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1.
Am J Physiol Endocrinol Metab ; 319(5): E923-E931, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32954827

RESUMO

The pathophysiology and time course of impairment in cutaneous microcirculatory function and structure remain poorly understood in people with diabetes, partly due to the lack of investigational tools capable of directly imaging and quantifying the microvasculature in vivo. We applied a new optical coherence tomography (OCT) technique, at rest and during reactive hyperemia (RH), to assess the skin microvasculature in people with diabetes with foot ulcers (DFU, n = 13), those with diabetes without ulcers (DNU, n = 9), and matched healthy controls (CON, n = 13). OCT images were obtained from the dorsal part of the foot at rest and following 5 min of local ischemia induced by inflating a cuff around the thigh at suprasystolic level (220 mmHg). One-way ANOVA was used to compare the OCT-derived parameters (diameter, speed, flow rate, and density) at rest and in response to RH, with repeated-measures two-way ANOVA performed to analyze main and interaction effects between groups. Data are means ± SD. At rest, microvascular diameter in the DFU (84.89 ± 14.84 µm) group was higher than CON (71.25 ± 7.6 µm, P = 0.012) and DNU (71.33 ± 12.04 µm, P = 0.019) group. Speed in DFU (65.56 ± 4.80 µm/s, P = 0.002) and DNU (63.22 ± 4.35 µm/s, P = 0.050) were higher than CON (59.58 ± 3.02 µm/s). Microvascular density in DFU (22.23 ± 13.8%) was higher than in CON (9.83 ± 2.94%, P = 0.008), but not than in the DNU group (14.8 ± 10.98%, P = 0.119). All OCT-derived parameters were significantly increased in response to RH in the CON group (all P < 0.01) and DNU group (all P < 0.05). Significant increase in the DFU group was observed in speed (P = 0.031) and density (P = 0.018). The change in density was lowest in the DFU group (44 ± 34.1%) compared with CON (199.2 ± 117.5%, P = 0.005) and DNU (148.1 ± 98.4, P = 0.054). This study proves that noninvasive OCT microvascular imaging is feasible in people with diabetes, provides powerful new physiological insights, and can distinguish between healthy individuals and patients with diabetes with distinct disease severity.


Assuntos
Diabetes Mellitus Tipo 2/diagnóstico por imagem , Pé Diabético/diagnóstico por imagem , Microvasos/diagnóstico por imagem , Pele/irrigação sanguínea , Idoso , Feminino , Humanos , Hiperemia/diagnóstico por imagem , Masculino , Microcirculação , Pessoa de Meia-Idade , Pele/diagnóstico por imagem , Tomografia de Coerência Óptica
2.
J Vasc Interv Radiol ; 29(5): 623-627, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29685659

RESUMO

This report presents 3 procedures with visceral "chimney stenting" in conjunction with an endovascular aneurysm sealing (EVAS) device, known as chEVAS, for treatment of type 1a endoleak. It includes the first published chEVAS in a patient with previous fenestrated endovascular aneurysm repair (FEVAR). Cases include an 80-year-old man 8 years after FEVAR for a juxtarenal abdominal aortic aneurysm (AAA); an 85-year-old woman 9 months after endovascular aneurysm repair (EVAR) for a ruptured infrarenal AAA; and an 84-year-old woman 3 months after EVAR for a symptomatic infrarenal AAA. Technical success was achieved in all cases, with 1 postoperative death. The remaining 2 patients had no residual type 1a endoleak at 10 and 14 months respectively.


Assuntos
Aneurisma Roto/cirurgia , Aneurisma da Aorta Abdominal/cirurgia , Endoleak/cirurgia , Procedimentos Endovasculares/métodos , Complicações Pós-Operatórias/cirurgia , Stents , Idoso de 80 Anos ou mais , Angiografia , Evolução Fatal , Feminino , Humanos , Masculino , Estudos Retrospectivos
3.
Nephrology (Carlton) ; 22 Suppl 1: 18-22, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28176472

