Search

It has been reported that measles virus may be present in the intestine of patients with Crohn's disease. Additionally, a new syndrome has been reported in children with autism who exhibited developmental regression and gastrointestinal symptoms (autistic enterocolitis), in some cases soon after MMR vaccine. It is not known whether the virus, if confirmed to be present in these patients, derives from either wild strains or vaccine strains. In order to characterize the strains that may be present, we have carried out the detection of measles genomic RNA in peripheral mononuclear cells (PBMC) in eight patients with Crohn's disease, three patients with ulcerative colitis, and nine children with autistic enterocolitis. As controls, we examined healthy children and patients with SSPE, SLE, HIV-1 (a total of eight cases). RNA was purified from PBMC by Ficoll-paque, followed by reverse transcription using AMV; cDNAs were subjected to nested PCR for detection of specific regions of the hemagglutinin (H) and fusion (F) gene regions. Positive samples were sequenced directly, in nucleotides 8393-8676 (H region) or 5325-5465 (from noncoding F to coding F region). One of eight patients with Crohn disease, one of three patients with ulcerative colitis, and three of nine children with autism, were positive. Controls were all negative. The sequences obtained from the patients with Crohn's disease shared the characteristics with wild-strain virus. The sequences obtained from the patients with ulcerative colitis and children with autism were consistent with being vaccine strains. The results were concordant with the exposure history of the patients. Persistence of measles virus was confirmed in PBMC in some patients with chronic intestinal inflammation. [ABSTRACT FROM AUTHOR]

Rotavirus is the most common cause of severe gastroenteritis in young children; however, its pathogenesis and immunity are not completely understood. Even less well recognized is rotavirus-induced central nervous system (CNS) involvement, which has been associated with seizure, encephalopathy and death, among others. To elucidate the host response to rotavirus infection, we retrospectively examined neurotransmitter amino acids in the cerebrospinal fluid (CSF) of 19 children with CNS involvement associated with rotavirus infection. Subjects were classified into two groups: those with encephalopathy followed by prolonged seizure (encephalopathy group) and those who had experienced afebrile, brief cluster of seizures without encephalopathy (cluster group). The levels of glutamate, glycine, and taurine in the encephalopathy group were significantly higher than those in the cluster group. Increased levels of excitatory amino acids in the CSF may induce neurological disorders and be related to disorder severity. To the best of our knowledge, this is the first report regarding amino acids in the CSF obtained from patients with rotavirus-induced CNS involvement. Further study is necessary to elucidate the role of CSF amino acid levels in rotavirus-induced CNS involvement., (© 2014 Wiley Periodicals, Inc.)

Many reports in the field of childhood brain disorders have documented that brain-derived neurotrophic factor (BDNF) affects central nervous system (CNS) functions. In this clinical study, BDNF levels were evaluated in association with pediatric CNS infections. BDNF levels in the serum and cerebrospinal fluid (CSF) of 42 patients admitted during 5-year period, due to CNS infections, were measured by enzyme-linked immunosorbent assays (ELISAs). Control samples were collected from 108 patients with non-CNS infections (urinary tract infection, acute upper respiratory infection, acute gastroenteritis, etc.). Mean values of BDNF levels, at various ages, were determined and compared. BDNF levels were below the sensitivity of the ELISA in most CSF samples from the control group, but were significantly elevated in the patients with bacterial meningitis. The serum BDNF levels were elevated in all subgroups of patients with CNS infections, and the elevation was particularly notable in those with bacterial meningitis. BDNF expression in the CSF was correlated with CSF interleukin (IL)-6 levels as well as with blood platelet counts and neurological prognoses in those with bacterial meningitis. No correlation was found between BDNF levels and serum leukocyte numbers or C-reactive protein (CRP) levels. BDNF levels were found to be elevated in the serum and CSF of pediatric patients with CNS infections, particularly those with bacterial meningitis. Monitoring the changes in serum and CSF levels of BDNF may facilitate the diagnosis of acute meningitis and acute encephalopathy and allow the differential diagnosis of specific CNS infections.

