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BACKGROUND: Colorectal cancer (CRC) is the second most common solid organ cancer. Traditional treatment is with surgery and chemotherapy. Immunotherapy has recently emerged as a neoadjuvant therapy that could change treatment strategy in both primary resectable and metastatic CRC. METHODS: A literature review of PubMed with a focus on studies exploring upfront immunotherapy in operable CRC, either for primary resectable stage I-III cancers or for (potentially) operable liver metastasis. RESULTS: Immune checkpoint blockade by the programmed cell death 1 (PD-1) receptor inhibitors nivolumab and pembrolizumab and the cytotoxic T cell-associated protein 4 (CTLA-4) inhibitor ipilimumab has shown good results in both early-stage and advanced CRC. The effects of immune checkpoint inhibitors have so far been demonstrated in small phase I/II studies and predominantly in treatment-refractory stage IV disease with defect Mismatch repair (dMMR). However, recent data from phase I/II (NICHE-1) studies suggest an upfront role for immunotherapy in operable stage I-III disease. By blocking crucial immune checkpoints, cytotoxic T cells are activated and release cytotoxic signals that initiate cancer cell destruction. The very high complete response rate in dMMR operable CRC with neoadjuvant immunotherapy with nivolumab and ipilimumab, and even partial pathological response in some patients with proficient MMR (pMMR) CRC, calls for further attention to patient selection for neoadjuvant treatment, beyond MMR status alone. CONCLUSION: Early data on the effect of immunotherapy in CRC provide new strategic thinking of treatment options in CRC for both early-stage and advanced disease, with prospects for new trials.
Immunotherapy has proven to be highly effective as first-line treatment of metastatic colorectal cancer (CRC). Further, immune checkpoint blockade by the programmed cell death 1 (PD-1) receptor inhibitors nivolumab and pembrolizumab and the cytotoxic T cell-associated protein 4 (CTLA-4) inhibitor ipilimumab has provided very good results in both early-stage and advanced CRC. The high response rate in dMMR in operable colon cancers by preoperative use of double nivolumab and ipilimumab therapy warrants further investigation into its impact on long-term overall survival. Hence, immunotherapy has emerged as a neoadjuvant approach, possibly changing treatment strategy for both primary resectable and metastatic CRC. Larger phase III trials are needed to evaluate overall effects on survival.
Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias Retais/tratamento farmacológico , Neoplasias do Colo/patologia , Humanos , Terapia Neoadjuvante , Neoplasias Retais/patologiaRESUMO
The majority of tuberculosis cases in ruminants are caused by Mycobacterium bovis (MB). However, in this study, the authors reported the isolation of Mycobacterium tuberculosis (MT) from bovine milk, nasal swabs and post-mortem tissue samples (n = 841) collected from cattle and buffaloes in the states of Telangana, Maharashtra and Gujarat in India in the period from 2010 to 2015. The isolates (n = 7) were confirmed as Mycobacterium due to their growth characteristics and colony morphology in a commercial liquid medium Mycobacterial Growth Indicator Tube (MGIT)™ employing the BD BACTEC™ MGIT™ 960 system and the Löwenstein-Jensen (LJ) medium supplemented with glycerol but not with sodium pyruvate, and BD-DIFCO™ Middlebrook 7H10 agar containing oleic albumin dextrose catalase (OADC). These isolates were initially identified as members of the M. tuberculosis complex (MTC) using a commercial nested polymerase chain reaction (PCR) kit based on the IS6110 MTC specific nucleotide sequence. The isolates were confirmed as MT using three commercial line probe assay kits, were further genotyped, and the spoligotypes identified were of East African Indian (EAI) 3_IND, EAI5, Central-Asian (CAS) 1_DELHI, U and T1 lineages. Two MT isolates from one antelope (Antilope cervipara) andone gazelle (Gazella bennettii) from Gujarat, which were identified previously, were spoligotyped during this study and identified as belonging to EAI3_IND and EAI5 lineages, respectively. The epidemiological significance and zoonotic implications of regional presence and documentation of the same or two differents poligotypes in different species within the family Bovidae as well as humans is discussed.
