Genetically modified organisms: adapting regulatory frameworks for evolving genome editing technologies

Genetic modification of living organisms has been a prosperous activity for research and development of agricultural, industrial and biomedical applications. Three decades have passed since the first genetically modified products, obtained by transgenesis, become available to the market. The regulatory frameworks across the world have not been able to keep up to date with new technologies, monitoring and safety concerns. New genome editing techniques are opening new avenues to genetic modification development and uses, putting pressure on these frameworks. Here we discuss the implications of definitions of living/genetically modified organisms, the evolving genome editing tools to obtain them and how the regulatory frameworks around the world have taken these technologies into account, with a focus on agricultural crops. Finally, we expand this review beyond commercial crops to address living modified organism uses in food industry, biomedical applications and climate change-oriented solutions.

Efeito do uso de minerais traços (cobre, zinco, selênio e manganês) e vitaminas (A e E) injetáveis sobre o estresse oxidativo e função de neutrófilos de fêmeas da raça Holandesa no período de transição / Effect of use of injected trace minerals (copper, zinc, selenium, and manganese) and vitamins (A and E) on oxidative stress and neutrophil function in females of Hostein cows during transitionl

O objetivo deste estudo foi avaliar o efeito metafilático de minerais traços e vitaminas A e E injetáveis, em parâmetros do estresse oxidativo e na função de neutrófilos em fêmeas da raça Holandesa no período de transição. Sessenta animais foram divididos em dois grupos: animais que receberam minerais traços e vitaminas A e E injetáveis (GMTV) (n= 30) e grupo controle (GC) (n= 30). Não houve diferença significativa entre os grupos nos parâmetros avaliados, porém observou-se diferença significativa entre tratamento e dia para os valores da SOD, com maior atividade dessa enzima em fêmeas GMTV, nas semanas próximas ao parto. Observou-se diferença de dia e para interação tratamento e dia para o TBARS, em que fêmeas GMTV mostraram menores valores de TBARS em todos os momentos, exceto sete dias após o parto. Houve efeito significativo de dia para leucócitos, interação tratamento e dia para neutrófilos e interação tratamento e dia para fagocitose de neutrófilos, em que as fêmeas GMTV apresentaram valores menores de leucócitos e neutrófilos próximo ao parto, além de maior fagocitose de neutrófilos. Pode-se observar que houve melhora no sistema oxidativo e imune de fêmeas GMTV, resposta que provavelmente está relacionada com a administração dos minerais traços e vitaminas A e E.(AU)

This study evaluates the metaphylactic of the subcutaneous administration of a trace minerals and vitamins A and E, on the oxidative stress and neutrophil function in Holsteins cows under the transition period. Sixty females were divided in two groups: group with trace minerals and vitamins (GMTV) (n= 30) and group control (GC) (n= 30). There was no significant difference between those groups; however, we find significant difference between treatment and day for Superoxide dismutase (SOD) values with higher activity of this enzyme in females GMTV on the weeks next to the parturition. Still, there was difference on day and, for interactions between treatment and day for TBARS, were females GMTV showed lower values of TBARS in all moments, except on day seven after the parturition. For leucocytes, there is a significant effect by day, interaction on treatment and day on neutrophils, and interaction treatment and day for neutrophil phagocytosis, were females GMTV showed lower values of leucocytes and neutrophils next to the parturition, and an increase of neutrophils phagocytosis. In summary, cows from the GMTV group had an improvement on the immune and oxidative systems, probably correlated with the administration of this supplement.(AU)

Estallido respiratorio de neutrófilos por las técnicas del nitroazul tetrazolio (NBT) y dihidrorodamina (DHR) en niños con sospecha clínica de enfermedad granulomatosa crónica (EGC)

