MEF2C transcription factor is associated with the genetic and epigenetic risk architecture of schizophrenia and improves cognition in mice.

Large-scale consortia mapping the genomic risk architectures of schizophrenia provide vast amounts of molecular information, with largely unexplored therapeutic potential. We harnessed publically available information from the Psychiatric Genomics Consortium, and report myocyte enhancer factor 2C (MEF2C) motif enrichment in sequences surrounding the top scoring single-nucleotide polymorphisms within risk loci contributing by individual small effect to disease heritability. Chromatin profiling at base-pair resolution in neuronal nucleosomes extracted from prefrontal cortex of 34 subjects, including 17 cases diagnosed with schizophrenia, revealed MEF2C motif enrichment within cis-regulatory sequences, including neuron-specific promoters and superenhancers, affected by histone H3K4 hypermethylation in disease cases. Vector-induced short- and long-term Mef2c upregulation in mouse prefrontal projection neurons consistently resulted in enhanced cognitive performance in working memory and object recognition paradigms at baseline and after psychotogenic drug challenge, in conjunction with remodeling of local connectivity. Neuronal genome tagging in vivo by Mef2c-Dam adenine methyltransferase fusion protein confirmed the link between cognitive enhancement and MEF2C occupancy at promoters harboring canonical and variant MEF2C motifs. The multilayered integrative approaches presented here provide a roadmap to uncover the therapeutic potential of transcriptional regulators for schizophrenia and related disorders.

Microspectrophotometric analysis of nuclear DNA in Chara zeylanica.

Microspectrophotometric analysis of the DNA content of nuclei in various parts of Chara zeylanica Willd. revealed that the amount of DNA in the nucleus of an internodal cell equals twice the amount of DNA in the nucleus of a sperm, while the half-anaphase stage of the same nodal cells contains the same amount of DNA as the nuclei of the male gametes. The DNA content of the nuclei of internodal cells may rise as much as 50 times higher than that of the gametes. However, in the oldest (most basal) internodal cells, the DNA content of the minute nuclei falls again to the basic (1 C) amount. Measurements of sister nuclei derived by amitosis indicated that both nuclei have equal amounts of DNA; this was interpreted as further evidence that amitosis is not a disorganized process or manifestation of degeneration. The bearing of these analyses on the question of the site of meiosis in these plants is discussed.

Comparative usefulness of C-reactive protein and erythrocyte sedimentation rate in juvenile rheumatoid arthritis.

OBJECTIVE: To compare serial C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels in juvenile rheumatoid arthritis (JRA) patients and investigate their application as diagnostic parameters and prognostic predictive factors. METHODS: We carried out retrospective chart review among JRA patients who were followed-up at the National Taiwan University Hospital (NTUH) between 1994 and 2005. RESULTS: Thirty-nine girls and 68 boys were included in this study. At the time of diagnosis, the prevalence of ESR was significantly greater than that of CRP (86.8% vs. 47.2%, p < 0.05). ESR revealed more responsiveness to treatment compared to CRP (SRMs were -0.69 and -0.31, respectively). At the time of diagnosis, high CRP levels (>or= 5mg/dL) correlated with poor therapeutic response, as do positive CRP (> 0.8 mg/dL) and high ESR levels (> 40 mm/h) after treatment for six months. Overall, initial high CRP levels (>or= 5mg/dL) demonstrated the strongest predictive role of failure of the first remission. CONCLUSION: For disease diagnosis, ESR can be a better parameter than CRP but a high initial CRP level can strongly predict treatment failure of the first remission.

Effects of ascorbate in microdialysis perfusion medium on the extracellular basal concentration of glutamate in rat's striatum.

There are many evidences suggest that ascorbate in the extracellular space can affect glutamate concentration in the rat's brain. In this report, we studied how ascorbate in microdialysis perfusion medium affected glutamate level at the striatum in freely-moving rats. Three perfusion mediums were used: 0, 250, and 400 microM of ascorbate in perfusion medium. The extracellular basal concentrations of glutamate were determined to be 1.29+/-0.52 microM for the no ascorbate group, 0.86+/-0.35 microM for the low ascorbate group and 4.76+/-1.48 microM for the high ascorbate group. By using 400 microM of ascorbate in a perfusion medium, we found that the extracellular basal concentration of glutamate significantly increased and its in vivo recovery significantly decreased. This indicated that ascorbate concentration in a perfusion medium was important and must be carefully considered while using microdialysis technique to monitor glutamate concentration in vivo.