La majorité des cas de tuberculose chez les ruminants sont dus à Mycobacterium bovis. Néanmoins, les auteurs rapportent les résultats d'une étude réalisée de 2010 à 2015 en Inde (états de Telangana, Maharashtra et Gujarat), au cours de laquelle Mycobacterium tuberculosis a été isolé à partir de lait de vache ainsi que d'écouvillons nasaux et de prélèvements tissulaires postmortem (n = 841) collectés sur des bovins et des buffles. L'appartenance des isolats au genre Mycobacterium a été confirmée par l'observation des caractéristiques de croissance des colonies et de leur morphologie dans un milieu de culture liquide du commerce (Mycobacterial Growth Indicator Tube [MGIT]™ : tube avec indicateur de croissance mycobactérienne) en utilisant l'automate BD BACTEC™MGIT™ 960 et un milieu de Lowenstein-Jensen additionné de glycérol mais sanspyruvate de sodium, ainsi qu'une gélose BD-DIFCO™ Middlebrook enrichie en acide oléique, albumine, dextrose et catalase (OADC). Dans un premier temps, les isolats ont été identifiés comme étant des membres du complexe M. tuberculosisau moyen d'une amplification en chaîne par polymérase nichée ciblant la séquence nucléotidique spécifique IS6110 du complexe M. tuberculosis. Trois kits commerciaux d'analyse de souches ont permis d'identifier les isolats comme étant M. tuberculosis ; il a ensuite été procédé à l'analyse des génotypes des souches de spoligotypes, lesquelles appartenaient aux lignées East African Indian (EAI) 3_IND,EAI5, Central-Asian (CAS) 1_DELHI, U et T1. Les spoligotypes de deux isolats de M. tuberculosis obtenus précédemment, provenant respectivement d'une antilope(Antilope cervipara) et d'une gazelle (Gazella bennettii) de l'état de Gujarat ont été analysés lors de la présente étude et identifiés comme étant respectivement de lignée EAI3_IND et EAI5. Les auteurs analysent l'importance épidémiologique et la portée zoonotique de la présence rapportée dans la région du même spoligotype ou de deux spoligotypes différents chez des espèces différentes de la famille des Bovidés ainsi que chez l'homme.
La mayoría de los casos de tuberculosis que afectan a los rumiantes son causados por Mycobacterium bovis (MB). En este estudio, sin embargo, los autores dan cuenta del aislamiento de Mycobacterium tuberculosis (MT) en muestras de leche, frotis nasales y tejidos obtenidos post-mortem (n = 841) de ganado vacuno y búfalos de los estados de Telangana, Maharashtra y Gujarat (India) entre 2010 y 2015. Se confirmó que los microorganismos aislados(n = 7) eran micobacterias por sus características de crecimiento y la morfología de las colonias cultivadas en medio líquido comercial Mycobacterial Growth Indicator Tube (MGIT)™ empleando el sistema BD BACTEC™ MGIT™ 960 y el medio Löwenstein-Jensen (LJ) suplementado con glicerol, pero no con piruvato sódico, y agar BD-DIFCO™ Middlebrook 7H10 con ácido oleico, albúmina, dextrosa y catalasa (OADC). Mediante una PCR (reacción en cadena de la polimerasa) anidada comercial basada en la secuencia nucleotídica IS6110 específica del complejo, se empezó por determinar que esos microorganismos pertenecían al complejo M. tuberculosis (MTC). Tras confirmar que se trataba de M. tuberculosis empleando tres ensayos comerciales con sondas en línea, se procedió a caracterizar su genotipo, lo que sirvió para identificar espoligotipos correspondientes a los siguientes linajes: East African Indian (EAI) 3_IND, EAI5, Central-Asian (CAS) 1_DELHI, U y T1. Durante el estudio se caracterizaron asimismo los espoligotipos de dos M. tuberculosis aislados previamente a partir de un antílope (Antilope cervipara) y una gacela (Gazella bennettii) de Gujarat, lo que permitió adscribirlos respectivamente a los linajes EAI3_IND y EAI5. Los autores exponen la importancia desde el punto de vista epidemiológico que tiene la presencia comprobada en la región del mismo espoligotipo o de dos espoligotipos diferentes en distintas especies de la familia Bovidae, así como en el ser humano, y las consecuencias que de ahí se siguen por lo que respecta a posibles zoonosis.
