly understood. In this study, we aimed to functionally characterize a novel malarial protease, P. falciparum metacaspase-3 (PfMCA3). Unlike other clan CD peptidases, PfMCA3 has an atypical active site serine (Ser1865) residue in place of canonical cysteine and it phylogenetically forms a distinct branch across the species. To investigate whether this domain retains catalytic activity, we expressed, purified and refolded the Peptidase_C14 domain of PfMCA3 which was found to express in all asexual stages. PfMCA3 exhibited trypsin-like serine protease activity with ser1865 acting as catalytic residue to cleave trypsin oligopeptide substrate. PfMCA3 is inhibited by trypsin-like serine protease inhibitors. Our study found that PfMCA3 enzymatic activity was abrogated when catalytic serine1865 (S1865A) was mutated. Moreover, PfMCA3 was found to be inactive against caspase substrate. Overall, our study characterizes a novel metacaspase of P. falciparum, different from human caspases and not responsible for the caspase-like activity, therefore, could be considered as a potential chemotherapeutic target.


Assuntos
Caspases/metabolismo , Plasmodium falciparum/enzimologia , Serina Endopeptidases/metabolismo , Sequência de Aminoácidos , Biocatálise , Inibidores de Caspase/farmacologia , Caspases/química , Caspases/genética , Domínio Catalítico , Concentração de Íons de Hidrogênio , Cinética , Plasmodium falciparum/genética , Temperatura
7.
Acta Crystallogr F Struct Biol Commun ; 75(Pt 5): 397-398, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31045570

RESUMO

The article by Sharma et al. [(2018), Acta Cryst. F74, 656-663] is corrected.

8.
Exp Parasitol ; 197: 43-50, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30648557

RESUMO

Falcipain-2 (FP2) and falcipain-3 (FP3) constitute the major hemoglobinases of Plasmodium falciparum. Previous biochemical and structural studies have explained the mechanism of inhibition of these enzymes by small molecules. However, a residue-level protein-protein interaction (PPI) with its natural macromolecular substrate, hemoglobin is not fully characterized. Earlier studies have identified a short motif in the C-terminal of FP2, an exosite protruding away from the active site, essential for hemoglobin degradation. Our structural and mutagenesis studies suggest that hemoglobin interacts with FP2 via specific interactions mediated by Glu185 and Val187 within the C-terminal motif, which are essential for hemoglobin binding. Since FP3 is also a major hemoglobinase and essential for parasite survival, we further demonstrate its interactions with hemoglobin. Our results suggest that Asp194 of FP3 is required for hemoglobin hydrolysis and residue-swap experiments confirmed that this position is functionally conserved between the two hemoglobinases. Residues involved in protein-protein interactions constitute important targets for drug-mediated inhibition. Targeting protein-protein interactions at exosites may likely be less susceptible to emergence of drug resistance and thus is a new field to explore in malaria.


Assuntos
Cisteína Endopeptidases/metabolismo , Hemoglobinas/metabolismo , Plasmodium falciparum/enzimologia , Ácido Aspártico/química , Clonagem Molecular , Cisteína Endopeptidases/química , Cisteína Endopeptidases/genética , Ácido Glutâmico/química , Hemoglobinas/química , Hidrólise , Estrutura Molecular , Mutagênese , Plasmodium falciparum/genética
9.
Acta Crystallogr F Struct Biol Commun ; 74(Pt 10): 656-663, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30279318

