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1.
Niger J Clin Pract ; 26(4): 497-501, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37203116

RESUMO

Background: Postoperative paralytic ileus refers to the disruption of the normal coordinated propulsive motor activity of the gastrointestinal system following surgery. Surgery causes inflammation in the muscle walls of organs with an intestinal lumen that, in turn, leads to a decrease in intestinal motility. Aim: The aim of this study was to investigate the efficacy of gastrografin, neostigmine, and their combined administration in patients diagnosed with paralytic ileus in the postoperative period. Patients and Methods: One-hundred twelve patients were included from January 2017 and November 2019. The retrospective study is involving prolonged postoperative ileus cases following colorectal surgery. The effect of gastrografin, neostigmine, and gastrografin neostigmine combination was compared retrospectively in the treatment of prolonged ileus after surgery. Results: The study covered 112 patients. Gastrografin was administered to 63 patients; neostigmine was administered to 29, while 20 patients received the combination of the two. Data pertaining to the comparison of the two groups revealed that patients in the gastrografin group were discharged earlier than those in the neostigmine group. Further, patients in the combined group had earlier gas and/or stool discharge and were also discharged from the hospital earlier than those in the neostigmine group. Conclusion: Gastrografin and combined use of gastrografin and neostigmine are effective and viable methods for postoperative ileus cases. Gastrografin can safely be used in patients with anastomoses.


Assuntos
Íleus , Pseudo-Obstrução Intestinal , Humanos , Neostigmina/uso terapêutico , Estudos Retrospectivos , Diatrizoato de Meglumina , Íleus/tratamento farmacológico , Íleus/etiologia , Complicações Pós-Operatórias/tratamento farmacológico , Pseudo-Obstrução Intestinal/complicações
2.
Rev Med Liege ; 77(1): 56-62, 2022 Jan.
Artigo em Francês | MEDLINE | ID: mdl-35029342

RESUMO

Macrocephaly is a frequent reason for seeking advice in a pediatric neurology consultation. It is a non-specific neurological sign that can be isolated, be the sign of a serious acquired pathology or be part of a syndromic picture. Clinical history, physical examination and imaging are key elements of the diagnostic strategy. Signs of intracranial hypertension require an emergency work-up. Genetics, exome in particular, has enabled the characterization of various syndromes associating macrocephaly and neurodevelopmental delay. In this article, we propose an update of practices based on clinical signs.


La macrocéphalie est un motif fréquent de demande d'avis en consultation de neuropédiatrie. Il s'agit d'un signe somatique peu spécifique et pouvant être isolé, être le signe d'une pathologie acquise grave ou faire partie d'un tableau syndromique. L'anamnèse, l'examen clinique et l'imagerie sont des éléments clés de la stratégie diagnostique. La découverte de signes d'hypertension intracrânienne implique une mise au point en urgence. La génétique, notamment la réalisation de l'exome, a permis la caractérisation de différents syndromes associant la macrocéphalie et des troubles du neurodéveloppement. Compte tenu des évolutions technologiques, une mise à jour des pratiques, basée sur la clinique, est proposée dans cet article.


Assuntos
Megalencefalia , Criança , Humanos , Megalencefalia/diagnóstico
3.
Bratisl Lek Listy ; 122(7): 489-492, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34161116

RESUMO

OBJECTIVES: In this study, we aimed to demonstrate the relationship between he neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), neutrophil/monocyte rate (NMR) and mean platelet volume (MPV) in patients with BIRADS grades of benign breast lesions. BACKGROUND: In many recent studies, NLR, PLR, NMR and MPV change significantly in connection with chronic inflammation and are suggested for use as prognostic markers in some diseases. However, the relationship between the cancer probability of benign breast diseases and mentioned hematological parameters has not been investigated in any previous study. We used the BIRADS classification to evaluate the malignancy probability of the cases. METHODS: The hospital database of records of patients who were over 15 years of age and examined with bilateral ultrasonography between October 2019 and February 2020 were retrospectively scanned. RESULTS: In total, 168 patients were included in the study. The average NLR and NMR values were higher in the BIRADS 2 group. There was no significant difference between the average PLR and MPV values of BIRADS groups. CONCLUSIONS: Although some results seem to be statistically significant, there was no significant relationship between the hematological parameters we examined and the BIRADS grades of benign breast lesions (Tab. 2, Ref. 18).