Assuntos
Mycobacterium tuberculosis , Tuberculose , Animais , Bovinos , Humanos , Índia , Epidemiologia Molecular , Mycobacterium bovis , Ruminantes , Tuberculose/veterináriaRESUMO
Multiplex reverse-transcription polymerase chain reaction (mRT-PCR) assay is a sensitive and rapid method for the detection and serotyping of foot and mouth disease virus (FMDV). However, the method has not been used to its full potential, because of factors such as cost, a lack of infrastructure and the complexity of the reaction mixture. This study was undertaken to optimise and validate a thermostable, lyophilised, ready-to-use mRT-PCR kit for the rapid detection of FMDV in field laboratories in India. Trehalose, PEG-8000 and glycerol were evaluated for stabilisation of the PCR mixture at ambient temperatures. The lyophilised mRT-PCR kit was validated and found robust enough for use in field-level laboratories. The PCR reaction mixture in the ready-to-use kit has low complexity, so chances of cross-contamination during the preparation of the mixture are limited, but may easily be monitored by using lyophilised internal positive and negative controls. In addition, the requirement to maintain live FMDV isolates as internal positive controls at field-level regional laboratories is eliminated.
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Vírus da Febre Aftosa/classificação , Vírus da Febre Aftosa/isolamento & purificação , Reação em Cadeia da Polimerase Via Transcriptase Reversa/veterinária , Sorotipagem/métodos , Animais , RNA Viral/isolamento & purificação , Reprodutibilidade dos Testes , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Allergy to supplemental lactase is sparsely reported in the literature with only one prior case of anaphylaxis documented [2]. Reactions to this agent can occur following cow's milk ingestion which could lead to an erroneous diagnosis of cow's milk allergy in the absence of another explanation. CASE PRESENTATION: Our patient, a 48-year-old male with eczema, exercise-induced asthma and rhinoconjunctivitis, presented with four episodes of systemic reactions characterized by mucosal swelling and asthma symptoms following ice-cream exposure. It was later recognized that he had been taking a lactase enzyme supplement just prior to all of his reactions. Epicutaneous testing was strongly positive to a saline slurry of the lactase supplement he had been using. The patient has been avoiding supplemental lactase since with no subsequent reactions. DISCUSSION: Our patient was diagnosed with an allergy to supplemental lactase enzyme on the basis of convincing Immunoglobulin E (IgE) mediated symptoms and positive skin testing. He continued to eat cow's milk products, ruling out an IgE-mediated allergy to cow's milk. In the literature, there is one prior case of anaphylaxis documented. Another case of localized oropharyngeal symptoms described in the literature was thought to be a form of oral allergy syndrome as the patient had positive epicutaneous testing to Aspergillus oryzae-derived lactase as well as Aspergillus species. Occupational sensitization, rhinitis/asthma, and protein contact dermatitis have also been detailed in the literature. Although rare, this case highlights the importance of a thorough history of over-the-counter supplements when assessing a patient with features of anaphylaxis.
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A highly contagious virus infection in horses, influenza is the single most important equine respiratory disease in the world. This paper presents details of a one-year study (1 June 2008 to 31 May 2009) to determine the prevalence of equine influenza in the horses of Gujarat State in India. The prevalence of equine influenza A/equi-2 was 12.02%, but none of the samples were positive for equine influenza A/equi-1. The prevalence of equine influenza (A/equi-2) was 15.38%, 11.94%, 10.18%, and 9.09% in horses of the Kathiyawari breed, a non-descript breed, the Marwari breed and the Indian Thoroughbred breed, respectively. The highest prevalence of influenza was observed in yearlings (17.48%) and prevalence was at its highest in the month of April (28.89%). The prevalence rate in males, females and geldings was 11.95%, 10.38% and 8.47%, respectively. The mortality rate and case fatality rate were 1.28% and 10.64%, respectively.
Assuntos
Doenças dos Cavalos/epidemiologia , Vírus da Influenza A Subtipo H3N8 , Infecções por Orthomyxoviridae/veterinária , Distribuição por Idade , Animais , Anticorpos Antivirais/sangue , Feminino , Testes de Inibição da Hemaglutinação/veterinária , Testes de Hemaglutinação/veterinária , Doenças dos Cavalos/virologia , Cavalos , Índia/epidemiologia , Vírus da Influenza A Subtipo H3N8/imunologia , Vírus da Influenza A Subtipo H7N7/imunologia , Masculino , Infecções por Orthomyxoviridae/epidemiologia , Prevalência , Distribuição por SexoRESUMO
AIM: The present study aimed to study the seroprevalence of brucellosis in small ruminants of Gujarat state, India, using Rose Bengal Plate test (RBPT) and indirect enzyme-linked immunosorbent assay (iELISA). MATERIALS AND METHODS: A total of 2444 sera samples (675 sheep and 1769 goat) from unorganized sector and 1310 sera samples (861 sheep and 449 goat) from seven organized farms were collected for brucellosis screening. RESULTS: In unorganized sector, 23.70% sheep (160/675) and 15.99% goat (283/1769) were positive by RBPT and 24.44% sheep (165/675) and 17.24% goat (305/1769) by iELISA. The organized sector samples showed higher seroprevalence in goat (7.79 %, 35/449) than sheep (4.06 %, 35/861) by RBPT. Similarly, in iELISA, goat samples showed a higher seroprevalence (9.35%, 42/449) compared to sheep (7.50%, 65/861). The diagnostic sensitivity and specificity of RBPT with ELISA were 88.69% and 99.65%, respectively, and showed a significant difference (p≤0.0001). The Chi-square analysis revealed a significant difference in seroprevalence between sectors (p≤0.01) and species (p≤0.01). CONCLUSION: The seroprevalence of brucellosis in small ruminants of Gujarat was investigated and showed a higher prevalence of brucellosis and warrants the implementation of proper preventive measures.