Introducción: El estallido respiratorio (ER) de neutrófilos es fundamental para la defensa contra infecciones, proceso ausente o ineficaz en la EGC, una inmunodeficiencia primaria (IDP) diagnosticada mediante la prueba del NBT. Actualmente se destacan las técnicas por citometría de flujo como la DHR, realizada únicamente en el Instituto de Investigaciones en Ciencias de la Salud (IICS), habiendo sido aplicada sólo en niños sanos. Objetivo: Evaluar el ER de neutrófilos por las técnicas NBT y DHR en niños con sospecha clínica de EGC y describir sus características clínico-demográficas. Materiales y Métodos: Se incluyeron 36 niños de ambos sexos, menores de 17 años de edad, remitidos al IICS entre el 2014-2015 por médicos especialistas. Se extrajo sangre para evaluación del ER de neutrófilos y se aplicó un cuestionario. Resultados: La mediana de edad fue de 4 años, 56% varones. Predominaron los pacientes hospitalizados, la sepsis y forunculosis cutánea fueron las manifestaciones clínicas más frecuentes y un 72% presentó recurrencia de infecciones con mediana de 3 episodios/año. El promedio para el IE de neutrófilos fue de 38,1±13,7 en el ensayo DHR, y 87±17% de activación para la prueba del NBT. En 8 pacientes los valores fueron inferiores al considerado normal y en un niño se confirmó EGC, observándose un patrón de herencia ligada al X. Conclusión: La evaluación del ER de neutrófilos permitió detectar un caso de EGC, determinándose el patrón hereditario mediante la técnica DHR por primera vez en el país. Es esencial el empleo de herramientas diagnósticas disponibles en niños con sospecha clínica de IDPs, para la detección y tratamiento oportunos que mejoran su calidad de vida y reducen la mortalidad.

Introduction: The neutrophil`s respiratory burst (RB) is essential for the defense against infections, this process is absent or ineffective in the CGD, a primary immunodeficiency (PID) diagnosed by the NBT test. Techniques that used flow cytometry such as DHR, performed only at the Instituto de Investigaciones en Ciencias de la Salud (IICS), currently stand out, having been applied only to healthy children. Objective: To evaluate the neutrophil`s RB using the NBT and DHR techniques in children with clinical suspicion of CGD and to describe their clinical and demographic characteristics. Materials and methods: 36 children of both sexes, with less than 17 years of age, that were referred to the IICS by specialists physicians between the years 2014-2015 were included. A blood sample was obtained to evaluate the neutrophil`s RB and a questionnaire was applied. Results: The median age was of 4 years and 56 % were males. Predominantly the patients were hospitalized, being sepsis and cutanueos furunculosis the most frequent clinical manifestations and a 72 % presented recurrent infection with a median of 3 episodes/year. The average for the neutrophil´s stimulation index (EI) was 38,1±13,7 with the DHR test, and 87±17% of activation for the NBT test. In 8 patients the values obtained were below the ones considered as normal and in one child CGD was confirmed, in which an X-linked inheritance pattern was observed. Conclusion: The evaluation of the neutrophil`s RB allowed the detection of one case of CGD, and the inheritance pattern was determined by the DHR test for the first time in our country. The use of available diagnostic tools in children with clinical suspicion of PID is essential for the appropriate detection and treatment that improve the quality of life and reduce mortality.

Application of tissue spontaneous fluorescence in myocardial ischemia injury of rats / 中国药理学通报

Aim Todiscusstheapplicationoftissue spontaneous fluorescence in myocardial ischemia injury of rats based on specific fluorescence detection technol-ogy.Methods Thechangeofspontaneousfluores-cence was compared between the myocardial tissue of normal rats and those of rats with myocardial ischemia injury and an quantitative analysis was then made.Re-sult Theresultsshowedthatspontaneousfluorescence of myocardial tissue for myocardial ischemia injury changed significantly.Spontaneous fluorescence signal of injury considerably was enhanced.The fluorescence signal which was quantified by FX Pro had statistical significance compared with normal myocardial tissue,P<0.01orP<0.05.Conclusion Ourresearchshows that spontaneous fluorescence of myocardial tissue can be enhanced obviously after myocardial ischemia inju-ry.Our research provides a method for the research and evaluation of myocardial ischemia injury model in rats which can be used in positioning,qualitative and quan-titative comparative study and in pathological,physio-logical,pharmacological and mechanism study.

