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1.
Rinsho Ketsueki ; 61(4): 312-317, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32378572

RESUMO

We present the case of a 39-year-old man with a primary diagnosis of mixed phenotype acute leukemia, T/myeloid not otherwise specified (T/M-MPAL). After achieving a complete remission (CR), he underwent allogeneic hematopoietic stem cell transplantation (HSCT). Subsequent evaluation of the cerebrospinal fluid suggested central nervous system graft versus host disease (GVHD); hence, prednisolone therapy was initiated. After 118 days on prednisolone, a routine follow-up thoracic and abdominal computed tomography (CT) revealed extensive pneumatosis in the wall of the colon. We diagnosed his condition as pneumatosis cystoides intestinalis (PCI). The patient was treated conservatively with high concentration oxygen. A CT scan performed 1 week later revealed that the pneumatosis had fully resolved; no relapse has been observed. Various etiologies of PCI have been reported previously. However, there are very few reports of PCI presenting in association with hematologic neoplasms or in response to allogeneic HSCT in adult patients.

2.
Clin Nucl Med ; 45(2): e88-e91, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31652159

RESUMO

F-FDG PET/CT for a 74-year-old man with elevated serum soluble interleukin 2 receptor showed multiple intense uptake in the liver, spleen, and bone. A surgical biopsy from 2 of liver tumors confirmed hepatosplenic αß T-cell lymphoma. One and a half months after biopsy, FDG PET scan was performed again for staging before starting chemotherapy, and it showed the complete disappearance of all of the lesions. The excisional biopsy could be a possible trigger of his spontaneous regression.

3.
Clin Nucl Med ; 44(11): 907-910, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31592826

RESUMO

A 70-year-old woman had spontaneous resolution of an embolism in her right middle cerebral artery (MCA) (day 1); another embolism occurred in her left MCA (day 3), which was promptly removed. On day 5, F-FDG PET/CT performed for staging mediastinal lymphoma showed marked FDG accumulation in the left MCA territory, whereas a defect was seen in the right insular region. Eventually, bilateral lesions developed irreversible infarction. Anaerobic metabolism and/or inflammation in acute-phase infarction were the supposed mechanism for the increased accumulation of FDG in her left MCA territory.


Assuntos
Fluordesoxiglucose F18/metabolismo , Infarto da Artéria Cerebral Média/metabolismo , Artéria Cerebral Média/metabolismo , Doença Aguda , Idoso , Feminino , Humanos , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Artéria Cerebral Média/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons
4.
Rinsho Ketsueki ; 60(8): 915-919, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31484889

RESUMO

A 83-year-old female patient was admitted to our hospital due to hematological manifestation of juvenile granulocytes and macrocytic anemia. Bone marrow (BM) examination revealed erythroid dysplasia and cytoplasmic blasts, and hence the patient was diagnosed with myelodysplastic syndrome with ring sideroblasts and with single lineage dysplasia (MDS-RS-SLD). Erythrocyte transfusion was performed as a supportive therapy, and there was a gradual increase in the number of blood cells. Therefore, BM re-examination was performed and it was confirmed that the number of megakaryocytes increased, so the patient's condition was determined as myelodysplastic/myeloproliferative neoplasms with ring sideroblasts and thrombocytosis (MDS/MPN with RS-T). Incidentally, gene mutation analysis showed CALR gene mutation. Thereafter, administration of hydroxycarbamide and anagrelide did not show adverse events and complications, and a good blood count control was obtained. Furthermore, it was also confirmed that an SF3B1 gene mutation is highly positive in MDS-RS. There was no report on CALR-mutant MDS/MPN in Japan, and it is a rare disease overseas.