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We have examined granulocytes from patients with chronic myelogenous leukemia (CML) and from normal subjects to determine whether activity of a specific sialyltransferase might account for the aberrant sialylation of O-linked membrane oligosaccharides in CML cells. Total membrane preparations of morphologically mature CML and normal granulocytes were tested for sialyltransferase activity using the substrates galactosyl-beta 1-3-N-acetyl-D-galactosamine-alpha-O-nitrophenyl and N-acetyl-D-galactosamine-alpha-phenyl. N-Acetyl-D-galactosamine-alpha-phenyl was not an acceptor with either CML or normal cells. With galactosyl-beta 1-3-N-acetyl-D-galactosamine-alpha-O-nitrophenyl, sialyltransferase activity was 2.8 times higher in CML cells compared to normal cells. Product identification by high performance liquid chromatography showed that enzyme from both normal and CML granulocytes linked sialic acid to galactosyl-beta 1-3-N-acetyl-D-galactosamine-R by the alpha(2-3) and not the alpha(2-6) linkage. The enzyme CMP-N-acetylneuraminic acid: galactosyl-beta 1-3-N-acetyl-D-galactosamine-R alpha(2-3)-sialyltransferase has not previously been described in human granulocytes. The marked increase in activity of this enzyme in CML and the resulting increase in sialylation may contribute to the pathophysiological behavior of CML granulocytes.
Assuntos
Granulócitos/enzimologia , Leucemia Mieloide/enzimologia , Sialiltransferases/metabolismo , Proteínas Anticongelantes , Sequência de Carboidratos , Galactose/metabolismo , Glicoproteínas/metabolismo , Humanos , Membranas/enzimologia , Especificidade por Substrato , beta-Galactosídeo alfa-2,3-SialiltransferaseRESUMO
We have examined the role of CMP-NeuAc:Gal beta 1-3GalNAc-R alpha(2-3)-sialyltransferase in fresh leukemia cells and leukemia-derived cell lines. Enzyme activity in normal granulocytes using Gal beta 1-3GalNAc alpha-o-nitrophenyl as substrate was 1.5 +/- 0.7 nmol/mg/h whereas activity in morphologically mature granulocytes from 6 patients with chronic myelogenous leukemia (CML) was 4.2 +/- 1.6 nmol/mg/h (P less than 0.05). Myeloblasts from 5 patients with CML in blast crisis showed enzyme activity levels of 6.5 +/- 2.5 nmol/mg/h. From 2 patients with CML, both blasts and granulocytes were obtained, with higher enzyme activity in the patients' blasts (7.1 nmol/mg/h) than in their granulocytes (4.9 nmol/mg/h) in both cases, suggesting that the increase in enzyme activity is related to the differentiation or proliferation status of the CML cells. However, similarly high enzyme levels were also seen in myeloblasts from acute myeloblastic leukemia patients (5.6 +/- 1.4 nmol/mg/h) and in some acute myeloblastic leukemia-derived cell lines (KG1a and HL60), suggesting that increased levels of this enzyme are not directly correlated with the presence of the Ph1 chromosome. This alpha(2-3)-sialyltransferase activity can also be detected in normal peripheral blood lymphocytes and exhibits increased activity in chronic lymphocytic leukemia cells and acute lymphoblastic leukemia. These data suggest that the level of enzyme activity may vary with growth rate and maturation status in myeloid and lymphoid hemopoietic cells. Finally, we have identified a glycoprotein in acute myeloblastic leukemia cells that serves as a substrate for the alpha(2-3)-sialyltransferase. The desialylated form of the glycoprotein was resialylated in vitro by the purified placental form of this alpha(2-3)-sialyltransferase and exhibits a molecular weight of about 150,000.