RESUMO

ERG3 (ETS-related gene) is a member of the ETS (erythroblast transformation-specific) family of transcription factors, which contain a highly conserved DNA-binding domain. The ETS family of transcription factors differ in their binding to promoter DNA sequences, and the mechanism of their DNA-sequence discrimination is little known. In the current study, crystals of the ETSi domain (the ETS domain of ERG3 containing a CID motif) in space group P41212 and of its complex with the E74 DNA sequence (DNA9) in space group C2221 were obtained and their structures were determined. Comparative structure analysis of the ETSi domain and its complex with DNA9 with previously determined structures of the ERGi domain (the ETS domain of ERG containing inhibitory motifs) in space group P65212 and of the ERGi-DNA12 complex in space group P41212 were performed. The ETSi domain is observed as a homodimer in solution as well as in the crystallographic asymmetric unit. Superposition of the structure of the ETSi domain on that of the ERGi domain showed a major conformational change at the C-terminal DNA-binding autoinhibitory (CID) motif, while minor changes are observed in the loop regions of the ETSi-domain structure. The ETSi-DNA9 complex in space group C2221 forms a structure that is quite similar to that of the ERG-DNA12 complex in space group P41212. Upon superposition of the complexes, major conformational changes are observed at the 5' and 3' ends of DNA9, while the conformation of the core GGA nucleotides was quite conserved. Comparison of the ETSi-DNA9 structure with known structures of ETS class 1 protein-DNA complexes shows the similarities and differences in the promoter DNA binding and specificity of the class 1 ETS proteins.


Assuntos
Proteínas de Ligação a DNA/química , DNA/química , Proteína Proto-Oncogênica c-fli-1/química , Fatores de Transcrição/química , Sequência de Aminoácidos , Animais , Sítios de Ligação , Clonagem Molecular , Cristalografia por Raios X , DNA/genética , DNA/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Drosophila , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Humanos , Modelos Moleculares , Conformação de Ácido Nucleico , Regiões Promotoras Genéticas , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Multimerização Proteica , Proteína Proto-Oncogênica c-fli-1/genética , Proteína Proto-Oncogênica c-fli-1/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
10.
Mol Biochem Parasitol ; 220: 28-41, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29317266

RESUMO

Earlier studies on Plasmodium apoptosis revealed the presence of proteases with caspases like- activity, which are known as "metacaspases". Although this family of cysteine proteases is structurally similar to caspases with Cys-His dyad but their evolutionary significance and functional relevance remains largely unknown. These proteases are considered to be an important target against malaria due to their absence in humans. In this report, we have biochemically characterized metacaspase-2 (PfMCA-2) of P.falciparum. Enzymatic assay showed that PfMCA-2 efficiently cleaved arginine/lysine specific peptide, but not caspase-specific substrate. Consistently, PfMCA-2 activity was sensitive to effector caspases inhibitor, Z-FA-FMK, and mildly inhibited by aprotinin and E-64. However, general caspase inhibitors such as Z-VAD-FMK and Z-DEVD-FMK had no effect on PfMCA-2 activity. Z-FA-FMK inhibits parasite growth with an IC50 value of 2.7 µM along with the notable morphological changes. PfMCA-2 specifically expressed in schizonts and gametocyte stages and there was a notable depletion of PfMCA-2 expression in Z-FA-FMK treated schizonts and gametocytes stages of parasite. Notably, PfMCA-2 cleaves a phylogenetically conserved protein, TSN (Tudor staphylococcal nuclease) and the proteolysis of PfTSN did not occur after treatment with the Z-FA-FMK. The production of large amount of reactive oxygen species in presence of Z-FA-FMK caused oxidative stress which in turn leads to loss of cell viability. The oxidative stress further generates positive feedback for the occurrence of cell death in term of phosphatidylserine externalization and DNA fragmentation in vitro.


Assuntos
Cisteína Proteases/metabolismo , Plasmodium falciparum/enzimologia , Inibidores de Cisteína Proteinase/metabolismo , Dipeptídeos/metabolismo , Perfilação da Expressão Gênica , Cetonas/metabolismo , Leucina/análogos & derivados , Leucina/metabolismo , Plasmodium falciparum/crescimento & desenvolvimento , Especificidade por Substrato
11.
J Addict Med ; 11(3): 235-236, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28166085

RESUMO

: Here we describe a case of subacute combined spinal cord degeneration caused by nitrous oxide (N2O, laughing gas) use. Because of its euphoric effects, the use of N2O has become increasingly popular in recent years. Unfortunately, the use of N2O leads to inactivation of vitamin B12. Vitamin B12 plays an essential role in the synthesis and maintenance of myelin, a fatty substance that surrounds nerve cells and is crucial for their functioning. Deficiency of vitamin B12 could typically result in degeneration of posterior and lateral columns of the spinal cord. Treatment with intramuscular vitamin B12 injections and abstinence of N2O generally leads to gradual improvement of symptoms. Our case demonstrates the importance of the methyl malonic acid test to detect early or mild vitamin B12 deficiency as a cause of myelopathy while serum vitamin B12 level may be normal. Written consent was obtained from our patient to publish the details of this individual case.


