Both Granulocytic and Non-Granulocytic Blood Cells Are Affected in Patients with Severe Congenital Neutropenia and Their Non-Neutropenic Family Members: An Evaluation of Morphology, Function, and Cell Death.

Objective: To examine granulocytic and non-granulocytic cells in children with severe congenital neutropenia (SCN) and their non-neutropenic parents.

Materials And Methods: Fifteen patients with SCN and 21 non-neutropenic parents were evaluated for a) CD95, CD95 ligand, annexin V, propidium iodide, cell cycle, and lymphocyte subsets by flow cytometry; b) rapid cell senescence (of leukocytes) by senescence-associated β-galactosidase stain; c) aggregation tests by aggregometer; d) in vitro bleeding time by PFA-100 instrument; e) mepacrine-labeled dense granule number of thrombocytes by fluorescence microscope; and f) hematomorphology by light and electron microscope. HAX1, ELANE, G6PC3, CSF3R, and JAGN1 mutations associated with SCN were studied in patients and several parents.

The first report of a homozygous codons 9/10 (+T) β-thalassemia mutation in a Turkish patient.

For the first time in Turkey, we report a thalassemic patient with a homozygous codons 9/10 (+T) genotype. Currently, the patient is 3 years and 2 months old and received an initial transfusion at the age of 18 months. After being alloimmunized following this transfusion, he required frequent transfusions, every week to every other week.

Cytotoxic effects of etephon and maleic hydrazide in Vero, Hep2, HepG2 cells.

The toxicity of etephon and maleic hydrazide, used as plant growth regulators in agriculture, were reported as low in mammals in previous studies. However, in vitro cytotoxicity studies in mammalian cells are currently missing to understand their toxicity at molecular level. In the current study, the cytotoxicity of these compounds, were studied in Vero (African green monkey kidney epithelium), HepG2 (human hepatocellular carcinoma), Hep2 (human epidermoid cancer) cells by MTT ((3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetrazolium bromure) and LDH (lactate dehydrogenase) assays.

Recurrent macrophage activation syndrome associated with heterozygous perforin W374X gene mutation in a child with systemic juvenile idiopathic arthritis.

Background: Recurrent macrophage activation syndrome (MAS) is rarely reported.

Aim: To describe recurrent MAS in a 2.5-year-old girl with systemic juvenile idiopathic arthritis and heterozygous perforin mutation, which may have a role in the patient's first recurrence despite use of the HLH-2004 treatment protocol.

The frequency of A91V in the perforin gene and the effect of tumor necrosis factor-α promoter polymorphism on acquired hemophagocytic lymphohistiocytosis.

Objective: Numerous acquired etiological factors, such as infections, malignancies, and collagen tissue disorders, are involved in the development of acquired hemophagocytic lymphohistiocytosis (AHLH). Not everyone with the same etiological factors developments AHLH, which suggests the role of additional genetic or environmental predisposing factors that remain to be identified.

Methods: Perforin gene A91V missense transition (C>T change at position 272 in exon 2 of the perforin gene) and TNF-α gene promoter-1031 T>C nucleotide substitution are 2 candidate genetic predisposing factors due to their potential to alter inflammatory responses.

Smaller hippocampus volume is associated with short variant of 5-HTTLPR polymorphism in medication-free major depressive disorder patients.

Aim: Serotonin is known for its importance in the pathophysiology of major depressive disorder. Although the hippocampus is one of the key regions in which neurogenesis occurs, and serotonin plays an important role in neurogenesis, results of studies that investigate effect of the 5-HTTLPR polymorphism on hippocampal volumes in major depressive disorder are inconclusive.

Method: We looked for a relationship between the 5-HTTLPR polymorphism and hippocampal volumes in 44 depressed patients (mean age ± SD 33.

Plasminogen activator inhibitor I 4G/5G polymorphism in neonatal respiratory distress syndrome.

Fibrin monomers inhibit surfactant function. 4G/5G insertion/deletion polymorphism plays an important role in the regulation of plasminogen activator inhibitor 1 (PAI-1) gene expression. To examine the genotype distribution of PAI-1 polymorphism in 60 infants with respiratory distress syndrome (RDS) and 53 controls, an allele-specific polymerase chain reaction (PCR) was used.