Assuntos
Volume Plaquetário Médio , Neutrófilos , Humanos , Linfócitos , Masculino , Monócitos , Estudos Retrospectivos
4.
Rev Med Liege ; 75(10): 686-691, 2020 Oct.
Artigo em Francês | MEDLINE | ID: mdl-33030847

RESUMO

Global developmental delay (GDD) and intellectual development disorder (IDD) are common but heterogeneous pediatric conditions. Guided by a rigorous clinical and anamnestic examination, the diagnostic approach is a dynamic process which is not limited to the intelligence quotient measurement. A large panel of paraclinical tests allows etiological exploration; this generally includes biological, genetic, metabolic and iconographic examinations. To maximize therapeutic efficiency and standardize practices, this document provides a guideline for the management of pediatric GDD/IDD.


Le retard global du développement (RGD) et le trouble du développement intellectuel (TDI) forment un groupe hétérogène de pathologies pédiatriques relativement fréquentes. Orientée par un examen clinique et anamnestique rigoureux, la démarche diagnostique est un processus dynamique qui ne se limite pas au quotient intellectuel. Son exploration étiologique est menée à travers un large panel d'examens paracliniques qui comprend généralement des examens biologiques, génétiques, métaboliques et iconographiques. Afin d'optimiser le rendement thérapeutique et d'homogénéiser les pratiques, ce document propose un cadre pour la mise au point des RGD/TDI en pédiatrie.


Assuntos
Deficiências do Desenvolvimento , Deficiência Intelectual , Criança , Cognição , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/etiologia , Família , Humanos , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/etiologia
5.
Eur J Cancer Care (Engl) ; 25(1): 112-21, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25040559

RESUMO

This study was performed to evaluate psychiatric symptoms and resilience levels of the hematopoietic stem cell transplant patients and their relatives. The study enrolled 51 patients and 45 relatives undergoing bone marrow transplantation. Data were collected using Personal Information Form, Brief Symptom Inventory and Resilience Scale for Adults. Psychiatric symptoms of both patients and their relatives were negatively associated with resilience levels. Patients and their relatives with a higher degree of resilience showed a lower degree of psychiatric symptoms. The study results demonstrate that haematopoietic stem cell transplantation is a process that affects patients as well as their families. We suggest that patients and their family members be evaluated for psychiatric symptoms by nurses during this process and resilience level of patients be increased by helping them improve their coping and problem-solving skills for adaptation throughout the process.


Assuntos
Adaptação Psicológica , Família/psicologia , Transplante de Células-Tronco Hematopoéticas/psicologia , Transtornos Mentais/etiologia , Resiliência Psicológica , Adolescente , Adulto , Idoso , Ansiedade/psicologia , Feminino , Humanos , Masculino , Transtornos Mentais/psicologia , Pessoa de Meia-Idade , Resolução de Problemas , Escalas de Graduação Psiquiátrica , Estresse Psicológico/etiologia , Estresse Psicológico/prevenção & controle , Estresse Psicológico/psicologia , Adulto Jovem
6.
Spinal Cord ; 53(8): 625-9, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25708664