Assuntos
Calreticulina/genética , Neoplasias Hematológicas/genética , Fosfoproteínas/genética , Fatores de Processamento de RNA/genética , Trombocitose , Idoso de 80 Anos ou mais , Feminino , Humanos , Japão , Mutação , Trombocitose/genética
5.
Cardiovasc Endocrinol Metab ; 7(2): 47-53, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31646280

RESUMO

Background: Glycemic variability (GV) induces coronary microcirculatory disturbance and myocardial damage in diabetic patients with acute myocardial infarction. However, in nondiabetic acute myocardial infarction patients, the relationship between GV and myocardial damage remains unclear. Patients and methods: We investigated GV with a continuous glucose monitoring system in nondiabetic ST-segment elevation myocardial infarction patients treated with emergent percutaneous coronary intervention. GV was expressed as the mean amplitude of glycemic excursions (MAGE). Myocardial damage was estimated by myocardial blush grade and ST-segment resolution (STRes). STRes was defined as complete (>70%), partial (30-70%), or none (<30%). Results: Consecutive patients (n=73) were enrolled and classified into a lower or higher MAGE group on the basis of the median MAGE. The higher MAGE group showed lower levels of myocardial blush grade (2.41±0.76 vs. 1.72±0.85, P=0.001) and STRes (complete: 56.8 vs. 33.3%, P=0.044; partial: 32.4 vs. 36.1%, P=0.741; none: 10.8 vs. 30.6%, P=0.037). Conclusion: GV was associated with myocardial damage after percutaneous coronary intervention in nondiabetic ST-segment elevation myocardial infarction patients.

6.
Intern Med ; 57(4): 511-515, 2018 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-29151508

RESUMO

A 77-year-old Japanese woman presented with asymptomatic abdominal lymphadenopathy. Soluble interleukin-2 receptor (sIL2R) and angiotensin-converting enzyme (ACE) levels were elevated, and a pathological examination of lymph-node biopsies revealed non-caseating granulomas, which was consistent with sarcoidosis. Fluorodeoxyglucose-positron emission tomography did not show a clear accumulation in the mediastinal lymph-nodes or heart. Five months later, she presented with acute progressive heart failure that was refractory to conventional treatment. Her sIL2R and ACE levels decreased spontaneously over time, without steroid treatment. Autopsy findings revealed non-caseating granulomas. Cardiac sarcoidosis presenting as acute, progressive, treatment-refractory heart failure is rare. Steroid therapy after the resolution of inflammation did not affect the clinical outcome.


Assuntos
Corticosteroides/uso terapêutico , Gastroenteropatias/fisiopatologia , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/fisiopatologia , Linfadenopatia/fisiopatologia , Sarcoidose/tratamento farmacológico , Sarcoidose/fisiopatologia , Idoso , Grupo com Ancestrais do Continente Asiático , Feminino , Gastroenteropatias/etiologia , Humanos , Linfonodos/fisiopatologia , Linfadenopatia/etiologia , Tomografia por Emissão de Pósitrons , Sarcoidose/etiologia , Resultado do Tratamento
7.
BMC Surg ; 16(1): 62, 2016 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-27624800

RESUMO

BACKGROUND: Primary amyloidosis of the breast is an unusual benign disease that mostly occurs in postmenopausal elderly women. Amyloidosis is the deposition of amorphous protein within tissues. Breast biopsy is necessary to make a definite diagnosis in order to avoid unnecessary surgical methods. Localized primary amyloidosis of the breast has a good prognosis. However, secondary amyloidosis is a systemic disease and has a poor prognosis. CASE PRESENTATION: We report the case of a 77-year-old female with primary amyloidosis of the breast. She noticed a lump in her left breast. Mammographic and ultrasonographic examinations indicated breast cancer. However, core needle biopsy showed amyloidosis, not cancer of the breast. For further examinations, the patient visited the outpatient clinics of the hematology, dermatology, and gastroenterology departments. She underwent bone marrow aspiration, computed tomography, cardiac ultrasonography, random skin biopsy, gastrofiberscopy, and colonofiberscopy. Plasma cell myeloma and systemic amyloidosis were ruled out, and localized breast amyloidosis was highly suspected. Lumpectomy was performed to make a definite diagnosis, and histological evaluations revealed that this patient had localized amyloidosis of the breast, and the deposited amyloid protein was of the amyloid light chain kappa type. CONCLUSIONS: Breast biopsy is necessary in order to avoid unnecessary surgical technique. A diagnosis should be achieved only through a histological evaluation. The main treatment of localized primary amyloidosis of the breast is surgical removal.


