Hideomi Asanuma

Role of Milk Whey in the Transmission of Human Cytomegalovirus Infection by Breast Milk

Breast‐fed infants are susceptible to human cytomegalovirus (HCMV) infection via breast milk. In our previous study, HCMV was isolated more frequently from breast milk at later than one month after delivery than from colostrum or early breast milk. To clarify the role of milk cells and whey in vertical infection by breast feeding, we separated breast milk into milk cells and whey and examined each fraction for the presence of HCMV. We collected breast milk from mothers who breast‐fed their infants (aged from 3 days to 2 months). The breast milk was centrifuged and separated into the middle layer (layer of milk whey) and the pellet (containing milk cells). We attempted to isolate HCMV from whey and to detect HCMV immediate early (IE) DNA in both milk whey and cells. HCMV was isolated from 7 out of 35 (20.0%) whey samples and HCMV IE DNA was detected from 15 out of 35 (42.9%) whey and/or milk cells. Detection rates of HCMV IE DNA in the whey layer and milk cells were 39.1% (25 out of 64) and 17.2% (11 out of 64), respectively. HCMV IE DNA was not detected in colostrum, but was detected in breast milk samples one month after delivery. Therefore, cell‐free HCMV shed into milk whey may have a more important role in vertical infection by breast milk than cell‐associated HCMV in the milk.

Chlamydia trachomatis infection in early neonatal period

BackgroundThe clinical characteristics of Chlamydia trachomatis respiratory tract infections in Japanese neonates were investigated.MethodsClinical, laboratory and microbiological characteristics of five infants with pneumonia due to C. trachomatis in early neonatal period were analyzed.ResultsOnly C. trachomatis was identified in 4 infants. Both C. trachomatis and cytomegalovirus was identified in one. Wheezing, tachypnea and cyanosis were common in infants. Mothers of five infants had negative chlamydial EIAs at 20 weeks of gestation.ConclusionsWe identified five cases of C. trachomatis respiratory tract infections in early neonatal period with the possibility of intrauterine infection. Targeted screening, early diagnosis, and effective treatment of perinatal and neonatal chlamydial infections seems to be necessary

Brain tumors associated with infantile spasms

Two patients with brain tumors associated with infantile spasms are reported. Both infants displayed typical clinical features of infantile spasms, comprising tonic spasms manifesting in series and hypsarrythmia. In Patient 1, magnetic resonance imaging revealed a tumor in the hypothalamic region, suggestive of hypothalamic hamartoma. In Patient 2, cranial computed tomography and magnetic resonance imaging indicated the existence of a primary brain tumor with calcification in the right temporal lobe. Adrenocorticotropic hormone therapy combined with clonazepam relieved seizures in both infants. In Patient 1, resection of the hypothalamic tumor is impossible because the tumor lacks a stalk. In Patient 2, pathologic investigation of removed tumor tissue demonstrated mixed-oligoastrocytoma. It is suggested that focal lesions, like those in our patients, are involved in the development of infantile spasms.

Transmission of cytomegalovirus

the specific, time-sensitive exposures that might contribute to adult disease. Undernutrition could be one such exposure, but the timing and specifics should be more clearly defined. Prenatal exposures related to stress hormones, toxins, or oxygen transport also could participate, and genetic contributions cannot be excluded. Even if we do not identify the causal exposures, we may still derive benefits from interpreting fetal characteristics that persist into later life. Persisting characteristics might help us find the people who require special assistance or interventions.

Analysis of human cytomegalovirus-infected peripheral blood mononuclear cells from infants with liver dysfunction by flow cytometry and the polymerase chain reaction

Perinatal human cytomegalovirus (HCMV) infection often involves the hepatobiliary tract, but infected individuals usually remain asymptomatic. We investigated the role of CD8+ lymphocytes in 13 infants with liver dysfunction associated with perinatal HCMV infection. In three patients more than 40% of CD8+ cells were positive for HCMV immediate early antigen (IEA) and late antigen (LA) by flow cytometry after selection of T lymphocytes subpopulations. In the other 10 infants, 20% to 30% of CD8+ cells were positive for HCMV IE A and LA. HCMV IE DNA was detected in CD8+ cells from one infant, in CD4+ cells from one infant, and in both CD4+ and CD8+ cells from three infants. HCMV infection of CD8+ cells may play an important role in the process of perinatal primary infection. J. Leukoc. Biol. 56: 187–191; 1994.