RESUMO

BACKGROUND: Atypical haemolytic uraemic syndrome (aHUS) is a rare condition with the triad of microangiopathic haemolytic anaemia, thrombocytopenia and acute kidney injury. Other conditions that present in a similar manner peri-partum include thrombotic thrombocytopaenic purpura, and pregnancy associated conditions including HELLP syndrome (haemolysis, elevated liver enzymes and low platelets), severe pre-eclampsia and less commonly acute fatty liver of pregnancy. CASE REPORTS: We describe two cases of suspected aHUS, who presented post-partum with foetal death-in-utero at 33 and 37 weeks respectively. Both presented with the triad features of aHUS but had considerably different clinical courses. The first case required a prolonged ICU admission, needed intubation for neurological deterioration and dialysis for acute kidney injury, and developed complications including acute liver failure, septic shock, pancreatitis, and ischaemic colitis. Initial ADAMSTS13 activity was borderline-low (10.3%) and normal on repeat testing (42.6%), and there was no peri-partum pre-eclampsia. The other case remained clinically stable throughout her admission with creatinine peaking at 495, not requiring dialysis, minor liver transaminases derangement and was discharged after a week. Her ADAMSTS13 activity was normal (62%), and her pregnancy was complicated by peri-partum pre-eclampsia. Both eventually had a reduction in haemolysis with rapid and sustained reduction in LDH and normalised platelet counts, and complete recovery of renal function whilst receiving eculizumab therapy. CONCLUSIONS: It can be difficult to distinguish aHUS from other causes in peri-partum patients presenting with features of microangiopathic haemolytic anaemia, thrombocytopenia and acute kidney injury, and often, aHUS can be precipitated by pregnancy. In the setting of the clinical urgency to treat aHUS early with eculizumab, this presents a diagnostic challenge, as confirmatory tests for aHUS are not immediately available.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Morte Fetal/etiologia , Transtornos Puerperais/tratamento farmacológico , Adulto , Síndrome Hemolítico-Urêmica Atípica/complicações , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Feminino , Humanos , Gravidez , Transtornos Puerperais/diagnóstico , Transtornos Puerperais/etiologia
4.
Neoplasma ; 62(4): 627-34, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25997970

RESUMO

Very few studies have determined the prognostic value of interim and restaging PET/CT in patients with Hodgkin lymphoma using current standard of care therapy outside clinical trials. We analyzed the effect of the results of interim and restaging PET/CT on the survival (overall- and relapse-free) in patients who received standard first-line treatment based on the stage of disease and risk factors. We investigated the differences between the relapse and non-relapse groups based on the clinical pathological characteristics of patients who had positive interim PET/CT results.Between January 1, 2007 and December 31, 2011, the staging, interim and restaging PET/CT scans of patients with Hodgkin lymphoma were analyzed. The Deauville criteria were used for the evaluation of interim PET/CT scans. One hundred and thirteen Hodgkin lymphoma patients underwent staging, interim and restaging PET/CT scans. None of the therapy was modified based on the interim PET/CT results. The median follow-up time was 43.5 months. A total of 62 early stage patients and 51 advanced stage patients were identified. The five-year overall survival rates were 93.4% in the interim PET negative group and 58% in the interim PET positive group (p<0.001). The five-year relapse-free survival rates for the negative and positive groups were 92.7% and 40.8%, respectively (p<0.001). The negative predictive value was 100% in the early stage group and 82.35% in the advanced stage group. By comparison, the positive predictive values were 53.8% and 58.8%, respectively, in these two groups. In the interim PET positive group, patients over 40 years of age had a significantly higher probability of relapse (p=0.057).The routine clinical use of interim PET/CT is highly recommended based on our investigation. However, patients with positive interim PET/CT results required frequent additional evaluations.

5.
Acta Neuropathol ; 128(4): 597-604, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24718895

RESUMO

Polyglutamine expansions in the ataxin-2 gene (ATXN2) cause autosomal dominant spinocerebellar ataxia type 2 (SCA2), but have recently also been associated with amyotrophic lateral sclerosis (ALS). We present clinical and pathological features of a family in which a pathological ATXN2 expansion led to frontotemporal lobar degeneration with ALS (FTLD-ALS) in the index case, but typical SCA2 in a son, and compare the neuropathology with a case of typical SCA2. The index case shares the molecular signature of SCA2 with prominent polyglutamine and p62-positive intranuclear neuronal inclusions mainly in the pontine nuclei, while harbouring more pronounced neocortical and spinal TDP-43 pathology. We conclude that ATXN2 mutations can cause not only ALS, but also a neuropathological overlap syndrome of SCA2 and FTLD presenting clinically as pure FTLD-ALS without ataxia. The cause of the phenotypic heterogeneity remains unexplained, but the presence of a CAA-interrupted CAG repeat in the FTLD case in this family suggests that one potential mechanism may be variation in repeat tract composition between members of the same family.