Respiratory syncytial virus (RSV) infection in children can be associated with acute encephalopathy. However, the roles of cytokines in the cerebrospinal fluid (CSF) of such patients remain unevaluated. In this study, a profile of 17 cytokines was determined for eight RSV-infected children with neurological complications. In one patient with high levels of 13 cytokines, a cytokine storm was considered to have occurred. Interleukin (IL)-6, IL-8, monocyte chemoattractant protein (MCP)-1, and macrophage inflammatory protein (MIP)-1β levels were also high in other patients. These data suggest that chemokines in CSF play roles in neurological complications in RSV-infected children.

Background: Children infected with rotavirus often show increased levels of transaminase, and symptoms are characterized by white stool, similar to biliary atresia. Rotavirus infections are also sporadically accompanied with convulsions, encephalopathy and Reye syndrome. The aim of the present study was therefore to investigate transaminase and interleukin (IL)-6 levels in rotavirus infection, in order to better understand their clinical significance., Methods: Results of liver function tests, mainly the elevation of transaminase and IL-6 in rotavirus gastroenteritis with or without convulsions, were evaluated., Results: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were high in 23 of 26 samples (88.5%), and in three of 26 samples (11.5%), respectively. No significant differences in liver function tests could be found between the groups with or without convulsions. Three patients whose direct bilirubin levels were above the upper normal limit were all classified into the group without convulsions. Spearman's correlation coefficient was 0.89 between increasing AST levels and IL-6 levels., Conclusion: Rotavirus infection is occasionally accompanied with hepatitis, but only in a mild form, and does not correlate with neurological complications. High levels of transaminase might reflect high IL-6., (© 2011 The Authors. Pediatrics International © 2011 Japan Pediatric Society.)

We discovered a new cataract mutation, kfrs4, in the Kyoto Fancy Rat Stock (KFRS) background. Within 1 month of birth, all kfrs4/kfrs4 homozygotes developed cataracts, with severe opacity in the nuclei of the lens. In contrast, no opacity was observed in the kfrs4/+ heterozygotes. We continued to observe these rats until they reached 1 year of age and found that cataractogenesis did not occur in kfrs4/+ rats. To define the histological defects in the lenses of kfrs4 rats, sections of the eyes of these rats were prepared. Although the lenses of kfrs4/kfrs4 homozygotes showed severely disorganised fibres and vacuolation, the lenses of kfrs4/+ heterozygotes appeared normal and similar to those of wild-type rats. We used positional cloning to identify the kfrs4 mutation. The mutation was mapped to an approximately 9.7-Mb region on chromosome 7, which contains the Mip gene. This gene is responsible for a dominant form of cataract in humans and mice. Sequence analysis of the mutant-derived Mip gene identified a 5-bp insertion. This insertion is predicted to inactivate the MIP protein, as it produces a frameshift that results in the synthesis of 6 novel amino acid residues and a truncated protein that lacks 136 amino acids in the C-terminal region, and no MIP immunoreactivity was observed in the lens fibre cells of kfrs4/kfrs4 homozygous rats using an antibody that recognises the C- and N-terminus of MIP. In addition, the kfrs4/+ heterozygotes showed reduced expression of Mip mRNA and MIP protein and the kfrs4/kfrs4 homozygotes showed no expression in the lens. These results indicate that the kfrs4 mutation conveys a loss-of-function, which leads to functional inactivation though the degradation of Mip mRNA by an mRNA decay mechanism. Therefore, the kfrs4 rat represents the first characterised rat model with a recessive mutation in the Mip gene.

We report prolonged valganciclovir (VGCV) treatment of a symptomatic cytomegalovirus infection case. Automated auditory brainstem evoked response performed at 5 days of age revealed severe hearing impairment. Cranial magnetic resonance (MR) imaging at 11 days of age showed abnormal findings. At 5 weeks of age, VGCV was started. The viral load in blood cells, plasma, and urine decreased during the 6-week treatment. Because of improvement of hearing level and no adverse effects, VGCV was restarted for an additional 6 weeks. Neither the patient's hearing impairment nor results of cranial MR imaging have become worse in 6 months. It is crucial to gather information from as many cases as possible treated with VGCV to establish a standard protocol for VGCV treatment.