Leucograma e metabolismo oxidativo de neutrófilos em cabras da raça Saanen nos períodos de gestação, parto e pós-parto / Leukocyte count and neutrophil oxidative burst in Saanen goats in the pregnancy, parturition and postpartum periods

O presente estudo teve como objetivo a avaliação do leucograma e do metabolismo oxidativo de neutrófilos em fêmeas caprinas da raça Saanen, nos períodos de gestação, parto e pós-parto. Amostras de sangue foram colhidas de 20 fêmeas nulíparas da raça Saanen, clinicamente sadias por venipunção jugular aos 49 (M1), 42 (M2), 35 (M3), 28 (M4), 21 (M5), 14 (M6), sete (M7), três (M8) dias antes do parto, no dia do parto (M9), três (M10) e sete (M11) dias após o parto, para a realização do leucograma e dosagens séricas de cortisol, estradiol e progesterona. A partir de 28 dias (M4) antes do parto até sete dias do pós-parto (M11) foram colhidas amostras de sangue para a avaliação do metabolismo oxidativo de neutrófilos por meio do teste de redução do tetrazólio nitroazul (NBT). Os resultados demonstraram que no dia do parto houve aumento nas concentrações séricas de cortisol e estradiol, e diminuição da progesterona, leucocitose por neutrofilia e desvio à esquerda leve, diminuição dos linfócitos, aumento da relação neutrófilo:linfócito, eosinopenia, monocitose e basofilia. No sétimo dia do pós-parto houve leucocitose por neutrofilia e aumento da relação neutrófilo:linfócito. Não houve nos períodos de gestação, parto e pós-parto alterações significativas no metabolismo oxidativo dos neutrófilos. Conclui-se que o parto determina elevação da concentração sérica de cortisol e estradiol, e diminuição da progesterona determinando quadro de leucocitose por neutrofilia e desvio à esquerda leve, com diminuição dos linfócitos, aumento da relação neutróflo:linfócito, eosinopenia, monocitose e basofilia. Ao sétimo dia do pós-parto há leucocitose por neutrofilia, aumento da relação neutrófilo:linfócito e do fibrinogênio. A gestação, o parto e o período do pós-parto não alteram o metabolismo oxidativo de neutrófilos avaliado por meio do teste de redução do NBT.

The purpose of this study was to evaluate the leukocyte count and the oxidative metabolism of neutrophil in Saanen goats during periods of pregnancy, parturition and postpartum. Were used 20 Saanen goats, clinically healthy and serologically negative for caprine arthritis encephalitis virus (CAEV). Blood samples were collected by jugular venipuncture 49 (M1), 42 (M2), 35 (M3), 28 (M4), 21 (M5), 14 (M6), seven (M7), three (M8) days before the parturition, on the day of birth (M9), three (M10) and seven (M11) days postpartum, for the leukocyte count, and serum for cortisol, estradiol and progesterone determination. From 28 days (M4) before parturition until seven days postpartum (M11) blood samples were collected for evaluation of oxidative metabolism of neutrophils by the nitroblue tetrazolium reduction test (NBT). The results showed that at parturition day there were an increase in cortisol and estradiol levels and a decrease in progesterone serum, neutrophilic leukocytosis and left shift slight, decrease of lymphocytes, increase in the neutrophil: lymphocyte, eosinopenia, monocytosis and basophilia. There was a neutrophilic leukocytosis and an increase in the neutrophil: lymphocyte on the seventh day postpartum. There were not significant alterations in oxidative metabolism of neutrophils during pregnancy, parturition and postpartum. It was concluded that parturition causes an elevation in cortisol and estradiol levels and a decrease in progesterone serum determining a neutrophilic leukocytosis and left shift slight, with a reduction of lymphocytes, increase in the neutrophil:lymphocyte, eosinopenia, monocytosis and basophilia. Neutrophilic leukocytosis, increase in the neutrophil: lymphocyte and fibrinogen are detected on the seventh day postpartum. Pregnancy, parturition and the postpartum do not change the oxidative metabolism of neutrophils evaluated by NBT reduction test.