Assessment of clinical and laboratory presentations of familial hemophagocytic lymphohistiocytosis patients with homozygous W374X mutation.

Homozygous W374X mutation was identified in unrelated 13 patients (6M/7F) from consanguineous families, 62% of which had history of deceased sibling. Haplotype analysis provided evidence for the probable existence of a founder effect. Age at disease onset ranged from 1 day to 5.

ALX4 dysfunction disrupts craniofacial and epidermal development.

Genetic control of craniofacial morphogenesis requires a complex interaction of numerous genes encoding factors essential for patterning and differentiation. We present two Turkish families with a new autosomal recessive frontofacial dysostosis syndrome characterized by total alopecia, a large skull defect, coronal craniosynostosis, hypertelorism, severely depressed nasal bridge and ridge, bifid nasal tip, hypogonadism, callosal body agenesis and mental retardation. Using homozygosity mapping, we mapped the entity to chromosome 11p11.

Excessive naked megakaryocyte nuclei in myelodysplastic syndrome mimicking idiopathic thrombocytopenic purpura: a complicated pre- and post-transplantation course.

A boy 3 years 7 months old with thrombocytopenia and history of intracranial hemorrhage who underwent bone marrow transplantation is presented. He was refractory to steroids, immunoglobulin G, vincristine, azathioprine, cyclosporine A, interleukin-11, chemotherapy, and splenectomy. Idiopathic thrombocytopenic purpura was excluded by light /electron microscopic and flow cytometric findings; the diagnosis of refractory cytopenia, a subgroup of pediatric myelodysplastic syndrome, was made.

The effect of depression, BDNF gene val66met polymorphism and gender on serum BDNF levels.

Objective: To determine the effect of BDNF gene val66met polymorphism on serum BDNF levels in drug-free patients with major depressive disorder (MDD) and healthy subjects, that differ by gender.

Methods: Sixty-six drug-free patients (19 males+47 females) with non-psychotic MDD and fifty-six healthy controls (18 males+38 females) were recruited. Three-way ANOVA was employed to analyze the effect of mental health status, met-carriage and gender on Hamilton Depression Rating Scale (HDRS) scores and serum BDNF levels, by using the MIXED Procedure (SAS).

Transient depletion of innate immunity in varicella infections in otherwise healthy children.

Objective: Varicella is a common childhood infection and has a number of complications in the unvaccinated population. Perforin, found in natural killer cells, is important for the killing of virally infected cells. For this reason, the aim of this study was to determine natural killer cell count and activity, perforin expression, and Fas and soluble Fas ligand (sFas-L) levels in immunocompetent children with varicella infection and define any possible relations between the levels and varicella complications.

Neonatal primary hemophagocytic lymphohistiocytosis in Turkish children.

Although the data on hemophagocytic lymphohistiocytosis (HLH) has gradually increased, the neonatal-onset HLH patients have usually been reported as case reports or together with other age groups of patients. The aim of this study was to draw attention to the clinical and laboratory characteristics of neonatal HLH cases. Herein, the data of 8 primary, neonatal-onset HLH patients are reported.

Placental fas/fas ligand expression in early pregnancy losses.

Problem: The aim of this study was to compare the expression levels of Fas and Fas ligand (FasL) in first-trimester placentas obtained from spontaneous abortions in patients with antiphospholipid antibody syndrome (APS) or factor V (FV) Leiden mutation, compared with values in placentas from induced abortions in patients negative for these conditions.

Method Of Study: We studied explants from 6- to 10-week-old placentas that had been prepared by collagenase digestion from 10 spontaneous abortions from APS-positive patients, nine spontaneous abortions in patients positive for FV Leiden mutation, and 10 induced abortions. All tissues were analyzed by flow cytometry for expression of Fas and FasL.

Clinical and molecular aspects of Turkish familial hemophagocytic lymphohistiocytosis patients with perforin mutations.

The aim of this study was to elucidate the pathologic sequence changes and associated clinical phenotypes in 9 new patients showing homozygosity for perforin gene among a total of 37 (24%) Turkish FHL families studied by linkage analysis. These 9 unrelated patients (5M/4F) were coming from consanguineous families and their presentation ages of systemic symptoms were ranged from birth to 15 years. Direct sequencing of coding exons of the perforin gene led to the identification of five different homozygous alterations.