Background:   Neuromuscular disorders can be the cause of sudden death of infants because of their weakness and gastroesophageal reflux (GER)., Methods:   Muscle biopsy and genetic studies were performed by usual method., Results:   In this report four cases of infants with neuromuscular disorders (two cases of congenital myopathy and two cases of spinal muscular atrophy) who had unexpected cardiopulmonary arrest on arrival (CPAOA) are presented. Two of the cases did not show any symptoms, such as muscle weakness prior to CPAOA. The diagnosis was based on the results of the muscle biopsy and genetic examination., Conclusion:   These results suggest that sudden infant death caused by neuromuscular disorders should be considered., (© 2011 The Authors.Pediatrics International © 2011 Japan Pediatric Society.)

This study sought to determine diurnal variations in febrile convulsions, and to investigate whether such variations influenced the severity of febrile convulsions. The study involved 326 children, between ages 6 months and 6 years, with simple febrile convulsions. Data were collected systematically by interviewing witnesses within the week after febrile convulsions occurred. The frequency of febrile convulsions was approximately 5 times greater in the evening than in early morning. An adaptation curve revealed that the maximum occurrence of febrile convulsions was at 4:00 pm (4:00-4:59 pm), and the minimum, at 4:00 am (4:00-4:59 am), similar to the pattern of human body temperature. Temperature and seizure duration did not differ significantly between high-frequency and low-frequency zones (2:00-7:00 pm and 2:00-7:00 am, respectively) (high-frequency zone vs low-frequency zone, 39.20 degrees C (S.D., 0.68 degrees C) vs 39.22 degrees C (S.D., 0.64 degrees C) and 3.82 minutes (S.D., 5.27 minutes) vs 3.14 minutes (S.D., 3.19 minutes)). These results suggest that the circadian rhythm does not change seizure propensity, but its hourly occurrence is attributable to an elevation in the temperature set point in the 24-hour period. The prevention of recurrent febrile convulsions by rectal administration of anticonvulsants in high-frequency zones would be clinically helpful., (Copyright 2010 Elsevier Inc. All rights reserved.)

Background: In recent years an increase has been seen in the number of patients with severe atopic dermatitis (AD) accompanied with generalized typical eruptions. Some markers indicating the severity of the disease and symptom changes are very useful, and therefore the purpose of the present study was to investigate serum lactate dehydrogenase (LDH) as such a marker., Methods: A total of 58 children with AD were enrolled. The severity of the disease was graded on the basis of the extent of eruptions and the severity of atopic symptoms. The fraction of serum LDH, number of eosinocytes in the peripheral blood, and serum IgE levels were also determined., Results and Conclusion: There was a close correlation between the severity of cutaneous symptoms and serum LDH activity, and between severity and eosinocyte count, but no relationship was seen between serum IgE levels and severity of the disease. The aforementioned factors were determined in a time-related way. As the patients' condition improved, serum LDH activity tended to decline, but there were no consistent changes in eosinocyte count in the peripheral blood or serum IgE level. On LDH isozyme the levels of LDH4 and LDH5 were high. Tissue showed high LDH activity, especially in epidermides. These results suggest that serum LDH activity is a useful marker.

In order to better understand enteroviral encephalitis we investigated the clinical symptoms and several disease markers. Between 2000 and 2005 eight patients aged between 9 months and 5 years were admitted to our hospital with one case having sequela. Glutamic oxaloacetic transaminase (GOT), serum IL-6, and ferritin were elevated in most of the cases. Their IL-6 and diacron-reactive oxygen metabolites (d-ROM) in cerebral spinal fluid (CSF) were also high (86%). However, pleocytosis and high protein levels in CSF were rarely found. In viral loads of the first CSF, there were no differences between the patient with sequela and the ones without sequela. However, anti-glutamate receptor IgMdelta2 was only detected in the CSF of the patient with sequela. These findings suggest that the immunological phenomenon is more closely related to the development of sequela related to enteroviral encephalitis than other disease markers, such as inflammatory cytokine, free radicals, and viral loads. Therefore, a specific therapy against immunological status might decrease the sequela; however, further research is necessary to confirm this.