RESUMO

STUDY DESIGN: Cross-sectional study. OBJECTIVES: Our aim was to compare the effects of repeated cystometric measurements in spinal cord injury (SCI) patients with neurogenic detrusor overactivity (NDO) who use indwelling catheters (IDC) or intermittent catheterization (IC). SETTING: Turkey. METHODS: A total of 20 SCI patients with NDO, 9 patients on IC and 11 on IDC for at least two consecutive months were included. After emptying the bladder, first involuntary detrusor contraction volume (1stIDCV), cystometric bladder capacity (CC), bladder compliance and maximum detrusor pressure (MPdet) were assessed by filling it with sterile physiological saline at room temperature at a continuous rate of 30 ml min(-1). The bladder was re-emptied after the process and a second filling cystometry was performed in the same way. RESULTS: When all study population were taken into account, 1stIDCV and CC measures were significantly increased in the second cystometry compared with the first cystometry (P=0.001 and P=0.022, respectively), whereas there was no statistically significant difference on bladder compliance and MPdet measures between the first and the repeated cystometry. There was no statistically significant difference on 1stIDCV, CC and bladder compliance measures between the first and the repeated cystometries for IC group, whereas there was statistically significant increase on these measures in the IDC group (P=0.003, P=0.008 and P=0.022, respectively). In addition there was no statistically significant difference on MP(det) measures between the first and the repeated cystometries for both the urine drainage methods. When IC and IDC groups were compared according to mean values of differences in 1stIDCV, CC and bladder compliance measures between the two cystometries, the IDC group had a statistically significant increase in all parameters when compared with the IC group in the second cystometry performed (P=0.001, P=0.003 and P=0.048, respectively). CONCLUSION: Repeated cystometric measurements in SCI patients with NDO lead to an increase in 1stIDCV and CC. However, when the type of urine drainage method is taken into account, although repeated filling cystometry leads to an increase in 1stIDCV, MCC and bladder compliance in patients with IDC, it does not cause a difference in patients on IC.


Assuntos
Traumatismos da Medula Espinal/complicações , Bexiga Urinária Hiperativa/etiologia , Bexiga Urinária Hiperativa/terapia , Cateterismo Urinário/métodos , Adulto , Idoso , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
7.
Allergy ; 68(5): 593-603, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23480796

RESUMO

BACKGROUND: The fine balance of immunoglobulins (Ig) E, IgG1, IgG4 and IgA in healthy production is maintained by the interaction of B cells with adaptive and innate immune response. The regulation of toll-like receptors (TLRs)-driven innate and adaptive immune effector B-cell response and the role of mammalian telomeric TTAGGG repeat elements represent an important research area. METHODS: Human PBMC and purified naive and memory B cells were stimulated with specific ligands for TLR2, TLR3, TLR4, TLR5, TLR7, TLR8 and TLR9 in the presence or absence of telomeric oligonucleotides. B-cell proliferation, differentiation and antibody production were determined. RESULTS: TLR9 ligand directly activates naive and memory B cells, whereas TLR7 can stimulate them in the presence of plasmacytoid dendritic cells. Human B cells proliferate and turn into antibody-secreting cells in response to TLR3, TLR7 and TLR9, but not to TLR2, TLR4, TLR5 and TLR8 ligands. Stimulation of B cells with intracellular TLR3, TLR7 and TLR9 induced an activation cascade leading to memory B-cell generation and particularly IgG1, but also IgA, IgG4 and very low levels of IgE production. Mammalian telomeric oligodeoxynucleotide (ODN) significantly inhibited all features of TLR ligand-induced events in B cells including B-cell proliferation, IgE, IgG1, IgG4, IgA production, class switch recombination, plasma cell differentiation induced by TLR3, TLR7 and TLR9 ligands. CONCLUSION: B cells require specific TLR stimulation, T-cell and plasmacytoid dendritic cell help for distinct activation and Ig production profiles. Host-derived telomeric ODN suppress B-cell activation and antibody production demonstrating a natural mechanism for the control of overexuberant B-cell activation, antibody production and generation of memory.


Assuntos
Linfócitos B/imunologia , Imunoglobulina A/biossíntese , Imunoglobulina E/biossíntese , Imunoglobulina G/biossíntese , Ativação Linfocitária/efeitos dos fármacos , Oligonucleotídeos/farmacologia , Telômero/química , Animais , Linfócitos B/citologia , Linfócitos B/metabolismo , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/imunologia , Humanos , Switching de Imunoglobulina/efeitos dos fármacos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/imunologia , Ligantes , Transdução de Sinais/efeitos dos fármacos , Receptor 3 Toll-Like/imunologia , Receptor 7 Toll-Like/imunologia , Receptor Toll-Like 9/imunologia , Recombinação V(D)J/efeitos dos fármacos
9.
J Exp Med ; 178(5): 1655-63, 1993 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-8228812