Assuntos
Anestésicos Inalatórios/toxicidade , Óxido Nitroso/toxicidade , Degeneração Combinada Subaguda/induzido quimicamente , Degeneração Combinada Subaguda/diagnóstico , Adulto , Humanos , Masculino
12.
Leuk Res Rep ; 4(1): 36-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26052501

RESUMO

Pregnancy in women with paroxysmal nocturnal hemoglobinuria (PNH) is associated with increased maternal and fetal morbidity and mortality. There is limited published experience regarding therapy of PNH during pregnancy. We describe a case of a 30 year old female with hypoplastic myelodysplastic syndrome and PNH. After two years of treatment with eculizumab, she became pregnant. She developed breakthrough hemolysis at 20 weeks gestation. Pharmacokinetic and pharmacodynamic studies demonstrated a subtherapeutic eculizumab level with absence of complement blockade. Escalation of her eculizumab dose successfully controlled hemolysis and restored therapeutic eculizumab level and activity. She delivered a healthy baby at 36 weeks.

13.
PLoS One ; 9(4): e93008, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24699522

RESUMO

Cysteine proteases play a crucial role in the development of the human malaria parasites Plasmodium falciparum and Plasmodium vivax. Our earlier studies demonstrated that these enzymes are equipped with specific domains for defined functions and further suggested the mechanism of activation of cysteine proteases. The activities of these proteases are regulated by a new class of endogenous inhibitors of cysteine proteases (ICPs). Structural studies of the ICPs of Trypanosoma cruzi (chagasin) and Plasmodium berghei (PbICP) indicated that three loops (termed BC, DE, and FG) are crucial for binding to target proteases. Falstatin, an ICP of P. falciparum, appears to play a crucial role in invasion of erythrocytes and hepatocytes. However, the mechanism of inhibition of cysteine proteases by falstatin has not been established. Our study suggests that falstatin is the first known ICP to function as a multimeric protein. Using site-directed mutagenesis, hemoglobin hydrolysis assays and peptide inhibition studies, we demonstrate that the BC loop, but not the DE or FG loops, inhibits cysteine proteases of P. falciparum and P. vivax via hydrogen bonds. These results suggest that the BC loop of falstatin acts as a hot-spot target for inhibiting malarial cysteine proteases. This finding suggests new strategies for the development of anti-malarial agents based on protease-inhibitor interactions.


Assuntos
Cisteína Proteases/metabolismo , Inibidores de Cisteína Proteinase/metabolismo , Eritrócitos/parasitologia , Malária Falciparum/parasitologia , Plasmodium falciparum/enzimologia , Plasmodium falciparum/patogenicidade , Proteínas de Protozoários/metabolismo , Sequência de Aminoácidos , Reações Cruzadas , Cisteína Proteases/química , Eritrócitos/patologia , Hemoglobinas/metabolismo , Humanos , Ligação de Hidrogênio , Hidrólise , Malária Falciparum/patologia , Modelos Moleculares , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Mutação/genética , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/metabolismo , Plasmodium falciparum/genética , Conformação Proteica , Multimerização Proteica , Proteínas de Protozoários/química , Proteínas de Protozoários/genética , Homologia de Sequência de Aminoácidos
14.
J Biol Chem ; 285(34): 26532-44, 2010 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-20479005