Determination of the activity of PEOZ liposomal SOD mimic using NBT-Illumination method / 中国药学杂志

OBJECTIVE: To establish the method for determinating the activity of [poly(2-ethyl-2-oxazoline), PEOZ]-modified liposomes encapsulated superoxide dismutase (SOD) mimic (PEOZ-L-SOD). METHODS: PEOZ-L-SOD was prepared by film dispersion method, and the activities of the SOD mimic and PEOZ-L-SOD were determined by NBT-Illumination method. RESULTS: The fitted equation of the inhibition rate curve of the SOD mimic was IR%=33.4211nρ + 49.715 (r2=0.9992) and the IC50 was 1.0086 × 10-3 μmol · L-1; the fitted equation of the inhibition rate curve of PEOZ-L-SOD was IR%=33.5211nρ + 49.671 (r2=0.9991) and the IC50 was 1.0099 × 10-3 μmol · L-1. CONCLUSION: The NBT-Illumination method is simple, reliable, economic and practical, and can be used as an efficient method to determine the activity of SOD mimic liposomes. The experiment proves that the activity of SOD mimic did not change after it was encapsulated in the liposomes.

Metabolismo oxidativo de heterófilos de avestruzes jovens / Oxidative metabolism by heterophils from young ostriches

Foi avaliada a hipótese que, à semelhança dos neutrófilos de mamíferos, a produção de superóxido pelos heterófilos de avestruzes está associada com a maturidade funcional dessas células. Foram utilizados 20 avestruzes de ambos os sexos, divididos em dois grupos: 1--30 dias (n=10) e 180--240 dias (n=10) de idade. Para avaliação do metabolismo oxidativo dos heterófilos, estimou-se a produção de superóxido, utilizando o teste citoquímico não estimulado de redução do tetrazólio de nitroazul (NBT). A porcentagem média de redução heterofílica do NBT de avestruzes com até 30 dias de idade (0,7±1,3) foi menor (P<0,001) que a observada naqueles com idade entre seis e oito meses (6,2±2,7). Conclui-se que o metabolismo oxidativo dos heterófilos de avestruzes aumenta com a idade, sugerindo que essa menor produção de superóxido reduz a capacidade bactericida e pode contribuir para a alta mortalidade nos três primeiros meses de vida.

It was valuated the hypothesis that, like the neutrophils of mammals, the superoxide production by avian heterophils is associated with functional maturity of these cells. Were used twenty ostriches of both sexes, divided into two groups: 1--30 days (n=10) and 180--240 days (n=10) of age. The oxidative metabolism by heterophils was estimated by superoxide production in not stimulated cytochemic test of nitroblue terazolium (NBT). The average percentage of heterophilic NBT reduction in ostriches with up to 30 days of age (0.7±1,3) was lower (P<0,001) than that observed in those aged between six and eight months (6,2±2,7). It was concluded that the oxidative metabolism by ostriches' heterophils increases with age, suggesting that lower superoxide production reduces the ability bactericide and may contribute to high mortality in the first three moths of life.

Comparative study of NBT reduction method for estimation of glycated protein (serum fructoseamine) with glycated hba1c estimated on DCA 2000+analyzer (immunoagglutination inhibition).

