Transaminase in rotavirus gastroenteritis.

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.

Myopathy and neurogenic muscular atrophy in unexpected cardiopulmonary arrest.

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.

Anti-glutamate receptor antibodies in pediatric enteroviral encephalitis.

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.

Viral loads of cerebrospinal fluid in infants with enterovirus meningitis.

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.

A case report of neonatal onset multisystemic inflammatory disease in Japan treated with continuous hemodiafiltration and steroid pulse therapy.

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.

Virological and immunological characteristics of fatal virus-associated haemophagocytic syndrome (VAHS).

We report three infants and one teenager with fatal virus-associated haemophagocytic syndrome (VAHS). Two infants were admitted to our hospital because of cardio-pulmonary arrest (CPA). The third infant was admitted to our department because of fever and liver dysfunction, and he was diagnosed as combined immunodeficiency with predominant T cell defect. The teenager was diagnosed as systemic lupus erythema (SLE) when she was 10 years old and admitted to our department because of fever and thrombocytopenia . The histological findings for the four patients' organs revealed many haemophagocytic cells . The patients were infected by Parainfluenza virus type 2 (PIV2), Enterovirus (EV), Cytomegalovirus (CMV), and Epstein-Barr virus (EBV), respectively. Their laboratory data revealed elevated levels of ferritin and IL-6, which also suggested virus-associated haemophagocytic syndrome (VAHS). Although aggressive therapies were performed in all cases, the outcome was fatal. Further investigation would be needed to clarify the mechanism of VAHS and an effective therapeutic regimen is needed.

Combined treatment of steroids and cyclosporine in Kimura disease.

Kimura disease is a rare but distinctive chronic eosinophilic inflammatory disorder that is characterized by tumor-like lesions in the soft tissue and lymph nodes of the head and neck or parotid gland. Recently, many immunopathogenetic features of underlying T lymphocytes and related cytokines have been noted in Kimura disease. However, few previous studies have investigated the serial levels of cytokines in children. In this report we describe an 11-year-old Japanese boy with relapsing Kimura disease. Before the diagnosis of Kimura disease, the patient had a swelling on his left neck. Steroids were effective, but the tumor relapsed within a few months as the steroids were tapered. He was treated with steroids and cyclosporine. This treatment was done by measuring serial levels of serum soluble interleukin-2 receptor, interleukin-4, interleukin-5, and eosinophil cationic protein. These results suggest the activation of T-helper cells and T-helper 2 cytokines, that after activated B cells and eosinophilic infiltration play an important role in Kimura disease, and that cyclosporine suppresses the activity of this disease.

Diagnostic and predictive value of CSF d-ROM level in influenza virus-associated encephalopathy.

The aim of this study was to assess the validity of serum and CSF oxidative status of patients with IE in their initial stage through the d-ROM (Diacron-Reactive Oxygen Metabolites, Italy) test, compared to those with other neurological diseases. The study was conducted on the following four groups: (1) influenza virus-associated encephalopathy (IE, n = 8), including four patients showing neurological sequelae or mortal; (2) influenza virus-associated febrile seizures (IFS, n = 11); (3) febrile convulsion (FC, n = 10): (4) enterovirus-associated encephalopathy (EE, n = 4), including one patient with neurological sequelae. The CSF d-ROM levels in the IE group were significantly higher than those in the IFS and the FC groups but not in the EE group. In addition, general laboratory findings such as leukocytes, platelets, C-reactive protein, aspartate aminotransferase, creatinine, creatinine kinase and LDH, including interleukin-6 (IL-6), were analyzed in each group. The CSF d-ROM levels in the IE group were significantly higher than those in the IFS and FC groups but not in the EE group. As for the serum d-ROM levels and general laboratory findings, with the exception of CSF IL-6 levels in IE, no significant differences were detected compared with the other groups. In patients with IE, the CSF d-ROM levels could be a valid predictive biomarker of the severity, and oxidative stress may be related to the pathogenesis of IE.

A case of Reye syndrome with rotavirus infection accompanied with high cytokines.

We report on a 23-month-old boy with a rare complication of rotavirus gastroenteritis. He was diagnosed as acute encephalopathy with DIC accompanied with high levels of cytokines. The liver pathology also revealed mild infiltration and fatty changes. He was suspected to be suffering from a cytokine storm followed by Reye syndrome.

Beta-catenin interacts with the FUS proto-oncogene product and regulates pre-mRNA splicing.