Assuntos
Esclerose Lateral Amiotrófica/complicações , Esclerose Lateral Amiotrófica/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas do Tecido Nervoso/genética , Ataxias Espinocerebelares/complicações , Ataxias Espinocerebelares/genética , Idoso de 80 Anos ou mais , Esclerose Lateral Amiotrófica/patologia , Ataxinas , Análise Mutacional de DNA , Saúde da Família , Humanos , Masculino , Ataxias Espinocerebelares/patologia , Expansão das Repetições de Trinucleotídeos
6.
Clin Ther ; 45(11): 1069-1076, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37770311

RESUMO

PURPOSE: Extracranial atherosclerotic carotid stenosis is associated with inadequate cerebral blood flow (CBF) and cognitive dysfunction. The impact of extracranial carotid revascularization on cognition and how any cognitive change relates to changes in CBF are less clear. This review examines the effects of revascularization of extracranial carotid disease by carotid endarterectomy (CEA) or carotid stenting (CAS) on cognition, and how this relates to changes in CBF. METHODS: A systematic review of existing reports in the Medline, Embase, and Cochrane databases was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement recommendations. All original retrospective or prospective studies and clinical trials that compared pre- and postoperative cognitive function and CBF in patients with extracranial carotid stenosis who underwent CEA or CAS versus a control group, published between January 1985 and December 2022, were identified and considered eligible for inclusion in this study. FINDINGS: Seven studies (661 participants; 460 CEA or CAS) were identified. All were observational studies and of moderate to good methodologic quality. Six studies (619 participants; follow-up range 1 month to 2 years) demonstrated improvement in some cognitive domains following CEA or CAS, improvement in CBF following revascularization, and correlated some of these cognitive changes with changes in CBF. One study (42 participants; 3 months follow-up) found cognitive improvement following CEA, but found no improvement in CBF or any correlation between cognitive and CBF change. The literature however represented heterogenous study populations examining asymptomatic and/or symptomatic carotid stenosis, differing in treatment modality and criteria for control groups ranging from healthy volunteers to those with stenosis but not who underwent surgical revascularization, and finally, differing reporting methods. This heterogeneity precluded meta-analysis. IMPLICATIONS: Definitive conclusions are limited by variation in cognitive function assessment, timing of testing, and how these are correlated to CBF. However, research suggests a potential improvement in cognition which may be associated with improvement in CBF, particularly in those patients who have more significant CBF deficit at baseline. Further studies are required to better understand this association and provide a clearer picture of the cognitive effects of carotid revascularization.


Assuntos
Doenças das Artérias Carótidas , Estenose das Carótidas , Endarterectomia das Carótidas , Humanos , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/cirurgia , Estenose das Carótidas/complicações , Estudos Prospectivos , Estudos Retrospectivos , Endarterectomia das Carótidas/efeitos adversos , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/cirurgia , Doenças das Artérias Carótidas/complicações , Cognição , Circulação Cerebrovascular/fisiologia , Stents , Resultado do Tratamento
7.
Front Immunol ; 14: 1158905, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37313411

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces B and T cell responses, contributing to virus neutralization. In a cohort of 2,911 young adults, we identified 65 individuals who had an asymptomatic or mildly symptomatic SARS-CoV-2 infection and characterized their humoral and T cell responses to the Spike (S), Nucleocapsid (N) and Membrane (M) proteins. We found that previous infection induced CD4 T cells that vigorously responded to pools of peptides derived from the S and N proteins. By using statistical and machine learning models, we observed that the T cell response highly correlated with a compound titer of antibodies against the Receptor Binding Domain (RBD), S and N. However, while serum antibodies decayed over time, the cellular phenotype of these individuals remained stable over four months. Our computational analysis demonstrates that in young adults, asymptomatic and paucisymptomatic SARS-CoV-2 infections can induce robust and long-lasting CD4 T cell responses that exhibit slower decays than antibody titers. These observations imply that next-generation COVID-19 vaccines should be designed to induce stronger cellular responses to sustain the generation of potent neutralizing antibodies.


