Akemi Yamamoto

Increased serum nitrate levels in infants with atopic dermatitis

Background: The pathogenesis of atopic dermatitis (AD) is still unknown. A recent study has shown that inducible nitric oxide synthase (iNOS) is expressed in the atopic skin lesion, suggesting the involvement of nitric oxide in the skin inflammation of AD. The purpose of the study was to examine serum nitrate (NO3) levels in relation to the disease severity in children with AD.

Role of reactive oxygen species in neutrophil apoptosis following ingestion of heat‐killed Staphylococcus aureus

Neutrophils, short‐lived leucocytes that die by apoptosis, play an important role in the first stage of defense against bacterial infections. It has been reported that phagocytosis of intact bacteria or Candida albicans can accelerate neutrophil apoptosis. However, the mechanism of phagocytosis‐mediated neutrophil apoptosis is not well characterized. In this study, we evaluated whether ingestion of heat‐killed Staphylococcus aureus (S. aureus) enhances neutrophil apoptosis and whether this type of apoptosis is mediated by oxidative stress by using antioxidants and polymorphonuclear leucocytes (PMNs) from patients with chronic granulomatous disease (CGD). Co‐culture of PMNs with varying doses of S. aureus resulted in accelerated PMN death in a dose‐ and time‐dependent manner. Increased PMN apoptosis was observed by both Annexin V and PI staining. Similar results were observed in PMNs of CGD patients. Dimethyl sulphoxide (DMSO, an OH• scavenger) did not significantly inhibit either S. aureus‐ingested PMN apoptosis or spontaneous PMN apoptosis. On the other hand glutathione (GSH, an H2O2 scavenger) significantly inhibited both types of apoptosis.

Serum eosinophil derived neurotoxin may reflect more strongly disease severity in childhood atopic dermatitis than eosinophil cationic protein

Serum levels of eosinophil cationic protein (ECP) have been shown to be a good parameter of the disease severity of patients with atopic dermatitis (AD). However, the relationship between the disease severity and the eosinophil derived neurotoxin (EDN) has not been established in AD patients. The purpose of this study is to examine serum ECP and EDN levels in relation to the disease severity in AD children. Serum ECP and EDN levels were assessed in relation to the skin scores in 34 AD children (18 boys and 16 girls; age 0.6 to 7years: mean+/-S.D. 2.2+/-1.9) and six non-atopic control children (three boys and three girls; age 1 to 3years: mean+/-S.D. 1.7+/-0.9). Serum ECP and EDN levels of the patients with AD were significantly increased compared with the non-atopic controls. Serum EDN levels of the patients were also related to the disease severity. The skin scores were more significantly correlated with serum EDN levels than ECP levels. We concluded that serum EDN may reflect more strongly disease severity as eosinophilic activation in AD children than serum ECP.

Increased nitric oxide production by neutrophils from patients with chronic granulomatous disease on trimethoprim–sulfamethoxazole

Chronic granulomatous disease (CGD) is an inherited disease characterized by severe and recurrent bacterial and fungal infections. Phagocytic cells of CGD patients are unable to produce superoxide anion, and their efficiency in bacterial killing is significantly impaired. In these patients, the prophylactic and therapeutic validity of a long-term use of trimethoprim-sulfamethoxazole (TMP-SMX) has been well established. However a role of nitric oxide (NO) produced by phagocytic cells from CGD patients is unknown, and the mechanism of TMP-SMX in CGD is unclear. We have directly measured NO production in whole human blood by using 4,5-diaminofluorescein as a novel fluorescent indicator for intracellular NO. Intracellular NO production of gated neutrophils increased time dependently when stimulated by lipopolysaccharide (LPS) and calcium ionophore. Although all polymorphonuclear leukocyte (PMN) specimens from patients with CGD failed to generate hydrogen peroxide, NO production by CGD PMNs was significantly increased compared with that of control PMNs (p<0.05). TMP-SMX with LPS significantly increased compared with LPS-stimulated samples at clinical (n=5, p<0.05) and 10-fold clinical concentrations (n=5, p<0.01). TMP-SMX with LPS in CGD PMNs significantly increased the production of NO in comparison with the LPS stimulation at 10-fold clinical concentrations (n=5, p<0.05). In conclusion, our data indicate the possibility that NO production by neutrophils from patients with CGD treated with TMP-SMX has a role of bactericidal activity instead of O(2)(-) in host defense mechanism.