Assuntos
Granulócitos/enzimologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/enzimologia , Leucemia Mieloide Aguda/enzimologia , Sialiltransferases/metabolismo , Células Tumorais Cultivadas/enzimologia , Crise Blástica/enzimologia , Linhagem Celular , Humanos , Cinética , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Linfócitos/enzimologia , Valores de Referência , beta-Galactosídeo alfa-2,3-SialiltransferaseRESUMO
The objectives of this paper were calculation and comparison of the effective doses, the risks of exposure-induced cancer, and dose reduction in the gonads for male and female patients in different projections of some X-ray examinations. Radiographies of lumbar spine [in the eight projections of anteroposterior (AP), posteroanterior (PA), right lateral (RLAT), left lateral (LLAT), right anterior-posterior oblique (RAO), left anterior-posterior oblique (LAO), right posterior-anterior oblique (RPO), and left posterior-anterior oblique (LPO)], abdomen (in the two projections of AP and PA), and pelvis (in the two projections of AP and PA) were investigated. A solid-state dosimeter was used for the measuring of the entrance skin exposure. A Monte Carlo program was used for calculation of effective doses, the risks of radiation-induced cancer, and doses to the gonads related to the different projections. Results of this study showed that PA projection of abdomen, lumbar spine, and pelvis radiographies caused 50%-57% lower effective doses than AP projection and 50%-60% reduction in radiation risks. Also use of LAO projection of lumbar spine X-ray examination caused 53% lower effective dose than RPO projection and 56% and 63% reduction in radiation risk for male and female, respectively, and RAO projection caused 28% lower effective dose than LPO projection and 52% and 39% reduction in radiation risk for males and females, respectively. About dose reduction in the gonads, using of the PA position rather than AP in the radiographies of the abdomen, lumbar spine, and pelvis can result in reduction of the ovaries doses in women, 38%, 31%, and 25%, respectively and reduction of the testicles doses in males, 76%, 86%, and 94%, respectively. Also for oblique projections of lumbar spine X-ray examination, with employment of LAO rather than RPO and also RAO rather than LPO, demonstrated 22% and 13% reductions to the ovaries doses and 66% and 54% reductions in the testicles doses, respectively.
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BACKGROUND: The aim of this study was identification of the epidemiology of Prototheca zopfii species from the milk samples of dairy cattle in Isfahan, central Iran. METHODS: Milk samples were obtained from 230 dairy cattle, 130 with and 100 without mastitis, in Isfahan. The samples were cultured in Prototheca Isolation Medium (PIM) and Sabouraud's dextrose agar. All P. zopfii isolates were identified by morphological and biochemical methods. Then, as a confirmatory test they were examined by genotype-specific PCR. RESULTS: Four P. zopfii strains (3.07%) were isolated from the 130 samples of dairy cattle with clinical mastitis and there was no isolation from totally 100 samples of healthy bovines without mastitis. Specific PCR product (about 946 bp) was detected in four isolates. CONCLUSION: It seems that P. zopfii genotype II plays a key role in affecting bovine mastitis that confirmed other previous studies. Our study was the first, which identified the Prototheca species by traditional and molecular methods in Iran and Middle East as well.
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Chitosan-poly(vinyl alcohol) (Cs:PVA) nanofibrous scaffolds were electrospun from 2:3 (wt/wt) Cs:PVA solution dissolved in 80% acetic acid. In vivo study was carried out on the dorsum skin of rat which burnt with a hot brass cylinder. The scaffolds were applied in two forms, that is, acellular (n=6) and cell-seeded with mesenchymal stem cells (n=6). Macroscopic measurements of wound area showed good aspect healing effect of scaffolds in comparison with control wounds specially in 15 days post operating. Pathological studies were done on the wounds to investigate the healing effects. The healing process of the wound covered with Cs/PVA nanofibrous scaffolds was much rapid compared to untreated wounds. However, the presence of stem cells on this scaffolds accelerated the wound healing process owing to their ability of collagen regeneration.