Assuntos
Amiloidose/diagnóstico , Neoplasias da Mama/diagnóstico , Mama/patologia , Idoso , Amiloidose/cirurgia , Biópsia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina , Mamografia , Mastectomia Segmentar
8.
Behav Pharmacol ; 26(7 Spec No): 681-90, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25932719

RESUMO

We have recently found that isolation-reared mice show hyperactivity during an encounter with an intruder. However, it is not known whether encounter-induced hyperactivity may model some aspects of psychiatric disorders. The present study examined the pharmacological profile of encounter-induced hyperactivity in isolation-reared mice. Encounter-induced hyperactivity was reduced by acute administration of various antidepressants including the tricyclic antidepressant desipramine (10 mg/kg), the selective serotonin (5-HT) reuptake inhibitors fluvoxamine (10 mg/kg) and paroxetine (10 mg/kg), the 5-HT/noradrenaline reuptake inhibitors venlafaxine (10 mg/kg) and duloxetine (10 mg/kg), the antipsychotic drug risperidone (0.01 mg/kg), the 5-HT2 antagonist ritanserin (1 mg/kg), and the glucocorticoid receptor antagonist RU-43044 (30 mg/kg). The α2 adrenoceptor agonist clonidine (0.03 mg/kg) and the 5-HT4 receptor agonist BIMU8 (30 mg/kg) also reduced encounter-induced hyperactivity. The effect of desipramine was blocked by the α2 adrenoceptor antagonist idazoxan (0.3 mg/kg). The effect of fluvoxamine was blocked by the 5-HT4 receptor antagonist GR125487 (3 mg/kg), but not the 5-HT1A receptor antagonist WAY100635 (1 mg/kg), the 5-HT3 receptor antagonist azasetron (3 mg/kg), or the 5-HT6 receptor antagonist SB399885 (3 mg/kg). The effect of venlafaxine was blocked by the simultaneous administration of idazoxan (0.3 mg/kg) and GR125487 (3 mg/kg), but not by either compound alone. These findings suggest that encounter-induced hyperactivity in isolation-reared mice is a robust model for testing the pharmacological profile of antidepressants, although the range of antidepressants tested is limited and some non-antidepressants are also effective. The present study also shows a key role of α2 and 5-HT4 receptors in the antidepressant effect in this model.


Assuntos
Atividade Motora/efeitos dos fármacos , Comportamento Social , Isolamento Social/psicologia , Animais , Animais não Endogâmicos , Benzimidazóis/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Desipramina/farmacologia , Cloridrato de Duloxetina/farmacologia , Fluvoxamina/farmacologia , Hidroxicorticosteroides/farmacologia , Idazoxano/farmacologia , Indóis/farmacologia , Masculino , Camundongos , Testes Neuropsicológicos , Oxazinas/farmacologia , Paroxetina/farmacologia , Piperazinas/farmacologia , Psicotrópicos/farmacologia , Piridinas/farmacologia , Risperidona/farmacologia , Ritanserina/farmacologia , Sulfonamidas/farmacologia , Cloridrato de Venlafaxina/farmacologia
9.
Int J Neuropsychopharmacol ; 18(11): pyv062, 2015 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-26025781

RESUMO

BACKGROUND: Reduced motivation is an important marker of psychiatric disorders, including depression. We describe the female encounter test, a novel method of evaluating reward-seeking behavior in mice. METHODS: The test apparatus consists of three open chambers, formed with partitions that allow the animal to move freely from one chamber to another. A test male mouse is habituated in the apparatus, and subsequently a female and male mouse are introduced into a wire-mesh box in the left and right chamber, respectively. The time the test male mouse spends in the female or male area is measured for 10 min. RESULTS: All six strains of mice tested showed a significant preference for female encounters. The preference was observed in 7-30-week-old mice. The preference was blocked by castration of the resident male test mouse, and was not affected by the phase of the menstrual cycle of the female intruder. The preference was impaired in mouse models of depression, including social isolation-reared, corticosterone-treated, and lipopolysaccharide-treated mice. The impairment was alleviated by fluvoxamine in isolation-reared and lipopolysaccharide-treated mice, and it was improved by the metabotropic glutamate 2/3 receptor antagonist LY341495 in corticosterone-treated mice. Encounter with a female, but not male, mouse increased c-Fos expression in the nucleus accumbens shell of test male mice. Furthermore, both the preference and encounter-induced increases in c-Fos expression were blocked by dopamine D1 and D2 receptor antagonists. CONCLUSIONS: These findings indicate that motivation in adult male mice can be easily evaluated by quantitating female encounters.