Assuntos
COVID-19 , Humanos , Vacinas contra COVID-19 , SARS-CoV-2 , Anticorpos Neutralizantes , Aprendizado de Máquina
8.
Parasite ; 18(3): 277-80, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21894270

RESUMO

The natural transmission of dengue virus from an infected female mosquito to its progeny, namely the vertical transmission, was researched in wild caught Aedes aegypti during an important outbreak in the town of Santa Cruz de la Sierra, Bolivia. Mosquitoes were collected at the preimaginal stages (eggs, larvae and pupae) then reared up to adult stage for viral detection using molecular methods. Dengue virus serotypes 1 and 3 were found to be co-circulating with significant higher prevalence in male than in female mosquitoes. Of the 97 pools of Ae. aegypti (n = 635 male and 748 female specimens) screened, 14 pools, collected in February-May in 2007, were found positive for dengue virus infection: five DEN-1 and nine DEN-3. The average true infection rate (TIR) and minimum infection rate (MIR) were respectively 1.08% and 1.01%. These observations suggest that vertical transmission of dengue virus may be detected in vectors at the peak of an outbreak as well as several months before an epidemic occurs in human population.


Assuntos
Aedes/virologia , Vírus da Dengue/fisiologia , Dengue/transmissão , Insetos Vetores/virologia , Animais , Bolívia/epidemiologia , Dengue/epidemiologia , Surtos de Doenças , Feminino , Masculino , Fatores Sexuais
9.
Neoplasma ; 57(4): 349-54, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20429626

RESUMO

Determining the viability of residual tumor masses is a great challenge after primary treatment of Hodgkin lymphoma. FDG-PET may play a crucial role in this procedure. In this study, files of 128 Hodgkin lymphoma patients were reviewed, who were treated in three Hungarian hematology centers between January 1995 and February 2005. CT scan showed residual tumor mass by all of them. Their median follow-up was 75.5 months from PET examination. The number of true-positive, true-negative, false-positive, false-negative subjects were 29, 83, 10, 6, respectively. Sensitivity of post-treatment FDG-PET was 83 %, specificity 93 %, positive predictive value 74 %, negative predictive value 93 %, and accuracy 88 %. The difference between the event free survival of PET positive and negative cases is highly significant (p=0.0000), according to the Mantel-Cox test. Our results in the largest cohort of patients, in accordance with literature, clearly indicates that patients with negative FDG-PET results are unlikely to progress or relapse during the longest follow-up.


Assuntos
Fluordesoxiglucose F18 , Doença de Hodgkin/diagnóstico por imagem , Recidiva Local de Neoplasia/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Adolescente , Adulto , Idoso , Estudos de Coortes , Reações Falso-Negativas , Reações Falso-Positivas , Feminino , Seguimentos , Doença de Hodgkin/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/terapia , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Sensibilidade e Especificidade , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
10.
Artigo em Inglês | MEDLINE | ID: mdl-32847842

RESUMO

INTRODUCTION: The pathophysiology of microvascular disease is poorly understood, partly due to the lack of tools to directly image microvessels in vivo. RESEARCH DESIGN AND METHODS: In this study, we deployed a novel optical coherence tomography (OCT) technique during local skin heating to assess microvascular structure and function in diabetics with (DFU group, n=13) and without (DNU group, n=10) foot ulceration, and healthy controls (CON group, n=13). OCT images were obtained from the dorsal foot, at baseline (33°C) and 30 min following skin heating. RESULTS: At baseline, microvascular density was higher in DFU compared with CON (21.9%±11.5% vs 14.3%±5.6%, p=0.048). Local heating induced significant increases in diameter, speed, flow rate and density in all groups (all p<0.001), with smaller changes in diameter for the DFU group (94.3±13.4 µm), compared with CON group (115.5±11.7 µm, p<0.001) and DNU group (106.7±12.1 µm, p=0.014). Heating-induced flow rate was lower in the DFU group (584.3±217.0 pL/s) compared with the CON group (908.8±228.2 pL/s, p<0.001) and DNU group (768.8±198.4 pL/s, p=0.014), with changes in density also lower in the DFU group than CON group (44.7%±15.0% vs 56.5%±9.1%, p=0.005). CONCLUSIONS: This proof of principle study indicates that it is feasible to directly visualize and quantify microvascular function in people with diabetes; and distinguish microvascular disease severity between patients.