Glycated protein estimation is a diagnostic tool, used for the long term and short term monitoring of the glycemic status of diabetic patients. The present study is designed to compare and correlate modified NBT reduction method for the estimation of Glycated protein (serum fructosamine) with HbA1c estimated on DCA+2000 Analyzer. Glycated protein (serum fructosamine) reduces Nitro Blue Tetrazolium (NBT) reagent in alkaline medium to tetrazinolyl radical NBT+ which forms a highly colored monoformazen compound, absorbance of which is directly proportional to the concentration of glycated protein (serum fructosamine) present in the sample and is recorded as ΔA/min. The results of modified NBT were then compared with HbA1c estimated by immunoagglutination inhibition method. Correlation coefficient between HbA1c with serum fructosamine was found to be r = 0.739 using Schimadzu CL-750 spectrophotometer and r = 0.731 using colorimeter. Results of this study were found to be statistically significant P<0.001. Hence this method could be used for routine monitoring of blood glucose control in diabetics as HbA1c estimation.

Metabolismo oxidativo dos neutrófilos de bezerros das raças Nelore e Limousin nos primeiros quatro meses de vida / Neutrophil oxidative burst in Nelore and Limousin calves in the first four months of life

To study some defence mechanisms of beef calves kept on range conditions, 90 healthy calves, 45 Nelore and 45 Limousin, were bled at 24 to 36 hours of life, 15, 30, 60, 90 and, 120 days. Leukogram and neutrophil oxidative burst through the non-stimulated and the stimulated NBT tests were determined. The parasitemia with Anaplasma marginale, Babesia bigemina and B. bovis was investigated. Repeated measure ANOVA was used to analyse the age effect on leukocyte counts. Variation of positive neutrophil throughout the age was analysed through Krushkal-Wallis test. Comparisons among breeds were done using the Mann-Whithney test. The white blood cell count increased with age in both breeds, with a decrease in neutrophil and an increase in lymphocyte counts. The neutrophil lymphocyte ratio had been inverted before 15 days of life. The neutrophil oxidative burst was less effective in the newborn calves increasing with age. Limousin calves' neutrophils had higher capacity to reduce NBT in advanced ages. The observed differences between taurine and Zebu calves had no effects on calves' health and could be atributed to Anaplasma marginale natural and asynptomatic infection.

Com o objetivo de investigar alguns mecanismos de defesa em bezerros de raças de corte criadas a campo, foram utilizados 90 animais recém-nascidos aparentemente sadios, 45 da raça Nelore e 45 da raça Limousin. Amostras de sangue foram colhidas de cada bezerro entre 24 e 36 horas de vida e aos 15, 30, 60, 90 e 120 dias. Determinaram-se o leucograma e o metabolismo oxidativo dos neutrófilos por meio do teste da redução do tetrazólio de nitroazul (NBT), provas não estimulada (NBT-NE) e estimulada (NBT-E). Investigou-se a taxa de parasitemia determinada por Anaplasma marginale, Babesia bigemina e B. bovis. Utilizou-se a análise de variância de medidas repetidas para estudar o comportamento das variáveis hematológicas com o avançar da idade. O teste de Krushkal-Wallis foi empregado para caracterizar a variação da porcentagem de neutrófilos reativos relacionada à idade. Comparações entre as raças foram realizadas em cada idade por meio do teste de Mann-Whithney. A contagem total de leucócitos aumentou com a idade nas duas raças estudadas. Observou-se diminuição do número de neutrófilos e aumento do de linfócitos, ocorrendo sua inversão antes dos 15 dias de idade. A capacidade oxidativa dos neutrófilos foi menor nos bezerros recém-nascidos e aumentou com o avançar da idade. Os neutrófilos dos bezerros Limousin apresentaram maior capacidade de redução do NBT do que os dos bezerros Nelore, notadamente após o segundo mês de vida. Essa diferença não provocou reflexos sobre a saúde dos animais e pode ser resultado da infecção natural e assintomática com o Anaplasma marginale.