RESUMO

An increased ratio of T helper type 2 (Th2)- vs Th1-like cells contributes to the immune dysregulation in allergic disease situations and in many chronic infections, including AIDS. Th2-type immune responses are characterized by Th cells that produce increased levels of interleukin-4 (IL-4) and decreased levels of interferon gamma (IFN-gamma). The induction of either a Th1- or a Th2-like phenotype may be critically controlled by the antigen-presenting cells and their cytokines, e.g., IFN-alpha. In this study we have determined the frequencies of potential IL-4- and/or IFN-gamma-producing T cells in the peripheral blood of randomly selected healthy individuals, and analyzed whether IFN-alpha controls IL-4 and/or IFN-gamma production. Purified CD4+ or CD8+ T cells were stimulated for 24 h via the T cell receptor/CD3 complex in the presence or absence of IFN-alpha, and single IL-4- and IFN-gamma-secreting cells were detected in enzyme-linked immunospot assays. In the absence of IFN-alpha, CD4 cells produced IFN-gamma at frequencies of 1:50-300, and produced IL-4 at frequencies of 1:110-<1:100,000. Addition of IFN-alpha during the activation of CD4 cells increased the levels of IFN-gamma mRNA. As a consequence, the numbers of IFN-gamma-producing CD4 cells and the amounts of secreted IFN-gamma increased 10-fold. In contrast, IFN-alpha did not increase the frequency of IL-4-secreting CD4 cells. In the absence of IFN-alpha, addition of exogenous IL-4 to cultures of CD4 cells suppressed IFN-gamma secretion by 70%. However, in the presence of IFN-alpha, IL-4 did not display any suppressive effect. Compared with CD4 cells, CD8 cells produced IFN-gamma more frequently (1:5-10) but IL-4 less frequently (1:5,300 to < 1:100,000). IFN-alpha did not display any effect on the frequency of either IFN-gamma or IL-4 production by CD8 cells. Taken together the results indicate that IFN-alpha increases the frequency of IFN-gamma-secreting CD4 Th cells and antagonizes the suppressive effect of IL-4 on IFN-gamma production. As a consequence, IFN-alpha may favor the induction and maintenance of Th1-like cells and thereby counteract Th2-driven allergic immune responses.


Assuntos
Antígenos CD4/imunologia , Interferon Tipo I/farmacologia , Interferon gama/biossíntese , Subpopulações de Linfócitos T/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Síndrome da Imunodeficiência Adquirida/imunologia , Separação Celular/métodos , Relação Dose-Resposta a Droga , Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-4/biossíntese , Cinética , RNA Mensageiro/biossíntese , Proteínas Recombinantes , Subpopulações de Linfócitos T/efeitos dos fármacos , Linfócitos T Auxiliares-Indutores/efeitos dos fármacos
10.
J Exp Med ; 135(6): 1228-46, 1972 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-4112562

RESUMO

L-Tyrosine azobenzene-p-arsonate (RAT) induced cellular immunity without antibody production in guinea pigs. Bifunctional antigens were prepared consisting of one RAT carrier moiety linked either directly to a dinitrophenyl (DNP) haptenic determinant or through one or more 6-amino-caproyl (SAC) spacers. Each SAC unit has an extended span of 8 A. Guinea pigs immunized with these conjugates developed cellular immunity directed against the RAT determinant and antibody specific for the DNP determinant. The anti-DNP response was the same with one or three SAC spacers, but was significantly weaker when the two determinants were joined without a spacer. Animals immunized with either DNP-SAC-TYR or DNP-TYR developed neither cellular nor humoral immunity. Prior immunization with RAT potentiated the secondary anti-hapten response to DNP-SAC-RAT. Modification of RAT at either the arsonate or tyrosine positions showed that other charged groups (sulfonate and trimethylammonium) could substitute for arsonate without loss of immunogenicity. Removal of either the amino or carboxyl group from the side chain of tyrosine did not abolish immunogenicity, but immunogenicity was lost upon removal of both. Immunization with symmetrical bifunctional RAT-(SAC)(n)-RAT and cyclo-(L-RAT-D-RAT) antigens led to cellular immunity but no anti-arsonate antibody, suggesting a barrier to "self-help." These compounds were also ineffective in inducing a secondary anti-arsonate response in animals primed with arsonate-BSA conjugates and RAT.