Detection of cytokines and cytomegalovirus DNA in serum as test for congenital infection

Maternal serum samples at 10 and 22 weeks of gestational age and cord blood samples were available from six cases of asymptomatic congenital human cytomegalovirus (HCMV) infection. Meaningful rises of serum IgG-antibody titers by ELISA occurred in three cases. Serum interferon (IFN)-gamma activity was detected in all six cases. Serum cell free soluble interleukin-2 receptor (sIL-2R) activity rose above the normal range (145-519 U/ml) in one IgG and IgM antibody-positive and three IgG antibody-positive woman. Serum levels of sIL-2R and IFN-gamma were not elevated in anti-HCMV antibody-negative healthy pregnant women. No HCMV IE DNA was detected by PCR in the serum of any of the pregnant women. HCMV DNA was detected in the serum of one of six infants with asymptomatic congenital HCMV infection. Assessment of the changes of serum cytokines such as sIL-2R and IFN-gamma in HCMV antibody-positive pregnant women may be useful for the prenatal diagnosis of active HCMV infection during pregnancy.

Ictal Video-EEG Analysis of Infantile Neuroaxonal Dystrophy

Summary: A 4‐year‐old boy with infantile neuroaxonal dystrophy (INAD) showed gradual deterioration from age 9 months with seizure development at age∼36 months. Sural nerve biopsy performed at age 42 months confirmed INAD. The seizure, recorded by video‐EEG, consisted of a series of symmetrical tonic spasms of both upper extremities after a prodrome period of staring and akinesis. Each spasm had phonation, and episodic autonomic symptoms such as hypertension and flushing of the face occurred throughout the seizure. Ictal EEG with each tonic spasm, showed diffuse 1‐s, irregular sharp and highvoltage slow wave complexes followed by desynchronization.

Latent infection and reactivation of human cytomegalovirus

Abstract Human cytomegalovirus (HCMV) is the most common cause of congenital and perinatal infections throughout the world. Primary infection with HCMV usually follows a benign course, but the virus remains latent or persistent in the host cell thereafter. Under immunosuppressive conditions, latent or persistent infection can be reactivated to produce a wide variety of clinical manifestations. Understanding the epidemiology of HCMV infection is a key element in development of strategies for prevention of infection. Definition of sites and mechanisms involved in the maintenance of latent or persistent HCMV infection and reactivation is also essential for a thorough understanding of the pathogenesis of HCMV infection. This mini review focuses on recent advances in the study of persistent infection and reactivation of HCMV. Although the actual sites of latency or persistence of HCMV infections are still controversial, peripheral blood mononuclear cells (PBMC) and endothelial cells appear to be the principal site of infection. Persistent infections caused by HCMV could be augmented by a decrease in major histocompatibility complex (MHC) expression as well as by virus-mediated immune dysfunction. It is also likely that specific cellular interactions as well as production of several cytokines are necessary for the reactivation of HCMV.

Human cytomegalovirus infection during pregnancy and detection of specific T cells by intracellular cytokine staining

OBJECTIVE The flow cytometric assay was evaluated as a tool for real-time monitoring of human cytomegalovirus (HCMV)-specific cellular immunity in pregnant women. METHODS We screened for HCMV infection in pregnant women in Sapporo, Japan, during the year 2000, by serologic assays, virus isolation from urine, and PCR to detect DNA in cervical swabs. The frequencies of HCMV-specific CD4+ T cells in pregnant women with serum anti-HCMV IgG antibody were detected by intracellular cytokine (ICC), interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) staining. RESULTS The levels of intracellular cytokines in pregnant women with serum anti-HCMV IgG antibody were significantly higher than those in women without anti-HCMV IgG antibody (P = 0.011 for IFN-gamma and P = 0.023 for TNF-alpha) but lower than those in non-pregnant women with serum anti-HCMV IgG antibody. Frequencies of HCMV-specific CD4+ T cells were higher in infants with symptomatic congenital infection than in infants with asymptomatic perinatal infection. CONCLUSIONS This ICC assay may reflect immunologic activity against HCMV infection in pregnant women with immunosuppressive conditions.

Infantile neuroaxonal dystrophy: Axonal changes in biopsied muscle tissue

Dystrophic axons were found in the biopsied muscle tissue of a 17-month-old hypotonic infant after confirmation of a diagnosis of infantile neuroaxonal dystrophy (INAD) by subsequent peripheral nerve biopsy. He manifested gradual deterioration and had brief tonic seizures. The sural nerve biopsy, performed at age 42 months, confirmed INAD. Intensive ultrastructural investigation of the preceding muscle biopsy specimens demonstrated infrequent but definite findings of axonal degeneration in the musculature. Ultrastructural investigation of muscle biopsy should include a careful search for neural tissue because in INAD axonal changes occur primarily in the presynaptic region.