The relationship of pancreatic exocrine function with the staging and the size of tumor in the patients with pancreatic cancer / 中华胰腺病杂志

Objective To investigate the relationship of pancreatic exocrine function with the pancreatic cancer staging and the size of tumor. Methods N-benzoyl-tryrosyl para-aminobenzoic acid (NBT- PABA) test was used to measure the pancreatic exocrine function of 39 pancreatic cancer patients, 46 chronic pancreatitis patients and 20 normal subjects. In pancreatic cancer group, the relationship of pancreatic exocrine function with the size of tumor (TS) and JPS classification (T factor) was analysed. Results The rate of NBT-PABA excretion in normal subjects, chronic pancreatitis patients were (78.9±15.9)%, (58.6± 19.3)%, respectively; in mild, moderate, severe chronic pancreatitis patients, the values of NBT-PABA were (75.5±23.6)%, (57.9±21.5)%, (45.5±16.7)% ; respectively. The rate of NBT-PABA excretion in pancreatic cancer patients was (47.6±18.3)%, and the rate of NBT-PABA excretion in patients with T3+T4 stage was (42.2±21.70%, and was obviously less than (64.8±11.2)% of T1+T2 stage (P<0.05). Tthe rate of NBT-PABA excretion in patients with TS3+TS4 was (34.8±17.2)%, and was significantly lower than (55.6±23.5)% of TS1+TS2(P<0.05). The rate of NBT-PABA excretion in patients with pancreatic head cancer was (42.5±16.4)%, which was significantly lower than (71.8±9.6)% of the pancreatic body and tail (P<0.05). In the 33 patients with pancreatic head cancer, the rate of NBT-PABA excretion in patients with main pancreatic duct stricture was (54.2±14.1) %, which was significantly higher than (37.6± 14.1)% of patients with main pancreatic duct interruption (P<0.05). There was no significant difference in pancreatic exocrine function between pancreatic cancer and moderate or severe chronic pancreatitis.Conclusions The pancreatic exocrine function was related to the pancreatic cancer staging and the size of tumor to some degree,but it was affected by mass location,and it was also affected by degrees of the pancreatic duct obstruction. The pancreatic exocrine function can not be used to differentiate pancreatic cancer from moderate or severe chronic pancreatitis.

Comparison between immunological markers in cord blood of preterm and term babies in Hospital USM

A cross sectional pilot study using convenient sampling method was conducted to evaluate various immunological parameters in preterm babies and term babies. Cord blood from 36 preterm and 36 term babies was taken and the following parameters were determined: Immunoglobulin G, A and M, Complement 3 and 4 and NBT. The results showed that NBT was significantly reduced in preterm babies compared to term babies (7.5% versus 12.0%; p= 0.001). The complement levels, C3 (0.5114 versus 0.7192 g/l; p<0.001) and C4 (0.07 versus 0.14g/l; p<0.001) were significantly lower in preterm babies than in the term babies. The mean IgG level in preterm babies was significantly lower than in term babies (9.5583 versus 14.2806 g/l, p<0.001). IgM (0.1 versus 0.2g/l; p<0.001) and IgA (0.210 versus 0.225g/l; p=0.036l) levels were significantly lower in the preterm than in term babies. In conclusion, we found that NBT reduction, IgG, IgA, IgM, C3 and C4 levels were significantly lower in the preterm compared to term babies.

Effects of estrogen and progesterone on the proliferation and activity of osteoblastic cells / 대한치과교정학회지

Biomechanical reactions of tooth movement are the combination of bone formation and resorption, in which many paracrine factors are involved. The sex hormone is one of the paracrine factors and the sex hormonal level of an adult female varies according to the body condition, e.g. mensturation, pregnancy, postmenopause, etc. Although the exact mechanism is not clarified yet, estrogen and progesterone are known to regulate the function of osteoblast. Again osteoblast is reported to affect the function of osteoclast. The purpose of this study is to determine the influence of the female sex hormone, estrogen and progesterone, on the cell proliferation and activity of HOS and ROS17/2.8 cell line. The observed results were as follows. 1. Estrogen inhibited HOS cell proliferation and promoted ROS17/2.8 cell proliferation. 2. Estrogen increased the activity of alkaline phosphatase of HOS cell and reduced the activity of alkaline phosphatase of ROS17/2.8 cell. 3. Progesterone inhibited the proliferation of HOS and ROS17/2.8 cell, but had no influence on the activity of alkaline phosphatase. 4. Estrogen and progeterone did not have any particular effects on the activity of super oxide, nitric oxide and gelatinase of HOS and ROS17/2.8 cell.