Assuntos
Diabetes Mellitus , Tomografia de Coerência Óptica , Humanos , Microvasos/diagnóstico por imagem , Pele/diagnóstico por imagem
11.
Am J Hematol ; 84(11): 715-9, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19806661

RESUMO

To identify patients who developed secondary clonal cytogenetic aberrations (CCA) following therapy for acute promyelocytic leukemia (APL), we retrospectively analyzed cytogenetic results from 123 patients diagnosed with APL between 1995 and 2007, who had ongoing cytogenetic analysis undertaken in our laboratory. During follow-up for APL we identified 12 patients (9.8%) who developed CCA, not detected at diagnosis of APL and unrelated to their original APL karyotype. All patients had received all-trans retinoic acid (ATRA) and chemotherapy and were in complete remission for APL when secondary CCA were identified. The median latency period between diagnosis of APL and emergence of secondary CCA was 27.5 months (range: 2-54 months). To date, four patients with CCA have been diagnosed with therapy-related myelodysplastic syndrome (t-MDS)/acute myeloid leukemia (t-AML), giving a median t-MDS/AML free survival of 78 months, with follow-up ranging between 20 and 136 months from APL diagnosis. Three patients have died: two patients died of t-AML and another developed relapsed APL with persistence of his secondary clone but no diagnosis of t-MDS/AML and died from transplant-related complications. Two patients are alive with t-MDS. Seven patients with CCA are alive with no morphological evidence of MDS at the time of their last known follow-up; thus median survival has not been reached. The appearance of these abnormalities in the absence of morphological evidence of MDS in the majority of patients is unusual, and highlights the importance of continued cytogenetic follow-up in these patients. Am. J. Hematol., 2009. (c) 2009 Wiley-Liss, Inc.


Assuntos
Aberrações Cromossômicas/induzido quimicamente , Leucemia Promielocítica Aguda/genética , Segunda Neoplasia Primária/induzido quimicamente , Tretinoína/uso terapêutico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica , Feminino , Humanos , Leucemia Mieloide Aguda/induzido quimicamente , Leucemia Mieloide Aguda/genética , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/induzido quimicamente , Síndromes Mielodisplásicas/genética , Segunda Neoplasia Primária/genética , Indução de Remissão/métodos , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
12.
Leuk Lymphoma ; 56(5): 1406-15, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25248882

RESUMO

Acute myeloid leukemia (AML) blasts express high levels of interlekin-3 (IL-3) receptor-α (CD123). CSL360 is a recombinant, chimeric immunoglobulin G1 (IgG1), anti-CD123 monoclonal antibody (MoAb) that neutralizes IL-3 and demonstrates anti-leukemic activity in vitro. This phase 1 study assessed safety, pharmacokinetics and bioactivity of weekly intravenous CSL360 for 12 weeks in 40 patients with advanced AML across five dose levels (0.1-10.0 mg/kg). Other than mild infusion reactions, CSL360 was well tolerated. The maximal tolerated dose was not reached. The half-life was 4.9 days, and the area under the curve (AUC) and maximum concentration (Cmax) increased proportionally with dose. Doses ≥ 3.0 mg/kg resulted in complete saturation and down-regulation of CD123 and abolition of ex vivo proliferative responsiveness to IL-3, indicating adequate blockade of IL-3 signaling. Two patients responded, with one remaining in complete remission after 17 doses. CSL360 bound CD123 specifically, but did not induce anti-leukemic activity in most patients. While safe, MoAb blockade of CD123 function is insufficient as a therapeutic strategy.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/farmacocinética , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Proliferação de Células/efeitos dos fármacos , Feminino , Regulação Leucêmica da Expressão Gênica , Humanos , Interleucina-3/metabolismo , Subunidade alfa de Receptor de Interleucina-3/antagonistas & inibidores , Subunidade alfa de Receptor de Interleucina-3/genética , Subunidade alfa de Receptor de Interleucina-3/metabolismo , Masculino , Pessoa de Meia-Idade , Recidiva , Resultado do Tratamento , Adulto Jovem
13.
Biochimie ; 85(1-2): 181-8, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12765787

