Biomedical subjects

Ronit Gavrieli

Publications and source records attributed to Ronit Gavrieli.

5 recordsLinked to original sources

PubMed2005

Acute lymphoblastic leukemia in a patient with chronic granulomatous disease and a novel mutation in CYBB: first report.

We report for the first time a child with chronic granulomatous disease (CGD) who developed acute lymphoblastic leukemia (ALL). The diagnosis of CGD was made at the age of 4 months, by studies of his neutrophil functions. The superoxide production of the cells was negligible, as was the bactericidal activity. He was found to have a deficiency of the gp91(phox) subunit of the leukocyte NADPH oxidase, with the X-linked inheritance of the disease. DNA analysis revealed a C nucleotide insertion between C1028 and T1029. This insertion has not been described before and causes a frameshift and a premature stop codon at amino-acid position 347. The mother was found to be a carrier of this mutation. At the age of 16 months, the patient developed T-cell ALL. He was treated for 2 years, and today, 10 years since the diagnosis, he is disease-free. During the course of ALL and later, he suffered from recurrent severe pyogenic infections, but careful detection of the etiological agent and promptly instituted specific treatment resulted in his complete recovery. Although primary immune deficiencies have been reported to have an increased tendency to develop malignancies, until now there have been no reports of CGD patients with ALL.

Antineoplastic Agents↗

PubMed2005

Transient decrease of neutrophil chemotaxis following aerobic exercise.

PURPOSE: Intense exercise affects the immune system, increasing the susceptibility of athletes to viral and bacterial infections. We have previously shown a significant decrease of fMLP-neutrophil migration 24 h after aerobic exercise. In this study we aimed to look at the differential effect of different chemoattractants on neutrophil migration following aerobic exercise, to determine the recovery time, and to better understand the role of the cell skeleton behind the impaired chemotaxis. METHODS: Sixteen female volunteers aged 22-30 yr were tested before, 24, and 48 h after aerobic exercise (30 min running at 70% (.)VO(2max). The submaximal exercise test was conducted a week after the (.)VO(2max) test. We studied the membrane cell receptor response to fMLP, IL-8, and C5a, which have specific ligand-receptor pathways. Further, we studied the cytoskeletal response by investigating the cell polarization and the F-actin polymerization. RESULTS: Significant decrease of the neutrophil net chemotaxis was detected with fMLP, IL-8 and C5a, 24 h after exercise (50 +/- 5%, P = 0.0001; 48 +/- 12%, P = 0.0015; and 32 +/- 11%, P = 0.011, respectively). Complete recovery was observed within 48 h with all chemoattractants. Normal neutrophil random migration and F-actin polymerization were found. Decreased neutrophil polarization was detected (46 +/- 6% vs 22 +/- 8% of polarized cells, before and after effort, respectively; P = 0.004). Correlation between polarization and chemotactic migration was found (r = 0.945; P = 0.001). CONCLUSIONS: The impaired chemotactic response, observed 24 h after exercise, was similar using different chemoattractants. This finding indicates a possible exercise-induced effect on a common factor at the ligand-receptor level. The abnormal cell polarization indicates skeletal dysfunction that should be further investigated and elucidated. The normal fMLP-stimulated-F-actin polymerization reflects an adequate pathway of signal transduction for the formyl peptide.

Adult↗

PubMed2004

Unusual late presentation of X-linked chronic granulomatous disease in an adult female with a somatic mosaic for a novel mutation in CYBB.