Expression and characterization of the flavoprotein domain of gp91phox

Truncated forms of gp91(phox) were expressed in E. coli in which the N-terminal hydrophobic transmembrane region was replaced with a portion of the highly soluble bacterial protein thioredoxin (TRX). TRX-gp91(phox) (306-569), which contains the putative FAD and NADPH binding sites, showed NADPH-dependent NBT (nitroblue tetrazolium) reductase activity, whereas TRX-gp91(phox) (304-423) and TRX-gp91(phox) (424-569) were inactive. Activity saturated at about a 1:1 molar ratio of FAD to TRX-gp91(phox) (306- 569), and showed the same Km for NADPH as that for superoxide generating activity by the intact enzyme. Activity was not inhibited by superoxide dismutase, indicating that it was not mediated by superoxide, but was blocked by an inhibitor of the respiratory burst oxidase, diphenylene iodonium (DPI). In the presence of Rac1, the cytosolic regulatory protein p67(phox) stimulated the NBT reductase activity, but p47(phox) had no effect. Truncated p67(phox) containing the activation domain (residues 199- 210) stimulated activity approximately 2-fold, whereas forms mutated or lacking this region failed to stimulate the activity. Our data indicate that: 1) TRX-gp91(phox) (306-569) contains the binding sites for both pyridine and flavin nucleotides; 2) this flavoprotein domain shows NBT reductase activity; and 3) the flavin-binding domain of gp91(phox) is the target of regulation by the activation domain of p67(phox).

Clinical Study on Chronic Granulomatous Disease in Korea / 대한면역학회지

Chronic granulomatous disease (CGD) is one of congenital immunodeficient disease and a rare X-linked or autosomal recessive disease characterized by recurrent life- threatening infections and granuloma formation. We observed clinical features, laboratory findings and genetic subgroups of 33 children who were diagnosed with chronic granulomatous disease in the Department of Pediatrics, Seoul National University Children's Hospital. There were 23 males and 10 females. Activated NBT test of all patients revealed 0% positive cell and mothers of 15 patients had 25%- 75% normal neutrophils in the activated NBT test. According to the result of activated NBT test and family history, the ratio of X-linked and autosomal recessive inheritance was 2:3. There was a significant difference for the age at onset of the first infection in the different genetic subgroups. The X-linked group had the mean onset at 1.98 months of age and autosomal recessive group had a mean onset as late as 3.82 months (p<0.05). The most common type of the first infection was lymphadenopathies (41%) and other infections were skin pustules, fever, perianal abscess, pneumonia and chronic diarrhea. However, the age at diagnosis was not significant in the different genetic subgroups. Lymphadenitis (27%) was the most common infection, and pneumonia, gastrointestinal tract infection, skin infection were also common. The most common infectious agent was Candida sp. (5%) and other microorganisms involved were BCG, coagulase-negative staphylococcus, S. aureus, K/ebsiella pneumoniae, Aspergi/lus sp., and Enterococcus faecium. Chronic condition associated with CGD were hepatomegaly (59%), splenomegaly, and anemia of chronic disease, underweight, and lymphadenopathy. The leukocyte count of patients at diagnosis was within normal limit except in three patients and leukopenia was not observed in any of the patients. The humoral and cellular immunity and complement system were normal, but the level of Ig E in four patients was elevated. Early diagnosis of CGD can be made by suspicion if there are lymphadenitis after BCG vaccination and recurrent pyogenic infections under the first year of age. Though progression in the treatment of CGD, like gene therapy, is concerned, genetic counseling and prenatal diagnosis by carrier detection and molecular genetic analysis is thought to be necessary.

A case of chronic granulomatous disease

No abstract available.