RESUMO

Cell recognition and adhesion involving many kinds of cell surface molecules operate via homotypic and/or heterotypic protein-protein and protein-carbohydrate binding. Our investigations in marine sponges have provided direct evidence for a novel molecular mechanism of multivalent glycan-glycan binding related to cellular interactions. Biochemical characterization of purified proteoglycans revealed the presence of specific acidic glycans, different from classical glycosaminoglycans. Such acidic glycans of high molecular weight, containing fucose, glucuronic or galacturonic acids, and pyruvate and sulfate groups may represent a new class of primordial proteoglycans, named by us glyconectins. The thermodynamic and kinetic approaches of biological macromolecule interactions do not provide a direct measurement of the intermolecular binding forces that are fundamental for the function of the ligand-receptor association. Using the atomic force microscopy (AFM), we provided the first quantitative evaluation of the binding strength between cell adhesion proteoglycans. Measurement of binding forces intrinsic to cell adhesion glyconectin proteoglycans (AGPs) is necessary to assess their contribution to the maintenance of the anatomical integrity of multicellular organisms. (i) As a model, we selected the cell AGP isolated from the marine sponge Microciona prolifera; it mediates in vivo cell recognition and aggregation via homotypic, species-specific, multivalent, and calcium ion-dependent glycan-glycan interactions. (ii) Under physiological conditions, a large cohesive force theoretically able to hold the weight of approximately 1600 cells was measured. (iii) The C-2 autocomplementarity model for AGP-AGP interactions; and (iv) the requirement of the calcium ionic bridges suggest also that the self-recognition and multivalency of glycan-glycan interactions are essential for cell adhesion. (v) The evolution of glyconectin-like proteoglycan molecules may have been a fundamental prerequisite for the emergence of the first multicellular organisms. Glycan-glycan interactions may thus provide a new paradigm for molecular self-recognition.


Assuntos
Moléculas de Adesão Celular/química , Polissacarídeos/química , Poríferos/fisiologia , Proteoglicanas/química , Animais , Cálcio , Cátions Bivalentes , Moléculas de Adesão Celular/metabolismo , Fragmentos Fab das Imunoglobulinas/química , Fragmentos Fab das Imunoglobulinas/metabolismo , Magnésio , Microscopia de Força Atômica , Polissacarídeos/metabolismo , Poríferos/química , Proteoglicanas/metabolismo
14.
Chest ; 104(1): 317-8, 1993 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8325103

RESUMO

The occurrence of respiratory failure as a result of a large diaphragmatic hernia is a well-described entity in infants with congenital hernias. On reviewing the literature, the authors did not find a similar clinical presentation in the adult population. They report the case of an elderly patient with a large hiatus hernia who developed recurrent episodes of life-threatening respiratory failure and hemodynamic compromise due to recurrent gastric dilatation. Decompression with nasogastric suction resulted in dramatic and immediate relief of the respiratory distress. One should keep in mind the possibility of intrathoracic gastric dilatation as a cause of acute respiratory insufficiency in patients with hiatal hernia.