Assuntos
Camundongos/psicologia , Motivação , Testes Psicológicos , Recompensa , Comportamento Social , Aminoácidos/farmacologia , Animais , Antidepressivos de Segunda Geração/farmacologia , Castração , Comportamento de Escolha/efeitos dos fármacos , Comportamento de Escolha/fisiologia , Corticosterona , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/tratamento farmacológico , Transtorno Depressivo/fisiopatologia , Modelos Animais de Doenças , Desenho de Equipamento , Ciclo Estral , Antagonistas de Aminoácidos Excitatórios/farmacologia , Feminino , Fluvoxamina/farmacologia , Lipopolissacarídeos , Masculino , Camundongos/fisiologia , Núcleo Accumbens/efeitos dos fármacos , Núcleo Accumbens/metabolismo , Isolamento Social , Xantenos/farmacologia
10.
J Clin Immunol ; 34 Suppl 1: S35-45, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24793544

RESUMO

IgM exists as both a monomer on the surface of B cells and a pentamer secreted by plasma cells. Both pre-immune "natural" and antigen-induced "immune" IgM antibodies are important for protective immunity and for immune regulation of autoimmune processes by recognizing pathogens and self-antigens. Effector proteins interacting with the Fc portion of IgM, such as complement and complement receptors, have thus far been proposed but fail to fully account for the IgM-mediated protection and regulation. A major reason for this deficit in our understanding of IgM function seems to be lack of data on a long elusive Fc receptor for IgM (FcµR). We have recently identified a bona fide FcµR in both humans and mice. In this article we briefly review what we have learned so far about FcµR.


Assuntos
Linfócitos B/imunologia , Imunoglobulina M/imunologia , Receptores Fc/imunologia , Animais , Autoantígenos/imunologia , Humanos , Imunomodulação , Camundongos , Receptores Fc/isolamento & purificação
11.
Int J Neuropsychopharmacol ; 17(6): 883-93, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24405605

RESUMO

We recently showed that social encounter stimulation induces hyperactivity in mice reared in social isolation from early life and this is associated with the transient activation of prefrontal dopaminergic and serotonergic systems. In the present study, we examined the effect of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor antagonist 2, 3-dioxo-6-nitro-1, 2, 3, 4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide (NBQX) on encounter-induced behavioural and neurochemical changes to study the role of the receptor in abnormal behaviours in isolation-reared mice. The encounter to an intruder mouse induced hyperactivity with transient increases in prefrontal dopamine and serotonin levels in isolation-reared mice. NBQX attenuated the encounter-induced hyperactivity and the associated neurochemical changes in isolation-reared mice. In addition, NBQX reduced aggressive behaviour and cognitive impairment in isolation-reared mice, but did not affect depressive-like behaviour or spontaneous hyper-locomotion in these animals. The AMPA receptor agonist (S)-AMPA increased prefrontal dopamine and serotonin release, and this effect was higher in isolation-reared mice than in the group-reared mice, suggesting higher prefrontal AMPA receptor activity in isolation-reared mice. Furthermore, isolation rearing increased the expression of AMPA receptor subunits (GluR1, GluR2 and GluR3) and GluR1 Ser845 phosphorylation in the prefrontal cortex, but not in the hippocampus or nucleus accumbens. Taken together, these results suggest that an increase in AMPA receptor activity in the prefrontal cortex contributes to some, but not all, abnormal behaviours in isolation-reared mice.


Assuntos
Hipercinese/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Receptores de AMPA/metabolismo , Comportamento Social , Isolamento Social , Agressão/efeitos dos fármacos , Agressão/fisiologia , Agressão/psicologia , Animais , Animais não Endogâmicos , Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/fisiopatologia , Depressão/tratamento farmacológico , Depressão/etiologia , Depressão/fisiopatologia , Dopamina/metabolismo , Antagonistas de Aminoácidos Excitatórios/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/fisiopatologia , Hipercinese/psicologia , Masculino , Camundongos , Núcleo Accumbens/efeitos dos fármacos , Núcleo Accumbens/fisiopatologia , Córtex Pré-Frontal/efeitos dos fármacos , Quinoxalinas/farmacologia , Receptores de AMPA/agonistas , Receptores de AMPA/antagonistas & inibidores , Serotonina/metabolismo , Isolamento Social/psicologia
13.
J Exp Med ; 206(12): 2779-93, 2009 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-19858324