RESUMO

Because pure cultures and a stable transformation system are not available for arbuscular mycorrhizal fungi, the role of their phosphate transporters for the symbiotic interaction with the plant up till now could not be studied. Here we report the cloning and the functional analysis of a gene encoding a phosphate transporter (PiPT) from the root endophytic fungus Piriformospora indica, which can be grown axenically. The PiPT polypeptide belongs to the major facilitator superfamily. Homology modeling reveals that PiPT exhibits twelve transmembrane helices divided into two halves connected by a large hydrophilic loop in the middle. The function of the protein encoded by PiPT was confirmed by complementation of a yeast phosphate transporter mutant. The kinetic analysis of PiPT (K(m) 25 mum) reveals that it belongs to the high affinity phosphate transporter family (Pht1). Expression of PiPT was localized to the external hyphae of P. indica colonized with maize plant root, which suggests that external hyphae are the initial site of phosphate uptake from the soil. To understand the physiological role of PiPT, knockdown transformants of the gene were prepared using electroporation and RNA interference. Knockdown transformants transported a significantly lower amount of phosphate to the host plant than wild-type P. indica. Higher amounts of phosphate were found in plants colonized with wild-type P. indica than that of non-colonized and plants colonized with knockdown PiPT P. indica. These observations suggest that PiPT is actively involved in the phosphate transportation and, in turn, P. indica helps improve the nutritional status of the host plant.


Assuntos
Basidiomycota/química , Proteínas de Transporte de Fosfato/metabolismo , Fosfatos/metabolismo , Raízes de Plantas/microbiologia , Simbiose/fisiologia , Transporte Biológico , Clonagem Molecular , Genes Fúngicos/genética , Hifas , Cinética , Conformação Proteica , Zea mays/microbiologia
15.
Conn Med ; 73(6): 341-3, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19637664

RESUMO

Primary squamous cell carcinoma of the breast (PSCCB) is a rare and generally aggressive malignancy constituting < 0.1% of invasive breast cancers. This report describes a case of primary squamous cell carcinoma of the breast that emerged in association with a phyllodes tumor. Our patient, a 59-year-old female, presented with a rapidly growing 9x12 cm breast mass. She underwent modified radical mastectomy followed by chemotherapy with carboplatin and docetaxel. She is free of disease one year after diagnosis. Clinicians should be aware of the aggressive behavior of this tumor, and adequate investigation should be done to rule out metastasis from another primary site.


Assuntos
Neoplasias da Mama/patologia , Carcinoma de Células Escamosas/patologia , Tumor Filoide/patologia , Neoplasias da Mama/cirurgia , Carcinoma de Células Escamosas/cirurgia , Feminino , Humanos , Imuno-Histoquímica , Mastectomia Radical Modificada , Pessoa de Meia-Idade
16.
Clin Breast Cancer ; 9(1): 53-5, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19299242

RESUMO

Bowen's disease, or squamous cell carcinoma in situ (SCCIS) of the skin, is a malignant neoplasm restricted to the epidermis, without evidence of dermal invasion. It usually develops in sun-exposed area of skin, but other sites can also be affected. Bowen's disease of the nipple is extremely rare and has thus far been reported only in women. We present the case of Bowen's disease of the nipple in an HIV-positive male patient who presented with a scaly lesion on nipple for one year. He also had past genital infection with human papillomavirus, but he was found to be negative for high-risk subtypes. Biopsy of the lesion revealed SCCIS of the nipple areola complex, with extension into the underlying lactiferous ducts of the breast. There was no evidence of invasive carcinoma. The patient was treated with a simple mastectomy with sentinel lymph node biopsy. With the advent of highly active antiretroviral treatment, chronic non-HIV related conditions have become more important, male breast cancer being one of them. To the best of our knowledge, this is the first reported case in the worldwide literature of Bowen's disease of the nipple in a young immunocompromised male patient. More aggressive therapy in HIV-positive male patients presenting with precancerous and cancerous breast lesions is recommended.


