SUMMARYTo continue the search for immunological roles of breast milk, cDNA microarray analysis on cytokines and growth factors was performed for human milk cells. Among the 240 cytokine-related genes, osteopontin (OPN) gene ranked top of the expression. Real-time PCR revealed that the OPN mRNA levels in colostrum cells were approximately 100 times higher than those in PHA-stimulated peripheral blood mononuclear cells (PBMNCs), and 10 000 times higher than those in PB CD14+ cells. The median levels of OPN mRNA in early milk or mature milk cells were more than three times higher than those in colostrum cells. Western blot analysis of human milk showed appreciable expression of full-length and short form proteins of OPN. The concentrations of full-length OPN in early milk or mature milk whey continued to be higher than those in colostrum whey and plasma as assessed by ELISA. The early milk (3-7 days postpartum) contained the highest concentrations of OPN protein, while the late mature milk cells (1 years postpartum) had the highest expression of OPN mRNA of all the lactating periods. The results of immunohistochemical and immunocytochemical staining indicated that OPN-producing epithelial cells and macrophages are found in actively lactating mammary glands. These results suggest that the persistently and extraordinarily high expression of OPN in human milk cells plays a potential role in the immunological development of breast-fed infants.

Transient thrombocytosis is commonly observed in preterm infants after birth, but its physiological mechanism is still unknown. To understand the mechanism of the transient thrombocytosis in preterm infants we firstly evaluated a correlation between platelet counts and thrombopoietin (TPO) levels in preterm infants and next c-mpl mRNA levels on platelets in healthy preterm infants longitudinally during a half-year of life. The mean platelet counts in 45 very low birth weight infants (mean gestational age 27.4+/-1.8 weeks, mean birth weight 1047+/-249 g) was 230+/-71x10(9)/l just after birth and thereafter gradually increased to 579+/-178x10(9)/l by 5 weeks of age. The platelet counts continued this level for about next 8 weeks. Serum TPO levels soon after birth and at 1 month of age were significantly higher than those at the age of 2-6 months. There was a significant negative correlation between platelet counts and serum TPO values. The c-mpl expression levels on platelets at birth and at 1 month of age tended to be lower than those on platelets from adults, and the c-mpl levels gradually increased through 6 months of age, although they were still lower than those of adults. Our results suggest that low expression of TPO receptor on platelets until 1 month after birth cause a decreased TPO clearance and keep a high level of free TPO in blood, thereby promoting platelet production from megakaryocytes or their progenitors in bone marrow, resulting in the subsequent thrombocytosis in preterm infants.

The mean age was 28.4 7.6 (mean SEM) days at the time of the erythrocyte concentrate transfusions. The volume of the erythrocyte concentrate transfusion was 15±20 ml/kg body weight. The mean haemoglobin before transfusion was 5.9 0.3 mmol/l (9.5 0.48 g/dl), mean haematocrit was 0.26 0.17%. After transfusion the mean haemoglobin increased to 8.7 1.0 mmol/l (14.0 1.61 g/dl) and the haematocrit rose to 0.43 0.5% (P £ 0.05). The mean caloric intake of the ®ve analysed children within the period from 3 days before and 3 days after erythrocyte concentrate transfusion was 118 21 kcal/kg body weight. None of the transfusions was given within less than 1 week after steroid and/or antibiotic treatment and none of the ®ve infants was ventilated during the observation period.Longitudinal growth as assessed by mini-knemometry increased from 0.22 mm/day before transfusion to 0.43 mm/day after transfusion (P £ 0.02) (Fig. 2).The lower leg length growth rate 48 h before erythrocyte concentrate transfusion was signi®cantly less than the growth rate of the anaemic children averaged over all time points (0.38 mm/ day). Most importantly, after transfusions the growth rate exceeded the overall mean growth rate of the ®ve premature infants and was signi®cantly higher than before the transfusions.The present investigation indicates that a single transfusion of erythrocyte concentrate can signi®cantly stimulate short-term growth. For ethical reasons, no additional blood sampling for endocrine investigations was performed. Thus, it is unclear whether or not blood transfusions enhance longitudinal growth via endocrine mechanisms, possibly due to growth factors present in the transfused blood. Alternatively, bone growth could directly be stimulated by improved oxygen transport capacity after erythrocyte concentrate transfusion. References1. Gibson AT, Pearse RG, Wales JKH (1993) Knemometry and the assessment of growth in premature babies. Arch Dis Child 69:498±504 2. Hermanussen M (1998) The analysis of short-term growth. Horm Res 49:53±64 3. Hermanussen M, Seele K (1997) Mini-knemometry: an accurate technique for lower leg length measurements in early childhood. Ann Hum Biol 24:307±313 4. Kaempf DE, P¯uÈ gler MS, Thiele AM, Hermanussen M, Linderkamp O (1998) In¯uence of nutrition on growth in premature infants: assessment by knemometry. Ann Hum Biol 25:127±136 5. Michaelsen KF, Skov L, Badsberg JH, Jorgensen M (1991) Short-term measurement of linear growth in preterm infants: validation of a hand-held knemometer. Pediatr Res 30:464±468Sir: We report a streptococcal brain abscess in chronic granulomatous disease (CGD), and discuss the pathogenicity of the bacteria as poor producers of hydrogen peroxide. A 20-year-old male with X-linked CGD was hospitalized because of headaches. CGD had been diagnosed at 7 years of age, based upon undetectable superoxide production and lack of gp91phox expression [4]. He had pituitary dwar®sm (height:131 cm, weight:26 kg), and liver abscess-induced hypersplenism, but no other immunode®ciencies. Body tempera...

ObjectiveNeonatal-onset mitochondrial disease has not been fully characterised owing to its heterogeneity. We analysed neonatal-onset mitochondrial disease in Japan to clarify its clinical features, molecular diagnosis and prognosis.DesignRetrospective observational study from January 2004 to March 2020.SettingPopulation based.PatientsPatients (281) with neonatal-onset mitochondrial disease diagnosed by biochemical and genetic approaches.InterventionsNone.Main outcome measuresDisease types, initial symptoms, biochemical findings, molecular diagnosis and prognosis.ResultsOf the 281 patients, multisystem mitochondrial disease was found in 194, Leigh syndrome in 26, cardiomyopathy in 38 and hepatopathy in 23 patients. Of the 321 initial symptoms, 236 occurred within 2 days of birth. Using biochemical approaches, 182 patients were diagnosed by mitochondrial respiratory chain enzyme activity rate and 89 by oxygen consumption rate. The remaining 10 patients were diagnosed using a genetic approach. Genetic analysis revealed 69 patients had nuclear DNA variants in 36 genes, 11 of 15 patients had mitochondrial DNA variants in five genes and four patients had single large deletion. The Cox proportional hazards regression analysis showed the effects of Leigh syndrome (HR=0.15, 95% CI 0.04 to 0.63, p=0.010) and molecular diagnosis (HR=1.87, 95% CI 1.18 to 2.96, p=0.008) on survival.ConclusionsNeonatal-onset mitochondrial disease has a heterogenous aetiology. The number of diagnoses can be increased, and clarity regarding prognosis can be achieved by comprehensive biochemical and molecular analyses using appropriate tissue samples.

No abstract