RESUMO

Although Fc receptors (FcRs) for switched immunoglobulin (Ig) isotypes have been extensively characterized, FcR for IgM (FcmuR) has defied identification. By retroviral expression and functional cloning, we have identified a complementary DNA (cDNA) encoding a bona fide FcmuR in human B-lineage cDNA libraries. FcmuR is defined as a transmembrane sialoglycoprotein of approximately 60 kD, which contains an extracellular Ig-like domain homologous to two other IgM-binding receptors (polymeric Ig receptor and Fcalpha/muR) but exhibits an exclusive Fcmu-binding specificity. The cytoplasmic tail of FcmuR contains conserved Ser and Tyr residues, but none of the Tyr residues match the immunoreceptor tyrosine-based activation, inhibitory, or switch motifs. Unlike other FcRs, the major cell types expressing FcmuR are adaptive immune cells, including B and T lymphocytes. After antigen-receptor ligation or phorbol myristate acetate stimulation, FcmuR expression was up-regulated on B cells but was down-modulated on T cells, suggesting differential regulation of FcmuR expression during B and T cell activation. Although this receptor was initially designated as Fas apoptotic inhibitory molecule 3, or TOSO, our results indicate that FcmuR per se has no inhibitory activity in Fas-mediated apoptosis and that such inhibition is only achieved when anti-Fas antibody of an IgM but not IgG isotype is used for inducing apoptosis.


Assuntos
Proteínas Reguladoras de Apoptose/imunologia , Linfócitos B/imunologia , Imunoglobulina M/imunologia , Proteínas de Membrana/imunologia , Receptores Fc/imunologia , Linfócitos T/imunologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Apoptose/imunologia , Proteínas Reguladoras de Apoptose/genética , Carcinógenos/farmacologia , Linhagem Celular , DNA Complementar/genética , DNA Complementar/imunologia , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/genética , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/genética , Ativação Linfocitária/imunologia , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos BALB C , Receptores Fc/genética , Acetato de Tetradecanoilforbol/farmacologia , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética , Regulação para Cima/imunologia , Receptor fas/genética , Receptor fas/imunologia
14.
J Immunol ; 181(6): 4229-39, 2008 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-18768880

RESUMO

Paired Ig-like receptors of activating (PIR-A) and inhibitory (PIR-B) isoforms are expressed by many hematopoietic cells, including B lymphocytes and myeloid cells. To determine the functional roles of PIR-A and PIR-B in primary bacterial infection, PIR-B-deficient (PIR-B(-/-)) and wild-type (WT) control mice were injected i.v. with an attenuated strain of Salmonella enterica Typhimurium (WB335). PIR-B(-/-) mice were found to be more susceptible to Salmonella infection than WT mice, as evidenced by high mortality rate, high bacterial loads in the liver and spleen, and a failure to clear bacteria from the circulation. Although blood levels of major cytokines and Salmonella-specific Abs were mostly comparable in the two groups of mice, distinct patterns of inflammatory lesions were found in their livers at 7-14 days postinfection: diffuse spreading along the sinusoids in PIR-B(-/-) mice vs nodular restricted localization in WT mice. PIR-B(-/-) mice have more inflammatory cells in the liver but fewer B cells and CD8(+) T cells in the spleen than WT mice at 14 days postinfection. PIR-B(-/-) bone marrow-derived macrophages (BMMphi) failed to control intracellular replication of Salmonella in vitro, in part due to inefficient phagosomal oxidant production, when compared with WT BMMphi. PIR-B(-/-) BMMphi also produced more nitrite and TNF-alpha upon exposure to Salmonella than WT BMMphi did. These findings suggest that the disruption of PIR-A and PIR-B balance affects their regulatory roles in host defense to bacterial infection.