Assuntos
Doença de Bowen/etiologia , Neoplasias da Mama Masculina/patologia , Infecções por HIV/complicações , Mamilos/patologia , Adulto , Doença de Bowen/tratamento farmacológico , Neoplasias da Mama Masculina/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Soropositividade para HIV , Humanos , Masculino , Mamilos/efeitos dos fármacos , Prognóstico
17.
Skeletal Radiol ; 37(9): 805-11, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18566813

RESUMO

PURPOSE: The purpose of the study was to relate magnetic resonance imaging (MRI) features at baseline with radiographically determined joint space narrowing (JSN) in the medial compartment of the knee after 2 years in a group of patients with symptomatic osteoarthritis at multiple joint sites. MATERIALS AND METHODS: MRI of the knee and standardized radiographs were obtained at baseline and after 2 years in 186 patients (81% female; aged 43-76 years; mean 60 years). MRI was analyzed for bone marrow lesions, cysts, osteophytes, hyaline cartilage defects, joint effusion, and meniscal pathology in the medial compartment. Radiographs were scored semiquantitatively for JSN in the medial tibiofemoral joint using the Osteoarthritis Research Society International (OARSI) atlas. Radiological progression was defined as > or =1 grade increase. Associations between baseline magnetic resonance (MR) parameters and subsequent radiographic JSN changes were assessed using logistic regression. Relative risk (RR) was then calculated. RESULTS: Radiographic progression of JSN was observed in 17 (9.1%) of 186 patients. Eleven patients had a Kellgren and Lawrence (KL) score of > or =2. A significant association was observed between all patients and meniscal tears (RR 3.57; confidence interval (CI) 1.08-10.0) and meniscal subluxation (RR 2.73; CI 1.20-5.41), between KL < 2 and meniscal subluxation (RR 11.3; CI 2.49-29.49) and KL > or = 2 and meniscus tears (RR 8.91; CI 1.13-22.84) and radiographic JSN 2 years later. Follow-up MR in 15 of 17 patients with progressive JSN showed only new meniscal abnormalities and no progression of cartilage loss. CONCLUSION: Meniscal pathology (tears and/or meniscal subluxation) was the only MRI parameter to be associated with subsequent radiographic progression of JSN in the medial tibiofemoral compartment on a radiograph 2 years later, as assessed by the OARSI score.


Assuntos
Imageamento por Ressonância Magnética/métodos , Osteoartrite do Joelho/patologia , Adulto , Idoso , Progressão da Doença , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/patologia , Modelos Logísticos , Masculino , Meniscos Tibiais/diagnóstico por imagem , Meniscos Tibiais/patologia , Pessoa de Meia-Idade , Osteoartrite do Joelho/diagnóstico por imagem , Valor Preditivo dos Testes , Radiografia
18.
Eur Radiol ; 17(12): 3073-8, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17823802

RESUMO

It has been suggested that bone marrow edema-like (BME) lesions in the knee are associated with progression of osteoarthritis (OA). The purpose of our study in patients with OA was to evaluate prospectively changes of BME lesions over 2 years and their relationship with clinical features. Magnetic resonance (MR) images of the knee were obtained from 182 patients (20% male; aged 43-76 years; mean age 59 years) who had been diagnosed with familial symptomatic OA at multiple joint sites. MR images were made at baseline and at 2 years follow-up. BME lesions in 2 years were associated with clinical features assessed by Western Ontario and McMaster Universities Osteoarthritis (WOMAC) scores. A total of 327 BME lesions were recorded. Total size of BME lesions changed in 90 patients (66%). Size of individual lesions changed in 147 foci (45%): new lesions appeared in 69 (21%), existing lesions disappeared in 32 (10%), increased in size in 26 (8%) and decreased in size in 20 (6%) lesions. Increase or decrease of BME lesions, over a 2-year time period, was not associated with severity of WOMAC scores. BME lesions fluctuated in the majority of patients with OA over a 2-year time period. These changes were not associated with severity of WOMAC scores at the study end point.


Assuntos
Doenças da Medula Óssea/patologia , Edema/patologia , Imageamento por Ressonância Magnética/métodos , Osteoartrite do Joelho/patologia , Adulto , Idoso , Intervalos de Confiança , Progressão da Doença , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Prospectivos , Fatores de Tempo
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