Assuntos
Epitopos , Imunidade Celular , Animais , Formação de Anticorpos , Arsenicais , Compostos Azo , Dinitrofenóis , Cobaias , Haptenos/antagonistas & inibidores , Hipersensibilidade Tardia , Imunização , Imunoquímica , Nitrobenzenos , Relação Estrutura-Atividade , Tirosina
11.
J Exp Med ; 136(6): 1478-83, 1972 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-4118413

RESUMO

L-Tyrosine-p-azobenzenearsonate (RAT) induces cellular immunity without humoral antibody in guinea pigs. Asymmetric bifunctional antigens composed of one RAT moiety and one dinitrophenyl (DNP) group separated by flexible spacers induce anti-RAT cellular immunity and an anti-DNP humoral response. Symmetrical bifunctional antigens of similar design but comprised of two RAT determinants induce cellular immunity without demonstrable anti-RAT antibody. However, when the flexible spacer is replaced by a rigid decaproline chain, humoral anti-RAT responses are provoked. Since RAT contains both electropositive (azo) and electronegative (arsonate) centers, the failure of bifunctional RAT compounds with flexible spacers to induce humoral immunity might be ascribed either to intramolecular stacking, which compromises their bifunctional character, or to interaction of both determinants with receptors on the same cell surface, which would fail to satisfy the requirement for cooperation. In order to distinguish between these alternatives, symmetrical bifunctional antigens composed of two L-tyrosine-p-azophenyltrimethylammonium (TAT) determinants separated by flexible or rigid spacers were synthesized. TAT is immunogenic and does not cross-react with RAT. Furthermore, it contains only electropositive centers and consequently bifunctional molecules do not undergo intramolecular stacking. Immunization with either flexibly or rigidly spaced bifunctional TAT antigens raised anti-TAT antibody. These results conclusively demonstrate that "self-help," cooperation between bone marrow-derived and thymus-derived lymphocytes of identical or similar specificity, can occur, provided the determinants on the antigen are prevented from associating with each other.


Assuntos
Compostos Azo/farmacologia , Sítios de Ligação de Anticorpos , Epitopos , Imunidade Celular , Memória Imunológica , Animais , Formação de Anticorpos , Arsenicais/farmacologia , Cobaias , Haptenos , Hipersensibilidade Tardia , Testes de Precipitina , Compostos de Amônio Quaternário/farmacologia , Testes Cutâneos , Tirosina , p-Azobenzenoarsonato
12.
J Exp Med ; 136(2): 387-91, 1972 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-5043418

RESUMO

The low molecular weight compound L-tyrosine-azobenzenearsonate (RAT) induces a cellular immune response in guinea pigs. The contribution of the side chain of tyrosine to the immunogenicity of RAT and the structural requirements at that position for immunogenicity were assessed by synthesizing a series of analogs of RAT containing modifications in the side chain of tyrosine and employing them as immunogens. Removal of either the carboxyl or amino group did not markedly affect immunogenicity, measured by the induction of delayed cutaneous sensitivity, whereas deletion of both completely abolished it. However, a charged group was not required since side chains containing a polar hydroxyl group could substitute for chains bearing an amino or carboxyl group. The size of the side chain exerted a pronounced influence; the charged or polar substituent had to be extended from the phenolic ring by at least two carbon atoms in order to confer immunogenicity.