Assuntos
Predisposição Genética para Doença/genética , Receptores Imunológicos/deficiência , Receptores Imunológicos/genética , Salmonelose Animal/genética , Salmonelose Animal/imunologia , Animais , Anticorpos Antibacterianos/biossíntese , Anticorpos Antibacterianos/sangue , Citocinas/biossíntese , Citocinas/sangue , Feminino , Mediadores da Inflamação/fisiologia , Fígado/imunologia , Fígado/microbiologia , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Isoformas de Proteínas/deficiência , Isoformas de Proteínas/genética , Isoformas de Proteínas/fisiologia , Receptores Imunológicos/fisiologia , Salmonelose Animal/microbiologia , Salmonelose Animal/patologia , Salmonella typhimurium/imunologia , Baço/imunologia , Baço/microbiologia , Baço/patologia
15.
Gan To Kagaku Ryoho ; 32(6): 867-71, 2005 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-15984534

RESUMO

A 46-year-old man was admitted to our hospital with swelling of a neck lymph node in June, 2002, and was diagnosed with adult T-cell leukemia/lymphoma (ATLL). As ATLL cells were detected in the peripheral blood after two courses of multi-agent chemotherapy (LSG 15), the treatment was changed to biweekly CHOP therapy. After two courses, hematological remission was achieved. Allogeneic bone marrow transplant (allo-BMT) from HTLV- negative and HLA-matched sibling donor was performed (conditioned with cyclophosphamide 60 mg/kg x 2 and total body irradiation 12 Gy). Cyclosporine A (CsA) and short-term methotrexate (MTX) were used for graft-versus-host disease prevention. Though the HTLV- provirus DNA (Southern blot) disappeared, HTLV-I provirus DNA (real-time PCR) T-cell receptor ygammachain gene rearrangement DNA (Southern blot) were detected in bone marrow after allo-BMT. MRD disappeared after the withdrawal of CsA. After the allo-BMT transplant, a graft-versus-ATLL (GVATLL) effect may be induced by abrupt discontinuation of immunosuppression.


Assuntos
Transplante de Medula Óssea , Efeito Enxerto vs Leucemia , Imunossupressão , Leucemia-Linfoma de Células T do Adulto/patologia , Leucemia-Linfoma de Células T do Adulto/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/administração & dosagem , Ciclosporina/administração & dosagem , DNA Viral/análise , Doxorrubicina/administração & dosagem , Vírus Linfotrópico T Tipo 1 Humano/genética , Humanos , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Neoplasia Residual , Prednisona/administração & dosagem , Indução de Remissão , Vincristina/administração & dosagem
16.
Int J Hematol ; 81(3): 220-7, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15814333

RESUMO

We evaluated the roles of nitric oxide (NO) derived from endothelial cells in neutrophil transendothelial migration (TEM). Pretreatment of human umbilical vein endothelial cells (HUVECs) with NG-nitro-L-arginine methyl ester hydrochloride (L-NAME) or NG-monomethyl L-arginine (L-NMMA), which are inhibitors of NO synthases, enhanced neutrophil TEM. Similar augmentation of TEM was observed in the presence of an NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy PTIO). Neutrophil TEM across L-NAME- or L-NMMA-treated HUVECs was inhibited by continuous NO supply by NO donors. These findings support the suggestion that continuous production of NO by endothelial cells suppresses neutrophil TEM. Flow cytometric analyses revealed that NO accumulates in neutrophils co-cultured with NO-producing HUVECs. A decreased amount of NO was detected in neutrophils co-cultured with L-NAME-treated HUVECs compared with neutrophils co-cultured with untreated HUVECs. Soluble guanylyl cyclase (sGC) is known as one of the most important targets of NO in neutrophils. 3-(53-Hydroxymethyl-23furyl)-1-benzyl indazole (YC-1), an activator of sGC, inhibited L-NAME-induced neutrophil TEM. It was interesting that inhibition of neutrophil sGC with 1-H[1,2,4-]oxadiazolo[4,3-a]quinoxalin-1-1 (ODQ) was sufficient to enhance TEM. These results suggest that NO derived from HUVECs acts on neutrophils to inhibit TEM, at least in part by activating sGC. Our findings imply the role of NO constitutively generated by HUVECs in protection against excessive neutrophil extravasation and unnecessary tissue damage under physiological conditions.


Assuntos
Movimento Celular/fisiologia , Células Endoteliais/fisiologia , Neutrófilos/fisiologia , Óxido Nítrico/biossíntese , Veias Umbilicais/fisiologia , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Inibidores Enzimáticos/farmacologia , Humanos , Óxido Nítrico Sintase/antagonistas & inibidores , Veias Umbilicais/citologia
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