Rapid cell senescence and apoptosis in lymphocytes and granulocytes and absence of GM-CSF receptor in congenital dysgranulopoietic neutropenia.

A girl with congenital dysgranulopoietic neutropenia (CDN) and her non-neutropenic mother with aphthae (A) were investigated. Apoptosis in lymphocytes and granulocytes of both patients (mother A+) were documented by high annexin and electron microscopic morphology. CD11b/CD18 of the daughter's granulocytes ranged between low to normal while that of the mother changed between very low to high levels through A(-) to A(+) periods.

Omeprazole inhibits natural killer cell functions.

This study was designed to determine the possible effects of omeprazole on human natural killer cells. Peripheral venous blood samples were taken from 20 peptic ulcer patients before and at the 14th and the 28th days of omeprazole treatment. Mononuclear cells were removed from blood and their capability of making conjugation with K562 target cells and lysing K562 target cells was evaluated.

Congenital dysgranulopoietic neutropenia.

We investigated a 15-year-old female with congenital dysgranulopoietic neutropenia (CDN) and her non-neutropenic mother who had recurrent stomatitis. In both patients, cells of the neutrophilic, eosinophilic, monocytic, megakaryocytic, and basophilic series were dysmorphic. Plasmacytoid lymphocytes and mild megaloblastic erythroid precursors were present.

Effect of short course high dose methylprednisolone on endothelin-1 and nitric oxide in children with acute lymphoblastic leukemia: a preliminary study.

We have investigated serum endothelin-1 (ET) and nitric oxide (NO) levels before and after a short course of high dose methylprednisolone (HDMP) in children with acute lymphoblastic leukemia (ALL) as an indicator of vasoconstrictor and vasodilator properties of endothelium. Nineteen children with ALL (aged 13-180 months; 5 girls and 14 boys) and 25 healthy children were included in the present study. The children with ALL were given HDMP (20 mg kg 1 day 1) alone for the first 5 days.

Prothrombin G20210A mutation in Turkish children with thrombosis and the frequency of prothrombin C20209T.

The prothrombin G20210A mutation has been described as the second most common genetic risk factor in thrombotic patients. Recently a new prothrombin gene variant namely prothrombin C20209T has also been found to be associated with thrombosis. In the present study the frequency of these two thrombin variants have been searched in two different groups.

Effects of prophylactic thyroid hormone replacement in euthyroid Hashimoto's thyroiditis.

Hashimoto's thyroiditis is the most frequent autoimmune thyroid disease. L-thyroxine therapy can reduce the incidence and alleviate the symptoms of this disease. The aim of this study was to evaluate the effects of prophylactic L-thyroxine treatment on clinical and laboratory findings of patients who were euthyroid at the time of diagnosis.

Lymphocyte subsets, TNF alpha and interleukin-4 levels in treated and untreated subacute sclerosing panencephalitis patients.

Immunologic studies in relation to clinical status might help to understand the pathogenesis of subacute sclerosing panencephalitis (SSPE) and the effect of treatment. We measured lymphocyte subsets and intracellular TNFalpha and interleukin-4 levels in peripheral blood in SSPE patients. Patients had elevated percentages of CD8+ cells compared to age-matched control children.

Neutrophil CD64 expression in Behçet's disease.

Objective: Hyperfunction of neutrophils is a characteristic finding in Behçet's disease (BD). Microbial agents have been proposed as causative agents in the disease flares. Fc gamma receptor 1 (CD64) is not normally expressed by neutrophils of healthy individuals, but is upregulated by these cells in response to microbial wall components and proinflammatory cytokines.

Levamisole: might it be used in treatment and prevention of atopic diseases?

As an antihelmintic and Th1-biased immunostimulant, levamisole has been used to restore impaired cell mediated immunity. We sought to explore whether the Th1 driving effect of levamisole may also have an influence on the course of allergic diseases, by shifting the Th2 dominant immunity more toward Th1-mediated response. BALB/c mice were sensitized intraperitoneally on days 0, 7, and 15 with ovalbumin (OVA).