Ataxia telangiectasia: report of two cases.

Ataxia telangiectasia (A-T) is a rare autosomal recessive multisystem disease. The diagnosis of A-T is based on the typical clinical picture: ataxia and telangiectasia. However, an increase in (alpha-fetoprotein (AFP) level and the identification of the A-T mutated gene (ATM) assist in an early diagnosis. Here we report two cases of A-T diagnosed in our hospital (case 1: a 7-year-old boy; case 2: an 8-year-old girl). Both of these patients had typical clinical pictures of ataxia and telangiectasia, AFP was also increased (case 1:471.2 ng/dL; case 2: 196 ng/dL). T-cell dysfunction was noted in both patients. Case 1 had IgG2 deficiency and case 2 had IgA, IgG2 and IgG3 deficiency. Case 2 developed malignant lymphoma at 9 years of age and died of pneumonia with respiratory failure at 10 years of age. Because of rhe rarity of A-T in Taiwan, we report two cases to help pediatricians make an early diagnosis of A-T if they have a patient with progressive ataxia and oculocutaneous telangiectasia.

Guillain-Barré syndrome in children: a cooperative study in Taiwan.

Seventy-two children with Guillain-Barré syndrome (GBS), diagnosed at 11 major teaching hospitals in Taiwan during the period 1986-1990, were studied retrospectively. There were 44 males and 28 females ranging in age from 7 months to 15 years. Preceding events could be traced in 61 patients (85%), including antecedent infection in 59 patients and previous vaccination in 2. As well as the consistent pictures of progressive weakness and generalized hyporeflexia, there were sensory complaints (26%), cranial nerve lesions (46%), respiratory failure (14%) and autonomic dysfunction (25%). Motor symptoms reached a maximum within 20 days in 88% of the patients, with the plateau lasting less than 2 weeks in 75%, and became stable within 3 months in 76%. Overall outcome showed complete recovery in 73% of the patients within 6 months after onset. Four (5.6%) had recurrence, and there was no mortality. The present study revealed that the annual incidence of GBS in Taiwan can be estimated roughly as 0.66 per 100,000 and that the course of childhood GBS is relatively benign.

Alice in Wonderland syndrome as a presenting symptom of EBV infection.

Four Chinese patients (2 boys, 2 girls), ages 4-9 years, who had episodes of perception error of body schema and objects are reported. The metamorphopsia, which had been named Alice in Wonderland syndrome, is the major presentation. All of them were proved to have acute Epstein-Barr virus infection, as documented by positive heterophil antibody test and/or positive IgM antibody to Epstein-Barr virus capsid antigen. The duration of the perception disorder ranged from 1 week to 3 months. We believe that any young child presenting with Alice in Wonderland syndrome should undergo examination for Epstein-Barr virus infection; complete recovery from the disorder can be expected.

Tentorial subdural hemorrhage in term newborns: ultrasonographic diagnosis and clinical correlates.

Tentorial subdural hemorrhage with its supratentorial and infratentorial extensions were diagnosed by cranial ultrasonography and computed tomography in 9 term newborns. Vacuum extraction or forceps delivery was used in 6 patients. Abnormal neurologic manifestations developed after a period of normality in 8 patients. Increased intracranial pressure was the most common presentation. All patients had hemorrhage at the falcotentorial junction near the incisura; 5 also had hemorrhage around the tentorial leaflet. Posterior fossa retrocerebellar subdural hemorrhage developed in 5 patients and posterior interhemispheric subdural hemorrhage developed in 4. All 6 patients who received conservative treatment had normal neurodevelopmental outcomes. Of the other 3 patients upon whom suboccipital craniotomies were performed, only 1 had a normal outcome. Although it localized the tentorial subdural hemorrhage either at the incisura area or at the tentorial leaflet, ultrasonography failed to identify all patients with retrocerebellar or posterior interhemispheric subdural hemorrhage. Parturitional tentorial subdural hemorrhage may not be uncommon. Ultrasonography and computed tomography are complementary in the diagnosis. Surgical decompression of the posterior fossa subdural hematoma is necessary only in the presence of acute hydrocephalus or signs of brainstem compression.

Reversal of diastolic cerebral blood flow in infants without brain death.