Assuntos
Formação de Anticorpos , Antígenos , Arsenicais , Compostos Azo , Haptenos , Tirosina , Animais , Cobaias , Hipersensibilidade Tardia , Relação Estrutura-Atividade
13.
J Exp Med ; 169(2): 519-33, 1989 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-2492056

RESUMO

We have found that syngeneic Ab2s in the antiarsonate system are serologically and structurally similar to one another. In contrast, the allogeneic Ab2 response is heterogeneous and derives from a large number of unrelated germline gene segments. The Ab2 response of the BALB/c strain to polyclonal A/J Ars A molecules can probably best be compared with a response to a foreign protein and might have been predicted in a strain that completely lacks the H chain V region gene from which the Ab1 derives. Partial variable region sequences of Ab2s from three other systems in addition to previously reported Ab2 structures indicates that this difference in allogeneic vs. syngeneic Ab2s may be a general phenomena. These data support Jerne's hypothesis of complementary V region genes existing in the germline. However, there is good evidence that these antiidiotypic antibodies are not derived directly from the germline, as somatic processes most likely play an important role in their generation. The D segments of Ab2s in the arsonate system as well as in other systems, are novel in structure and cannot easily be explained by previously described germline D segments. D-D fusion may play a role in the generation of the third hypervariable region in these antibodies.


Assuntos
Anticorpos Anti-Idiotípicos/genética , Rearranjo Gênico do Linfócito B , Genes de Imunoglobulinas , Idiótipos de Imunoglobulinas/imunologia , Sequência de Aminoácidos , Animais , Anticorpos Monoclonais/imunologia , Sequência de Bases , Cadeias Pesadas de Imunoglobulinas/genética , Região Variável de Imunoglobulina/genética , Cadeias kappa de Imunoglobulina/genética , Camundongos , Dados de Sequência Molecular , p-Azobenzenoarsonato/imunologia
14.
Acta Paediatr ; 99(7): 993-6, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20219048

RESUMO

AIM: To investigate the effect of anaesthetic agents on transcutaneous bilirubin levels during the first 24 h in neonates delivered by caesarean section. METHODS: A total of 168 neonates delivered by caesarean section, during which sevoflurane was used for general anaesthesia (group A), bupivacaine for spinal anaesthesia (group B), levobupivacaine for epidural anaesthesia (group C) and 155 neonates delivered vaginally were included in the study. Transcutaneous bilirubin levels (TBLs) of infants were measured during the first 24 h and compared with each other. RESULTS: The TBLs in neonates delivered vaginally were higher than those delivered by caesarean section, but the difference was not significant. TBLs were higher in groups A and C than in group B (p = 0.034, p = 0.011 respectively). TBLs were higher in group C than in group A, but the difference was not significant (p > 0.05). When the groups were compared with vaginal delivery group, TBLs in groups A and C were found higher (p = 0.03, p = 0.022 respectively). CONCLUSION: The route of delivery had no effect on TBL. While bupivacaine was found to have no effect on neonatal bilirubin levels, levobupivacaine increased neonatal biluribin levels, but further studies are needed for definite results.


Assuntos
Anestesia Obstétrica/efeitos adversos , Anestésicos/efeitos adversos , Cesárea , Hiperbilirrubinemia Neonatal/induzido quimicamente , Adulto , Anestesia por Condução , Anestesia Geral , Bilirrubina/sangue , Bupivacaína/efeitos adversos , Bupivacaína/análogos & derivados , Feminino , Humanos , Recém-Nascido , Levobupivacaína , Masculino , Éteres Metílicos/efeitos adversos , Gravidez , Sevoflurano
15.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31734189

RESUMO

Tumor thrombus is an intravascular malign tumor extension that may occur in various types of cancer. Hepatocellular carcinomas (HCC) are common causes of malign thrombus. The presence of a malign thrombus due to HCC has a dismal prognosis, which affects treatment choices. We present three cases of tumor thrombi due to advanced HCC detected by 18F-FDG PET/CT.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/secundário , Fluordesoxiglucose F18 , Neoplasias Hepáticas/patologia , Células Neoplásicas Circulantes , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos
16.
J Clin Invest ; 98(7): 1676-83, 1996 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-8833918