Most patients with chronic granulomatous disease (CGD) have mutations in the X-linked CYBB gene that encodes gp91phox, a component of the phagocyte NADPH oxidase. The resulting X-linked form of CGD is usually manifested in boys. Rarely, X-CGD is encountered in female carriers with extreme expression of the mutated gene. Here, we report on a woman with a novel mutation in CYBB (CCG[90-92]-->GGT), predicting Tyr30Arg31-->stop, Val in gp91phox, who presented with clinical symptoms at the age of 66. The mutation was present in heterozygous form in genomic DNA from her leukocytes but was fully expressed in mRNA from these cells, indicating that in her leukocytes the X chromosome carrying the nonmutated CYBB allele had been inactivated. Indeed, only 0.4% to 2% of her neutrophils showed NADPH oxidase activity. This extreme skewing of her X-chromosome inactivation was not found in her cheek mucosal cells and is thus not due to a general defect in gene methylation on one X chromosome. Moreover, the CYBB mutation was not present in the DNA from her cheek cells and was barely detectable in the DNA from her memory T lymphocytes. Thus, this patient shows a somatic mosaic for the CYBB mutation, which probably originated during her lifetime in her bone marrow.

Aged↗

PubMed2004

Diurnal fluctuation of leukocyte G6PD activity. A possible explanation for the normal neutrophil bactericidal activity and the low incidence of pyogenic infections in patients with severe G6PD deficiency in Israel.

Acute hemolytic anemia associated with red blood cell (RBC) glucose-6-phosphate dehydrogenase (G6PD) deficiency is commonly encountered in the Mediterranean basin. Nevertheless, concomitant clinical evidence of white blood cell G6PD deficiency is extremely rare in Israel. This study sought to assess simultaneously levels of G6PD activity in polymorphonuclear leukocytes (PMN) and in red blood cells (RBC) of patients with G6PD deficiency, including full-term newborn infants. In PMN, the correlation between G6PD activity, hexose monophosphate shunt activity, and superoxide anion release was evaluated. In G6PD-deficient patients, a parallel and significantly decreased G6PD activity was found in neutrophils (range of activity 0-4.5 IU/10(6) PMN) and erythrocytes (range of activity 0-1.8 IU/g Hb), compared with healthy controls (5-23 IU/10(6) PMN and 2.4-6.4 IU/g Hb, respectively). A positive correlation was found in PMN between the levels of G6PD activity, hexose monophosphate (HMP) shunt activity, and superoxide anion release (p < 0.01). Nevertheless, all patients' bactericidal activity of neutrophils remained in the range of healthy controls. Although many episodes of acute hemolytic anemia were recorded, no increased incidence of pyogenic infections was observed in any group of patients investigated. Neutrophil and erythrocyte G6PD levels were re-assessed in some of these patients several times a day. A significant diurnal fluctuation of the enzyme activity was found. It is speculated that the patients produce fluctuating daily quantities of NADPH, sufficient to initiate the neutrophil respiratory burst and to achieve normal bactericidal activity, necessary to prevent the development of microbial infections.

Adolescent↗

PubMed2003

Overproduction of neutrophil radical oxygen species correlates with negative symptoms in schizophrenic patients: parallel studies on neutrophil chemotaxis, superoxide production and bactericidal activity.

Defective neutrophil function in schizophrenic patients has recently been reported. There are several lines of evidence to support the contribution of oxygen free radicals in schizophrenia, including increased lipid peroxidation, fatty acids and alterations in blood levels of anti-oxidant enzymes. Eighteen schizophrenic patients (DSM-IV) and 15 healthy controls were studied. Neutrophil chemotaxis, superoxide production and bactericidal activity were investigated. A statistically significant increase of superoxide anion release was found in schizophrenic patients compared with controls (mean+/-S.E.M., patients: 6.89+/-0.30 nmol O2-/10(6) cells/min, controls: 5.13+/-0.55 nmol O2-/10(6) cells/min). Moreover, a significant positive correlation between superoxide production and negative symptoms as assessed by the Positive and Negative Syndrome Scale was demonstrated. No differences were detected in chemotaxis and phagocytosis between schizophrenic patients and healthy controls. The present findings of a positive correlation between superoxide generation and negative symptoms in schizophrenic patients support the hypothesis that superoxide anion may participate in the pathogenesis of schizophrenia, as an excess of free radicals could contribute to the deterioration phase of the disease. Further studies are required to establish the role of oxidative stress in the ethiopathogenesis of schizophrenia.

Adult↗