The reversal of diastolic cerebral blood flow has been regarded as a characteristic waveform of brain death and a useful confirming sign. We report 2 patients who had diastolic flow reversal but survived. One, a 1-month-old boy with status epilepticus, had reversal of diastolic cerebral blood flow detected by Doppler ultrasound soon after admission. Reversal disappeared after medical management for increased intracranial pressure and seizure control. He recovered without sequelae. The other, a 6-month-old girl with choroid plexus papilloma, had reversal of diastolic flow during abrupt clinical deterioration. Emergent surgical removal of the tumor was performed and she survived with hemiparesis and psychomotor retardation. Our patients demonstrated that even in the presence of diastolic reversal of cerebral blood flow, prompt and effective treatment can avoid a fatal outcome.

Cerebral perfusion in children with Alice in Wonderland syndrome.

Alice in Wonderland syndrome (AIWS) is characterized by visual hallucinations and bizarre perceptual distortions. Technetium-99m hexamethylpropyleneamine tomography (SPECT) brain scans were performed in four patients during the acute stage of AIWS. Two patients were demonstrated to have Epstein-Barr virus infections. One had abnormal (EEG) findings. The visual-evoked potential, cranial CT, and MRI findings were negative. The decreased cerebral perfusion areas in all patients were near the visual tract and visual cortex. All involved some regions of the temporal lobe. In most patients with AIWS, the EEG, CT, and MRI are unable to determine the precise pathologic areas. However, a SPECT brain scan may demonstrate abnormal perfusion areas and explain the clinical presentations.

Continuous infusion of vasopressin in comatose children with neurogenic diabetes insipidus.

Three comatose children with neurogenic diabetes insipidus were treated with intravenous infusion of vasopressin. The infusion of vasopressin was started at a dose of 1.3 to 2.7 mU/kg/h as soon as diabetes insipidus was diagnosed. The effect (urine flow < 2 ml/kg/h with increased specific gravity) was noted in 1 to 6 hours. The infusion rate of vasopressin was adjusted according to urine flow rate which was usually kept around 65 ml/100 kcal metabolized/day. Hypernatremia was corrected 17 to 53 hours after the initiation of infusion of vasopressin. The levels of sodium stayed between 127 and 151 mmol/l during a period of 2.5 to 22 days until the patients' death due to the termination of respiratory support or cardiac decompensation. A continuous infusion of vasopressin offered the advantage of rapid onset and termination of effect and therefore could be easily titrated. It seems a rational therapy for comatose children with neurogenic diabetes insipidus.

Aicardi's syndrome in a female infant with a family history of miscarried male siblings.

Aicardi's syndrome is thought to be an X-linked genetic disease, although the mechanism for transmission remains uncertain. We report on a four-month-old female patient with Aicardi's syndrome. She was born prematurely at 28 weeks' gestation, weighing 1,500 g. Asymmetric myoclonic jerks developed at one month of age. Her left eye showed chorioretinal lacunae and a coloboma on the optic disc, while the right eye was microphthalmic with total retinal detachment. A CT scan disclosed heterotopia and dysgenesis of the corpus callosum. Abnormal development of the thoracic vertebrae was also evident. The most remarkable aspect of this case was that the patient's mother had suffered three miscarriages. Two are known to have been male, but the other gender is unknown. This family history may support the theory that there is a factor, lethal for males, involved in the genetic transmission of Aicardi's syndrome.

Enamel pitting in childhood tuberous sclerosis.

Dental enamel pitting was studied as a diagnostic sign of pediatric tuberous sclerosis (TSC). Thirteen patients aged 2.5 to 18 years with varying degrees of TSC were evaluated. They were checked for the presence of enamel pitting by the use of two to three drops of dental plaque disclosing stain which was applied to the labial surfaces of dry teeth. This technique provides a remarkable color contrast allowing for the detection of many small and subtle enamel pits. A control group of 39 unrelated patients without TSC were also examined. A total of 77% of TSC patients (10/13) revealed enamel pitting, compared with 13% of controls. The distribution of enamel pitting among TSC patients and normal controls of each sex was statistically significant. The total number of enamel pits in each patient varied from 1 to 26 and increased with age; 90% of the teeth with enamel pitting displayed one to two pits per tooth. The youngest patient with enamel pitting was 5 years old. The simplicity of this test and the high probability of pitting in TSC make the examination useful in the assessment of patients in whom the diagnosis of this serious genetic disease is being considered.

Association of allergy with Tourette's syndrome.