Dizygotic twin sisters with myelokathexis: Mechanism of its neutropenia

Dizygotic twin sisters were first found to have neutropenia at 1 year of age when evaluated for recurrent pulmonary infections. Since then they have remained neutropenic (0.05∼0.5 × 109/l). Despite of their neutropenia, myeloid hyperplasia was evident on a marrow smear examination, and a number of cells were hypersegmented with fine interlobular bridging with chromatin strands and cytoplasmic vacuolation. Electron microscopy showed apoptotic cells with condensed nuclei and apoptotic bodies in the cytoplasm. Although life span, hydrogen peroxide production, phagocytosis, spreading, and chemotaxis of peripheral neutrophils were normal, the survival of bone marrow neutrophils in both infants was markedly decreased when compared with that of normal bone marrow neutrophils. During the bone marrow culture apoptotic neutrophils were observed at an earlier stage in both patients than in normal controls, biochemically and morphologically. Morphology of bone marrow neutrophils in both patients resembled that of cultured control bone marrow neutrophils. Peripheral neutropenia and appearance of characteristic neutrophils in the bone marrow in myelokathexis are considered to be an expression of apoptosis of bone marrow neutrophils. Am. J. Hematol. 62:106–111, 1999.

Two cases of autoimmune neutropenia possibly induced by β-lactam antibiotics in infants

This report describes two infants who had neutropenia develop after treatment with &bgr;-lactam antibiotics. The first patient, a 9-month-old girl, was administered flomoxef (FMOX); the second patient, a 14-month-old boy, was administered cefotiam (CTM). Both infants were found to have neutropenia 4 to 5 days after they were placed on respective antibiotics, and neutropenia had persisted despite antibiotics withdrawal for 1 to 3 months. Drug-induced lymphocyte stimulation test (DLST), granulocyte-bound antibodies, serum granulocyte antibodies, and immunoblotting analysis indicated that &bgr;-lactam antibiotics possibly triggered production of granulocyte autoantibody with resultant autoimmune neutropenia.

Ultrasonographic follow-up of the healing process of medically treated hypertrophic pyloric stenosis

Abstract In hypertrophic pyloric stenosis (HPS), prompt pyloromyotomy is, in general, the treatment of choice. There has been no information available as to the natural history of the pyloric tumour. We present four infants with medically treated HPS who were followed by sonography to observe the anatomical changes that occur with atropine sulfate. The initial change was shortening of the pyloric canal, followed by thinning of the muscular layer as clinical symptoms improved.

Heterogeneity in F-actin polymerization of cord blood polymorphonuclear leukocytes stimulated by N-formyl-methionyl-leucyl-phenylalanine.

Abstract Background: To elucidate the mechanism responsible for defects of polymorphonuclear leukocyte (PMNL) chemotaxis of neonates, we determined actin polymerization of NBD (7‐nitrobenz‐2‐oxa‐diazol)‐phallacidin‐stained PMNL following stimulation with either N‐formyl‐methionyl‐leucyl‐phenylalanine (fMLP) or phorbol myristate acetate (PMA) in cord blood and adult controls.

FcγRIII b and FcγRIIa polymorphism may affect the production of specific NA1 autoantibody and clinical course of autoimmune neutropenia of infancy

Abstract We studied 18 children with autoimmune neutropenia (AIN) to evaluate whether there was a possible relationship between the specificity of granulocyte autoantibodies (anti-NA1,2) and the phenotype of the NA system. Direct granulocyte immunofluorescence test (D-GIFT) was positive in all patients, and indirect granulocyte immunofluorescence test (I-GIFT) was positive in 17 of these 18 patients, respectively. Fourteen of 18 patients showed preferential binding to neutrophils from NA(1+2−) phenotyped donors. Immunoblotting with anti-FcγRIIImAb showed that IgG prepared from 7 of 12 patients precipitated both FcγRIIIb from NA1 and NA2 neutrophil lysate, whereas the other 5 precipitated only NA1. Patients’ IgG did not react with purified FcγRIIa. FcγRIIIb genotype were NA(1+2−) in 15 of 18 patients and NA(1+2+) in the other 3. FcγRIIa type of all patients were (H+R−). These distributions were significantly different from those of healthy Japanese blood donors ( n = 608). The genotype of FcγRIIIb and FcγRIIa may affect the production of neutrophil specific auto-antibodies in AIN of infancy and influence its clinical course.

Dental Infections as a Cause of Persistent Fever in a Patient with Chronic Granulomatous Disease

Chronic granulomatous disease (CGD) is a genetically determined primary immunodeficiency disease in which phagocytic cells are unable to kill certain ingested bacteria and fungi.1 The disease is characterized by recurrent or persistent infections, but dental infections have rarely been reported.2 We describe a male patient with Xlinked CGD who suffered from chronic apical periodontitis and persistent fever for more than 50 days’ duration with no complaint of dental pain. Patient Report