Objective: Kawasaki disease (KD) is a systemic vasculitis in childhood; its etiology is unknown. The possibility that KD is an infectious disease has been discussed and investigated for decades, in light of the implication that infections are involved in the pathogenesis of KD. Young children rely on their innate immune system for protection against virus and micro-organisms. Human mannose binding lectin (MBL) is a C-type serum lectin synthesized by the liver as an acute phase protein and it plays an important role in the innate immune system. Here, we investigate the relationship between the MBL gene polymorphisms and the occurrence of KD in the Japanese population., Method: The frequencies of the genotypes, defined as mutations in codons 52, 54 and 57, and the functional promoter variants of the MBL were determined in 45 patients with KD., Results: The MBL codon-54 polymorphism frequency of heterozygote (GGC/GAC) and promoter variants were significantly higher in the KD group than that in the control group (P < 0.05). Neither group showed codon 52 nor 57 polymorphisms., Conclusion: It is possible that mutations of the MBL gene might be related to the trigger of the pathogenesis of Kawasaki disease.

Severe combined immunodeficiency (SCID) is an inherited disease with profoundly defective T cells, B cells, and NK cells. X-linked severe combined immunodeficiency (X-SCID) is its most common form. In this report, we describe a 4-month old male with X-SCID who also showed opisthotonic posturing. Opisthotonus represents abnormal motor posturing and is defined as the posturing, in which the neck and back are arched posteriorly. The patient was referred to our hospital with liver dysfunction, respiratory distress, anal abscess, poor feeding and wasting; the patient appeared to suffer from severe and persistent infections. In fact, circulating T cells were not detectable, despite that the number of B cells was maintained in the normal ranges. Diagnosis of X-SCID was established by DNA analysis of the interleukin (IL)-2 receptor gamma chain gene; namely, we detected the novel mutation within exon 2 (221 C-->A), which leads to the substitution of tyrosine codon for stop codon (Y69stop). Computed tomography of the brain revealed mild atrophy, but no hemorrhage and no malformation. There were no pathological findings in the cerebrospinal fluid. Thus, the cause of opisthotonic posturing remains unknown. The patient died due to severe infection at the age of 7 months. It remains to be investigated to clarify the relationship between the mutation and clinical manifestations. In conclusion, we have identified the novel mutation in the IL-2 receptor gamma chain gene, which is associated with X-SCID. Furthermore, this is the first report that describes the patient with X-SCID accompanying opisthotonus.

Background: In the pathology of autoimmune hepatitis the immunity mechanism of T-helper 1 (Th1) and Th2 cells was recently evaluated. The purpose of the present study was to measure the mRNA levels in peripheral mononuclear cells and serum cytokines obtained from children with autoimmune hepatitis for a better understanding of the mechanism., Methods: Twenty-five patients with autoimmune hepatitis and seven controls were enrolled. mRNA levels in peripheral mononuclear cells and serum cytokines were measured using real-time polymerase chain reaction and immunoassay., Results: Serum interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) were rarely detected. In contrast the IFN-gamma/beta-actin mRNA levels were high., Conclusion: Autoimmune hepatitis is a Th1-predominant state, therefore immune modulation therapies that target the control of Th1 cytokines should be used.

The cause of influenza to the brain was investigated using the A/NWS/33 influenza virus infected BALB/c mouse model. NOS-2 mRNA levels in the infected mouse brain was greater than in control mice in all brain regions examined, particularly in the olfactory bulb and hippocampus by 1 day p.i. On the contrary, no differences in NOS-1 or NOS-3 mRNA levels were found between infected and control mice. There was also a marked increase in the levels of metabolites of nitric oxide in the olfactory bulb and hippocampus. Immunohistochemistry showed positive staining for anti-NOS-2 primarily in the hippocampus of infected mice. Further, anti-NOS-2 and GFAP staining was mostly found around capillary blood vessels of the hippocampus starting early in the course of the disease. These results indicate that the NWS enhances the activation of astrocytes and NOS-2 expression which in turn enhances NO production and the expansion of capillary blood vessels.

We describe a case of severe CINCA syndrome in a Japanese male infant. We recently managed with anti-interleukin 1 agent (anakinra). Anakinra immediately led to improvement of both the clinical symptoms and the laboratory findings.