In our clinical practice, we often encounter signs and symptoms of allergy, such as rhinitis and asthma, in patients with Tourette's syndrome (TS). Some of the allergic manifestations are similar to the oral tics or motor tics found in TS patients. To clarify the association between TS and allergy, we evaluated 72 consecutive patients with TS from 1 September 1996 through 31 August 1997. The diagnosis of TS was based on the Diagnostic and Statistical Manual of Mental Disorders diagnostic criteria. Sixty-five boys and 7 girls, 4 to 17 years old (9.4 +/- 3.1 yr) were evaluated using the Multiple Allergens Simultaneous Tests (MAST) for the detection of total and specific immunoglobulin. Forty-five patients had positive results, of whom 41 (56.9%) had clinical evidence of allergy. The prevalence of allergy in the local population as reported by The International Study of Asthma and Allergy in Childhood Taiwan Group (1994) was 44.3% (33.5% with allergic rhinitis and 10.8% with asthma). These subjects served as controls. Comparing the number of patients with clinical evidence of allergy in the MAST positive group (56.9%) of TS patients with the control group (44.3%), the difference was significant++ (p < 0.05). The prevalence of allergy in TS patients in our study was significantly higher than in the general population. TS had an association with allergy.

Maple syrup urine disease: report of two cases.

Two cases of maple syrup urine disease (MSUD) are reported. Case 1 was a 10-day-old male infant who had cyanotic episodes and recurrent generalized convulsions; the odor of burned sugar from the body and urine was also noted. Plasma and urine amino acid analysis disclosed a marked increase in the concentration of branched chain amino acids (BCAA). As a result of a BCAA-free diet and mega-doses of thiamine, the condition stabilized. However, the patient was lost to follow-up and expired at two months of age due to inadequate management. Case 2 was a 20-day-old female infant with poor feeding, vomiting for one week, generalized convulsions and a peculiar burned sugar smell from the body and urine. Based on our experience with the first case, MSUD was suspected, and the infant was treated accordingly. However, subsequent follow-up revealed delayed developmental milestones. We present the first two reported cases of MSUD in Taiwan and review the relevant literature.

Early diagnosis of a vein of Galen aneurysm: report of a case.

Congenital vascular malformation with an aneurysm of the vein of Galen is rarely seen, particularly in the prenatal period. With the advancement of diagnostic techniques such as ultrasonography, we were able to detect a case prenatally and to diagnose it postnatally.

Excitatory and inhibitory amino acid levels in the cerebrospinal fluids of children with neurological disorders.

Measurement of amino acid levels in the cerebrospinal fluid (CSF) of children with various neurological disorders was performed with high performance liquid chromatography (HPLC). Glutamate increased in patients with bacterial meningitis, aseptic meningitis and encephalitis. Aspartate increased in bacterial meningitis and seizure disorders. Glycine increased in both bacterial and aseptic meningitis. Taurine increased in bacterial meningitis and encephalitis. GABA, the main inhibitory amino acid, increased in encephalitis. Excitatory and inhibitory amino acids are richly distributed in brain tissue and are related to neuron activity. Changes in amino acid levels in the CSF may reflect the pathologic state and severity of brain insults, and may be useful in monitoring disease processes. Further study is necessary to determine whether CSF aminos acid levels have a role in practical clinical application.

Tuberous sclerosis with visceral organ involvement.

This study is to determine the incidence of visceral organ involvement in tuberous sclerosis (TS). We reviewed 30 cases of TS diagnosed between 1987 to 1997. There were 17 males and 13 females, ages ranged from one day old to 17 years old. Among the 30 cases, 25 patients had seizures and skin manifestations; 24 had cerebral tubercles; 10 had heart involvement (9 rhabdomyoma, 1 dilated cardiomyopathy); 4 had kidney involvement (3 polycystic kidney disease, 1 renal hamartoma); and 3 had retinal astrocytic hamartoma. Based on our study, the most common visceral organs involved were the heart and kidney. Among the ten patients with cardiac rhabdomyoma, six were less than 1 year old (mean age 1.6 +/- 2.2 years old). One newborn presented with a cardiac mass diagnosed by prenatal sonography and another newborn, noted to have tachycardia after birth, underwent surgical intervention due to impending heart failure. Four patients had kidney abnormalities; three were less than 5 years old (mean age 5.2 +/- 5.2 years). During this 10 year period, there was no mortality seen among patients with visceral organ involvement. We suggest that clinicians treating patients with TS should not overlook the visceral organs, especially heart and kidney, which, if involved can have significant morbidity.