BACKGROUND & AIMS: beta-Catenin is a downstream effector of the Wnt signaling pathway and is believed to exert its oncogenic function by activating T-cell factor (TCF)/lymphoid enhancer factor (LEF) family transcriptional factors. However, it is still uncertain whether the diverse effects of beta-catenin are caused solely by aberrant gene transactivation. In this study, we used a proteomics approach to obtain further insight into the functional properties of nuclear beta-catenin. METHODS: The protein assembly of a native beta-catenin-containing complex in nuclear extracts from a colorectal cancer cell line, DLD-1, was identified using immunoprecipitation and mass spectrometry. RESULTS: beta-Catenin physically interacted with fusion (FUS)/translocated in liposarcoma (TLS) and various RNA-binding proteins. The expression of FUS/TLS was closely associated with the accumulation of beta-catenin and with the undifferentiated status of intestinal epithelial cells. The transient transfection of FUS suppressed beta-catenin-evoked gene transactivation of TCF/LEF, and beta-catenin transfection affected the splicing pattern of the E1A minigene and induced a novel splicing variant of estrogen receptor (ER)-beta exerting a dominant-negative activity. CONCLUSIONS: Human cancer expresses a large variety of alternatively spliced messenger RNA (mRNA), but the precise molecular mechanisms responsible for cancer-related alternative splicing are largely unknown. In this study, we demonstrated the interaction of beta-catenin with FUS/TLS and other RNA-binding proteins involved in the regulation of pre-mRNA splicing. Certain mRNA splicing abbreviations seen in human cancers may be induced by the activation of the Wnt signaling pathway.

Efficacy of plasma exchange and methylprednisolone pulse therapy on influenza-associated encephalopathy.

Patients with a new type of influenza-associated encephalopathy with high mortality are increasing in Japan and the United States. We present three patients treated with methyprednisolone pulse treatment and plasma exchange to remove cytokines, and all three patients recovered without severe sequela. IL-6 decreased dramatically after the start of the plasma exchange and methyprednisolone. Therefore when influenza-associated encephalopathy is actually diagnosed, steroid pulse therapy should be started at an early stage, and when signs of DIC and/or MOF appear, plasma exchange is recommended to remove the cytokines and NOx.

Clinical application of rapid assay of interleukin-6 in influenza-associated encephalopathy.

The characteristics of influenza-associated encephalopathy is the high mortality and nimble progress with coma which appears in general cases within 48 hours. Most of patients show no abnormalities in the standard blood checks on admission or in early stage. In this study we investigated if a rapid assay of interleukin (IL)-6 is useful in influenza-associated encephalopathy in early stages. The levels of IL-6 in patients with influenza-associated encephalopathy did not show any significant difference compared with those in patients with febrile convulsion and rotavirus-associated convulsion. However the levels of IL-6 in severe cases were significantly higher than those of mild cases with influenza-associated encephalopathy. Consequently the rapid assay of serum IL-6 is useful to evaluate and decide the therapies.

Sudden infant death syndrome due to parainfluenza virus 2 associated with hemophagocytic syndrome.

We report a child with Sudden Infant Death Syndrome (SIDS), aged 16 months. The histological findings of tonsils, spleen, and bone marrow revealed many hemophagocytic cells. Parainfluenza virus type 2 (PIV2) was cultured in the nasopharynx and detected by reverse-transcription (RT)-PCR in liver tissue and bone marrow. His laboratory data of elevated level of ferritin and IL-6 suggested hemophagocytic syndrome (HPS). It is suspected that PIV2 infection in infants is a risk factor for SIDS.

Serum and cerebrospinal fluid nitrite/nitrate levels in patients with rotavirus gastroenteritis induced convulsion.

Nitric oxide (NO) is a highly reactive free radical that is involved in a variety of different biological process. In recent reports, the putative role of NO in the neuropathogenesis of brain inflammation has been demonstrated. And then the relation between neuronal NO and convulsive seizures induced by virus has been suggested. However, there are few reports about NO in vivo under viral neurological infections. In order to evaluate the relation between NO production and neurological disorders induced by viral infection, sixty-six cases including 11 patients with rotavirus gastroenteritis admitted for convulsions were examined in this study. NO metabolites (NOx) levels in both serum and cerebrospinal fluid obtained from rotavirus gastroenteritis patients with convulsion were much higher than in those of patients with purulent meningitis, encephalitis, febrile convulsion or in the control group. There was a relative correlation between IL-6 and NOx in some cases. These results indicated that NO may have a pathophysiological role in convulsions associated by rotavirus infection either through indirect or direct effects of NO. Consequently, NOx inhibitors might be helpful for the treatment of rotavirus encephalopathy.

Clinical characteristics and gB genotype of cytomegalovirus infection in Japan.

To investigate the role of cytomegalovirus (CMV) gB genotypes, we examined the relationship between gB genotypes and clinical features in 19 patients with CMV infection. We analyzed 9 immunocompetent patients (1A) and 5 patients (1B) with various basic disorders in the symptomatic group. Five patients were enrolled in the asymptomatic group (2). To investigate gB genotypes, PCR was performed with oligonucleotide primers using clinical specimens and PCR products were digested with HinfI and RsaI We determined the PCR genotype by using restriction fragment length polymorphism (RFLP) analysis patterns. In the symptomatic group (1A and 1B), all clinical specimens were identified as gB genotype 1. In the asymptomatic group (2), only 2 specimens were identified as gB genotype 3. The distribution of CMV gB genotypes in clinical specimens was as follows: gB 1-17 out of 19 (89.5%) and gB 3-2 out of 19 (10.5%). Our data revealed that gB genotype 3 CMV did not show symptomatic infection.