Assuntos
Dilatação Gástrica/complicações , Hérnia Diafragmática/complicações , Pneumotórax/etiologia , Insuficiência Respiratória/etiologia , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Feminino , Dilatação Gástrica/terapia , Humanos , Intubação Gastrointestinal
15.
Brain Res ; 934(1): 49-57, 2002 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-11937069

RESUMO

We used the highly selective 5-HT(6) receptor radioligand [(125)I]SB-258585 (4-iodo-N-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]benzene-sulfonamide) to perform autoradiographic binding studies on the rat brain. High levels of specific binding occurred in the corpus striatum, nucleus accumbens, Islands of Calleja and the olfactory tubercle. A high level of binding also appeared in the choroid plexus. Moderate levels occurred in several regions of the hippocampal formation and in certain regions of the cerebral cortex, thalamus, hypothalamus, and substantia nigra; and very low levels in the globus pallidus, cerebellum, other mesencephalic regions, and the rhombencephalon. Displacement of total binding with 10 microM unlabelled SB-214111 (4-bromo-N-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]benzene-sulfonamide), another selective 5-HT(6) receptor antagonist, or 10 microM unlabelled methiothepin, reduced binding to barely discernible levels. Some animals received unilateral injections of 6-hydroxydopamine (6-OHDA) into the median forebrain bundle to lesion the nigro-striatal pathway before autoradiographic examination. Effectiveness of the 6-OHDA lesions in the substantia nigra and striatum was confirmed with tyrosine hydroxylase immunohistochemistry. Such lesions resulted in no significant changes in [(125)I]SB-SB258585 binding in any brain region examined, suggesting that 5-HT(6) receptors in the striatum are not located on dendritic, somatic or terminal elements of dopaminergic neurones. Thus, the striatal binding sites seen in this study may be on intrinsic GABAergic or cholinergic neurones, or on terminals of projection neurones from the thalamus or cerebral cortex. The 5-HT(6) receptor ligand binding seen here in the striatum, accumbens, olfactory tubercle, Islands of Calleja, cerebral cortex and hippocampus are in concordance with previous immunohistochemical studies, and suggest a possible involvement of 5-HT(6) receptors in locomotor control, cognition, memory, and control of affect. The high levels of binding observed in the choroid plexus in this study have not been reported before. This finding suggests that 5-HT(6) receptors could play a role in the control of cerebrospinal fluid dynamics.


Assuntos
Encéfalo/metabolismo , Plexo Corióideo/metabolismo , Neurônios/metabolismo , Receptores de Serotonina/metabolismo , Serotonina/metabolismo , Animais , Autorradiografia , Sítios de Ligação/fisiologia , Encéfalo/citologia , Líquido Cefalorraquidiano/metabolismo , Plexo Corióideo/citologia , Denervação , Dopamina , Radioisótopos do Iodo , Masculino , Feixe Prosencefálico Mediano/efeitos dos fármacos , Feixe Prosencefálico Mediano/lesões , Feixe Prosencefálico Mediano/fisiopatologia , Neostriado/citologia , Neostriado/metabolismo , Vias Neurais/citologia , Vias Neurais/metabolismo , Neurônios/citologia , Oxidopamina/farmacologia , Piperazinas , Ensaio Radioligante , Ratos , Ratos Sprague-Dawley , Antagonistas da Serotonina , Substância Negra/citologia , Substância Negra/metabolismo , Sulfonamidas , Simpatolíticos/farmacologia , Tirosina 3-Mono-Oxigenase/metabolismo
16.
Neoplasma ; 27(3): 261-9, 1980.
Artigo em Inglês | MEDLINE | ID: mdl-7453846

RESUMO

A series of 31 aromatic nitrogen mustards was treated by means of the Minimal Tropological Difference (MTD)-receptor site mapping procedure by respect to toxicity (LD50) and efficacy (TGI%) against Jensen sarcoma. The correlation equations obtained for the two cases are: (Formula: see text), The low correlation coefficients indicate a not too high dependence upon steric factors of TGI% and LD50. However these results suggested that: a) the ortho-substitution represents a favorable event for both toxicity and antitumor effectiveness (j = 1 and 18 being good vertices in both corresponding hypermolecules), b) despite this effect, the steric features involved in these two biologic parameters seems to be different.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Experimentais/tratamento farmacológico , Compostos de Mostarda Nitrogenada/farmacologia , Animais , Antineoplásicos/metabolismo , Sítios de Ligação , Ratos , Relação Estrutura-Atividade
17.
Neoplasma ; 27(3): 271-8, 1980.
Artigo em Inglês | MEDLINE | ID: mdl-7453847

RESUMO

Quantitative structure--activity relationships have been fomulated for 27 aromatic nitrogen mustards derived from benzoic acids (9 monosubstituted and 18 disubstituted derivatives). Their toxicity (LD50) and antitumor activity against Jensen sarcoma were correlated with hydrolysis rate (log k66) lipophilicity constants (pi) and steric parameters (MDT). The chemical reactivity of the nitrogen mustard moiety (expressed as log k66) seems to be of main importance in determining the biological properties of these derivatives. The favorable effect of ortho-substitution was pointed out. Generally these results are in good agreement with those obtained by HANSCH et al. [7] on a different series of nitrogen mustards.