RESUMO

Bee venom phospholipase A2 (PLA) is the major allergen in bee sting allergy. It displays three peptide and a glycopeptide T cell epitopes, which are recognized by both allergic and non-allergic bee venom sensitized subjects. In this study PLA- and PLA epitope-specific T cell and cytokine responses in PBMC of bee sting allergic patients were investigated before and after 2 mo of rush immunotherapy with whole bee venom. After successful immunotherapy, PLA and T cell epitope peptide-specific T cell proliferation was suppressed. In addition the PLA- and peptide-induced secretion of type 2 (IL-4, IL-5, and IL-13), as well as type 1 (IL-2 and IFN-gamma) cytokines were abolished, whereas tetanus toxoid-induced cytokine production and proliferation remained unchanged. By culturing PBMC with Ag in the presence of IL-2 or IL-15 the specifically tolerized T cell response could be restored with respect to specific proliferation and secretion of the type 1 T cell cytokines, IL-2 and IFN-gamma. In contrast, IL-4, IL-5, and IL-13 remained suppressed. Treatment of tolerized T cells with IL-4 only partially restored proliferation and induced formation of distinct type 2 cytokine pattern. In spite of the allergen-specific tolerance in T cells, in vitro produced anti-PLA IgE and IgG4 Ab and their corresponding serum levels slightly increased during immunotherapy, while the PLA-specific IgE/IgG4 ratio changed in favor of IgG4. These findings indicate that bee venom immunotherapy induces a state of peripheral tolerance in allergen-specific T cells, but not in specific B cells. The state of T cell tolerance and cytokine pattern can be in vitro modulated by the cytokines IL-2, IL-4, and IL-15, suggesting the importance of microenvironmental cytokines leading to success or failure in immunotherapy.


Assuntos
Alérgenos/uso terapêutico , Venenos de Abelha/uso terapêutico , Anergia Clonal/imunologia , Linfócitos/imunologia , Fosfolipases A/imunologia , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Epitopos , Humanos , Imunoglobulina E/imunologia , Imunoglobulina G/imunologia , Interferon gama/biossíntese , Interleucinas/biossíntese , Interleucinas/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Pessoa de Meia-Idade , Fosfolipases A2 , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia
17.
Leuk Lymphoma ; 47(7): 1369-78, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16923571

RESUMO

Heat shock protein 90 (HSP90) is required for structural folding and maintenance of conformational integrity of various proteins, including several associated with cellular signaling. Recent studies utilizing 17-allylamino-17-demethoxygeldanamycin (17-AAG), an inhibitor of HSP90, demonstrated an antitumor effect in solid tumors. To test whether HSP90 could be targeted in multiple myeloma (MM) patients, we first investigated expression of HSP90 by immunofluorescence and flow cytometric analysis in a myeloma cell line (U266) and primary myeloma cells. Following demonstration of HSP90 expression in myeloma cells, archival samples of 32 MM patients were analysed by immunoperoxidase staining. Myeloma cells in all patients showed strong cytoplasmic expression of HSP90 in all samples and 55% also demonstrated concurrent nuclear immunopositivity. Treatment of U266 and primary MM cells with 17AAG resulted in significantly increased apoptosis compared to untreated control cells. Analysis of anti-apoptotic BCL2 family proteins and akt in MM cells incubated with 17-AAG revealed down-regulation of BCL-2, BCL-XL, MCL-1 and akt. Furthermore, although a low concentration of bortezomib resulted in no cell death, a combination of 17AAG and bortezomib treatment revealed a synergistic apoptotic effect on the U266 cell line. These data suggest that targeted inhibition of HSP90 may prove to be a valid and innovative strategy for the development of future therapeutic options for MM patients.


Assuntos
Apoptose , Benzoquinonas/farmacologia , Inibidores Enzimáticos/farmacologia , Regulação Neoplásica da Expressão Gênica , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Proteínas de Choque Térmico HSP90/biossíntese , Lactamas Macrocíclicas/farmacologia , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular , Citometria de Fluxo , Humanos , Microscopia de Fluorescência , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
18.
Leukemia ; 30(5): 1155-65, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26847029