Assuntos
Queimaduras/terapia , Quitosana/química , Nanoestruturas/química , Pele/lesões , Transplante de Células-Tronco/instrumentação , Engenharia Tecidual/instrumentação , Alicerces Teciduais , Animais , Bandagens , Queimaduras/patologia , Quitosana/uso terapêutico , Procedimentos Cirúrgicos Dermatológicos/métodos , Desenho de Equipamento , Análise de Falha de Equipamento , Masculino , Nanoestruturas/uso terapêutico , Álcool de Polivinil/química , Álcool de Polivinil/uso terapêutico , Ratos , Ratos Sprague-Dawley , Pele/patologia , Resultado do TratamentoRESUMO
Chitosan-polyvinyl alcohol (PVA) blend nanofibrous webs were fabricated in different blend ratios through electrospinning procedures. From scanning electron microscopy (SEM) results, 25/75 blend ratio of chitosan-PVA was selected for biological studies. In vivo studies were carried out on the dorsum of rats of two types: longitudinal incisional wounds (n=8 rats) and round excisional wounds (n=8). Pathological study was done on the wounds to investigate the healing process. The histological study in wound healing indicated that the administration of chitosan nanofibrous web improved the wound healing, qualitatively and quantitatively.
Assuntos
Bandagens , Quitosana/uso terapêutico , Nanoestruturas/uso terapêutico , Álcool de Polivinil/uso terapêutico , Cicatrização/fisiologia , Ferimentos Penetrantes/patologia , Ferimentos Penetrantes/terapia , Animais , Materiais Biocompatíveis/uso terapêutico , Masculino , Teste de Materiais , Ratos , Ratos Sprague-Dawley , Resultado do TratamentoRESUMO
explain this tendency to develop infections. A decrease in the number and function of CD8+ suppressor/cytotoxic T cells from peripheral blood of AD patients has been reported.2 This could explain the increased incidence of cutaneous viral and fungal infections observed in these patients. Monocytes from AD patients secrete increased levels of interleukin (IL)-10 that can inhibit T cell mediated responses.3 Leukocytes from patients with AD have been found to produce decreased amounts of interferon gamma (IFN-g),4 which is required for the
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Dermatite Atópica/etiologia , Infecções/complicações , Dermatite Atópica/imunologia , HumanosRESUMO
Granulocytes from patients with chronic myelogenous leukaemia (CML) have been previously shown to have aberrant sialylation of membrane glycoproteins. We have examined the granulocytes from CML patients receiving intermittent chemotherapy to determine the relationship of the oligosaccharide changes to treatment. Compared to cells from non-leukaemic patients, granulocytes from untreated CML patients showed less adherence to nylon wool, decreased reactivity with peanut lectin, and decreased binding of the synthetic chemotactic peptide formyl-methionine-leucine-phenylalanine (FMLP). Granulocytes from CML patients treated with chemotherapy showed nylon wool adherence, peanut lectin reactivity and FMLP binding comparable to non-leukaemic cells. Chemotherapeutic agents may interfere with oligosaccharide synthesis with a resulting change in the composition of cell surface glycoconjugates.
Assuntos
Granulócitos/efeitos dos fármacos , Leucemia Mieloide/tratamento farmacológico , Testes de Aglutinação , Adesão Celular , Agregação Celular/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Humanos , Lectinas/metabolismo , Lectinas/farmacologia , Leucemia Mieloide/sangue , N-Formilmetionina Leucil-Fenilalanina/metabolismo , N-Formilmetionina Leucil-Fenilalanina/farmacologia , Aglutinina de AmendoimRESUMO
Granulocytes from patients with chronic myelogenous leukemia (CML) are morphologically identical to their normal counterparts but show marked differences in circulation patterns and in some membrane properties. We have previously shown that there is abnormal lectin binding to CML granulocytes, and aberrant sialylation of membrane glycoproteins. To examine the changes in sialylation of CML granulocytes further, we have studied membrane preparations from CML and normal granulocytes for specific sialyltransferase activity. Because sialyltransferase enzymes are specific for the configuration of the acceptor group, enzyme activity was assayed by measuring transfer of sialic acid from CMP-14C-sialic acid to substrates of defined structure. As compared with those of normal counterparts, CML extracts catalyzed a 50% higher overall rate of sialylation of asialofetuin, a substrate possessing both N- and O-linked acceptors. Studies of enzyme specificity utilizing porcine and ovine submaxillary mucins, antifreeze glycoprotein and alpha-1 acid glycoprotein as acceptors showed that the increased sialylation by CML extracts was due primarily to substrates with the O-linked Gal beta 1----3GaINAc acceptor group. These data suggest that sialyltransferase activity is increased in CML granulocytes compared to normal granulocytes and that the increased enzyme activity is specific for O-linked Gal beta 1----3GaINAc. This enzyme activity may be directly responsible for the abnormal membrane sialylation and pathophysiological behavior of these cells.