Background: Epidemiologic studies of n-3 fatty acids (FAs) and risk of colorectal cancer have generated inconsistent results, and relations with precursor colorectal adenomas (CRA) have not been evaluated in detail. We here focused on possible associations of serum FAs with CRA in the Japanese population., Methods: We conducted a case-control study of 203 asymptomatic CRA cases (148 men, 55 women) and 179 healthy controls (67 men, 112 women) during 1997-2003 in Nagoya, Japan. Baseline information was obtained using a lifestyle questionnaire and serum FA levels were measured by gas chromatography., Results: A non-significant inverse association with CRA was observed for eicosapentaenoic acid (EPA) among women. Moreover, the concentrations of docosahexaenoeic acid (DHA), a major component of n-3 highly-unsaturated FAs (HUFAs), were significantly lower in cases in both sexes. In addition, serum concentrations of total FAs, saturated FAs (SFAs) and mono-unsaturated FAs (MUFAs) had strong positive links with CRA risk. In contrast, arachidonic acid (AA) and DHA were inversely related, with 66% and 59% risk reduction, respectively. Ratios of SFAs/n-3 PUFAs and SFAs/n-3 HUFAs exhibited significant positive relations with CRA risk but there was no clear link with n-6 PUFAs/n-3 PUFAs., Conclusions: Our findings suggest a promoting influence of SFAs and MUFAs along with a protective effect of DHA on CRA risk. However, further research is needed to investigate the observed discrepancy with the generally accepted roles of the AA cascade in carcinogenesis.

For a better understanding of the role of the viral load, free radicals, and cytokines in viral meningitis, we surveyed cerebrospinal fluid (CSF) obtained from patients below 1 year of age who showed positive for enterovirus. In their first examinations interleukin (IL)-6 and free radicals increased whereas pleocytosis was rarely observed. IL-6 decreased within the short period. Viral loads and free radicals increased simultaneously. IL-6 and free radicals of CSF are helpful for diagnosis and treatment of viral meningitis at an early stage., ((c) 2008 Wiley-Liss, Inc.)

Background: Chlamydia pneumoniae is a frequent causative agent of acute respiratory disease and has been recently reported as a possible cause of asthma. We investigated the prevalence of C. pneumoniae infections in childhood patients with acute exacerbations of asthma., Method: One hundred twenty-six childhood patients with acute exacerbations of asthma, 77 with acute bronchitis and 22 Respiratory syncytial virus infections were studied. Serum samples were obtained and tested for C. pneumoniae-specific IgM antibody by Enzyme-Linked ImmunoSorbent Assay (ELISA)., Results: C. pneumoniae IgM-positive results were observed in 48.4% (Index value>or=1.60) and 23% (Index value>or=1.10) of patients with acute exacerbations of asthma. The prevalence of C. pneumoniae-specific IgM was significantly higher in asthma cases than in other subjects (p<0.05)., Conclusion: Our data suggest that C. pneumoniae infection may trigger acute exacerbations of childhood asthma.

To better understand the role of nitric oxide (NO) in pediatric nephrotic syndrome, we measured nitrite/nitrate (NOx) [NO2- and NO3-] in serum obtained from patients with several pediatric kidney diseases and investigated the locations of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS). NOx in serum showed significantly higher levels than those in healthy controls (mean +/- SE: 297 +/- 55.7 vs. 158 +/- 13.1 pmol/10 microl). There was no significant difference between six patients with frequent relapse and five patients with nonfrequent relapse. The studies with immunostaining of iNOS and nitrotyrosine were negative for glomerulus in patients with nephrotic syndrome. Those findings suggest that NOx might indirectly influence disease progression in nephrotic syndrome.

Neonatal onset multisystem inflammatory disease (NOMID), which is also known as chronic infantile neurological cutaneous and articular syndrome, is a rare disease that is characterized by the triad of cutaneous rash, chronic meningitis and arthropathy. The long-term prognosis is poor, with progressive deafness and visual impairment, and worsening of the central nervous system manifestations. Some fatal cases have been reported secondary to infection, vasculitis and amyloidosis. We recently managed a typical case of NOMID where the combined treatment of continuous hemodiafiltration and steroid pulse therapy was effective. The patient showed repeated flare ups of fever, arthralgia and meningitis accompanied with high levels of cytokines. The effect was temporary, but useful in recovery from such a serious condition.