RESUMO

BCOR is a component of a variant Polycomb group repressive complex 1 (PRC1). Recently, we and others reported recurrent somatic BCOR loss-of-function mutations in myelodysplastic syndrome and acute myelogenous leukemia (AML). However, the role of BCOR in normal hematopoiesis is largely unknown. Here, we explored the function of BCOR in myeloid cells using myeloid murine models with Bcor conditional loss-of-function or overexpression alleles. Bcor mutant bone marrow cells showed significantly higher proliferation and differentiation rates with upregulated expression of Hox genes. Mutation of Bcor reduced protein levels of RING1B, an H2A ubiquitin ligase subunit of PRC1 family complexes and reduced H2AK119ub upstream of upregulated HoxA genes. Global RNA expression profiling in murine cells and AML patient samples with BCOR loss-of-function mutation suggested that loss of BCOR expression is associated with enhanced cell proliferation and myeloid differentiation. Our results strongly suggest that BCOR plays an indispensable role in hematopoiesis by inhibiting myeloid cell proliferation and differentiation and offer a mechanistic explanation for how BCOR regulates gene expression such as Hox genes.


Assuntos
Diferenciação Celular , Proliferação de Células , Células Progenitoras Mieloides/citologia , Proteínas Repressoras/fisiologia , Animais , Regulação da Expressão Gênica , Genes Homeobox/genética , Hematopoese , Humanos , Leucemia Mieloide Aguda/patologia , Camundongos , Mutagênese Sítio-Dirigida , Complexo Repressor Polycomb 1/fisiologia , Proteínas Repressoras/genética
19.
Cell Death Differ ; 9(1): 40-52, 2002 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11803373

RESUMO

The induction of apoptosis in human keratinocytes by UV radiation involves caspase-mediated cleavage and activation of protein kinase C delta (PKCdelta). Here we examined the role of PKC activation in caspase activation and disruption of mitochondria function by UV radiation. Inhibition of PKC partially blocked UV radiation-induced cleavage of PKCdelta, pro-caspase-3, and pro-caspase-8, and the activation of these caspases. PKC inhibition also blocked the UV-induced loss of mitochondria membrane potential, but did not block the release of cytochrome c from mitochondria. Expression of the active catalytic domain of PKCdelta was sufficient to induce apoptosis and disrupt mitochondrial membrane potential, however a kinase inactive PKCdelta catalytic domain did not. Furthermore, the PKCdelta catalytic fragment generated following UV radiation localized to the mitochondria fraction, as did ectopically expressed PKCdelta catalytic domain. These results identify a functional role for PKC activation in potentiating caspase activation and disrupting mitochondrial function during UV-induced apoptosis.


Assuntos
Apoptose , Caspases/metabolismo , Mitocôndrias/efeitos da radiação , Proteína Quinase C/metabolismo , Raios Ultravioleta , Apoptose/fisiologia , Linhagem Celular , Ativação Enzimática , Humanos , Isoenzimas/metabolismo , Queratinócitos/metabolismo , Queratinócitos/efeitos da radiação , Potenciais da Membrana/efeitos da radiação , Mitocôndrias/fisiologia , Proteína Quinase C-delta
20.
Acta Vet Hung ; 53(2): 257-64, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15959984

RESUMO

A modified surgical technique has been developed for repairing third-degree perineal lacerations in mares. Complications of the currently used methods include rectovaginal fistula formation, urine pooling, complete dehiscence of the repair, constipation, tenesmus and difficulty of performance in the practice. The modified method is simpler and more practical. This method was performed on eight Thoroughbred mares with third-degree perineal lacerations after delivery. The rectovestibular septum was reconstructed by three lines of sutures in a transverse direction in relation to the longitudinal axis of the rectum. In one of the eight cases pneumorectum was observed after using the new method. The conception rate obtained after using the new surgical technique was 62.5%. Pregnant mares delivered normally without any new lacerations at the subsequent parturition. It can be concluded that this new surgical technique can be used successfully for repairing third-degree perineal lacerations in mares.


Assuntos
Distocia/veterinária , Cavalos/lesões , Períneo/lesões , Técnicas de Sutura/veterinária , Animais , Feminino , Cavalos/cirurgia , Períneo/cirurgia , Gravidez
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