Assuntos
Antineoplásicos/farmacologia , Compostos de Mostarda Nitrogenada/farmacologia , Animais , Antineoplásicos/toxicidade , Neoplasias Experimentais/tratamento farmacológico , Ratos , Relação Estrutura-Atividade
18.
Neoplasma ; 32(6): 695-707, 1985.
Artigo em Inglês | MEDLINE | ID: mdl-4088389

RESUMO

Quantitative structure-activity relationships (QSAR) were formulated for a series of 22 phenolic inhibitors of carcinogenesis, taking into account: a) the inhibition of forestomach tumor induction in benzo(a)pyrene fed mice, as biological parameter and b) minimal topological differences (MTD), lipophilicities, quantum mechanic indices (epsilon LE, epsilon HO, and delta E1) and Hammett constants, as structural and physicochemical ones. Significant multilinear regression equations were found for a set of 22 compounds, two 2,6-di-tert-butyl derivatives (4 and 22) diverting from the general correlations. The obtained correlations support the conclusion that the antioxidizing potential is not directly responsible (in a rate determining step) for the inhibitory properties of the investigated phenols.


Assuntos
Antioxidantes/farmacologia , Carcinógenos/antagonistas & inibidores , Neoplasias Experimentais/induzido quimicamente , Fenóis/farmacologia , Animais , Fenômenos Químicos , Físico-Química , Feminino , Lipídeos , Camundongos , Solubilidade , Relação Estrutura-Atividade
19.
Acta Histochem ; 66(2): 220-33, 1980.
Artigo em Alemão | MEDLINE | ID: mdl-6774581

RESUMO

In vivo effects of Wofatox and DFP has been studied by light and electron microscopic histochemical methods in the central nervous system, in cardiac and striated muscles of rats. Singleintraperitoneal injection of Wofatox and DFP LD50 resulted in complete inhibition of the histochemically detectable acetyIcholinesterase (AChE) activity in the central nervous system. Various striated muscles exhibit different degrees of sensitivity towards inhibitors, neither can the enzyme activity of some motor end plates be completely inhibited. In addition to AChE inhibition in striated muscles, organophosphorous compounds induce also subacute myopathic changes. In the case of a lethal intoxication, ultra-structural alterations suggesting myocardial lesion can be observed.


Assuntos
Acetilcolinesterase/metabolismo , Sistema Nervoso Central/efeitos dos fármacos , Isoflurofato/farmacologia , Músculos/efeitos dos fármacos , Compostos Organofosforados/farmacologia , Animais , Sistema Nervoso Central/enzimologia , Coração/efeitos dos fármacos , Músculos/enzimologia , Ratos
20.
Med Hypotheses ; 51(1): 1-3, 1998 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9881828

RESUMO

An attempt is made to assess the total number of the theoretically possible antigenic epitopes, the number of lymphocyte clones and the number of epitopes on cell surface antibody of a clone may be able to recognize. We suggest that the structures of recognizing antibody sites of a human are far from random and derived from a limited number of structures adapted to the recognition of pathogenic agents. The probability of recognition for a random epitope-like structure is likely to be very small. Discriminative power of BCR and TCR binding sites, together with T-helper control, should be sufficient for prevention of peripheral autoimmune response, but second-signal-type controls should not be neglected as supplementary mechanisms to prevent such response.


Assuntos
Tolerância Imunológica , Linfócitos/imunologia , Modelos Imunológicos , Anticorpos/imunologia , Reações Antígeno-Anticorpo , Antígenos/imunologia , Sítios de Ligação de Anticorpos/imunologia , Epitopos/imunologia , Humanos , Receptores de Antígenos de Linfócitos B/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Linfócitos T/imunologia
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