[Analysis of the clinical features and the risk factors of severe human metapneu movirus-associated community acquired pneumonia in children].

Objective: To investigate the clinical characteristics and the risk factors of severe human metapneumovirus (hMPV)-associated community acquired pneumonia (CAP) in children. Methods: A retrospective case summary was conducted. From December 2020 to March 2022, 721 children who were diagnosed with CAP and tested positive for hMPV nucleic acid by PCR-capillary electrophoresis fragment analysis of nasopharyngeal secretions at the Yuying Children's Hospital, the Second Affiliated Hospital of Wenzhou Medical University were selected as the research objects. The clinical characteristics, epidemiological characteristics and mixed pathogens of the two groups were analyzed. According to CAP diagnostic criteria, the children were divided into the severe group and the mild group. Chi-square test or Mann-Whitney rank and contrast analysis was used for comparison between groups, while multivariate Logistic regression was applied to analyze the risk factors of the severe hMPV-associated CAP. Results: A total of 721 children who were diagnosed with hMPV-associated CAP were included in this study, with 397 males and 324 females. There were 154 cases in the severe group. The age of onset was 1.0 (0.9, 3.0) years, <3 years old 104 cases (67.5%), and the length of hospital stay was 7 (6, 9) days. In the severe group, 67 children (43.5%) were complicated with underlying diseases. In the severe group, 154 cases (100.0%) had cough, 148 cases (96.1%) had shortness of breath and pulmonary moist rales, and 132 cases (85.7%) had fever, 23 cases (14.9%) were complicated with respiratory failure. C-reactive protein (CRP) was elevated in 86 children (55.8%), including CRP≥50 mg/L in 33 children (21.4%). Co-infection was detected in 77 cases (50.0%) and 102 strains of pathogen were detected, 25 strains of rhinovirus, 17 strains of Mycoplasma pneumoniae, 15 strains of Streptococcus pneumoniae, 12 strains of Haemophilus influenzae and 10 strains of respiratory syncytial virus were detected. Six cases (3.9%) received heated and humidified high flow nasal cannula oxygen therapy, 15 cases (9.7%) were admitted to intensive care unit, and 2 cases (1.3%) received mechanical ventilation. In the severe group, 108 children were cured, 42 children were improved, 4 chlidren were discharged automatically without recovery and no death occurred. There were 567 cases in the mild group. The age of onset was 2.7 (1.0, 4.0) years, and the length of hospital stay was 4 (4, 6) days.Compared with the mild group, the proportion of children who age of disease onset <6 months, CRP≥50 mg/L, the proportions of preterm birth, congenital heart disease, malnutrition, congenital airway malformation, neuromuscular disease, mixed respiratory syncytial viruses infection were higher (20 cases (13.0%) vs. 31 cases (5.5%), 32 cases (20.8%) vs. 64 cases (11.3%), 23 cases (14.9%) vs. 44 cases (7.8%), 11 cases (7.1%) vs. 18 cases (3.2%), 9 cases (5.8%) vs. 6 cases (1.1%), 11 cases (7.1%) vs. 12 cases (2.1%), 8 cases (5.2%) vs. 4 cases (0.7%), 10 cases (6.5%) vs. 13 cases (2.3%), χ2=0.42, 9.45, 7.40, 4.94, 11.40, 8.35, 3.52, 6.92, all P<0.05). Multivariate Logistic regression analysis showed that age<6 months (OR=2.51, 95%CI 1.29-4.89), CRP≥50 mg/L (OR=2.20, 95%CI 1.36-3.57), prematurity (OR=2.19, 95%CI 1.26-3.81), malnutrition (OR=6.05, 95%CI 1.89-19.39) were the independent risk factors for severe hMPV-associated CAP. Conclusions: Severe hMPV-associated CAP is most likely to occur in infants under 3 years old and has a higher proportion of underlying diseases and co-infection. The main clinical manifestations are cough, shortness of breath and pulmonary moist rales, fever. The overall prognosis is good. Age<6 months, CRP≥50 mg/L, preterm birth, malnutrition are the independent risk factors for severe hMPV-associated CAP.

Absence of the adenosine A2A receptor confers pulmonary arterial hypertension and increased pulmonary vascular remodeling in mice.

BACKGROUND: Pulmonary arterial hypertension (PAH) is characterized by sustained elevation of pulmonary vascular resistance resulting from endothelial and smooth muscle cell dysfunction and collagen deposition in pulmonary vascular walls. In this study, we investigated the role of the adenosine A(2A) receptor (A(2A)R) in the development of PAH by determining the effect of genetic inactivation of A(2A)Rs on pulmonary vascular remodeling in mice. METHODS AND RESULTS: We characterized hemodynamic, histological and ultrastructural changes in pulmonary vascular remodeling in A(2A)R knockout (KO) mice compared with their wild-type (WT) littermates after exposure to normoxia and hypoxic conditions. After exposure to normoxia, compared to WT mice, A(2A)R KO mice displayed: (1) increased right ventricular systolic pressures and an elevated ratio of the right ventricle over left ventricle plus septum (Fulton index), (2) increased wall area and thickness as well as enhanced smooth muscle actin immunoreactivity in pulmonary resistance vessels, (3) increased proliferating cell nuclear antigen-positive cells in pulmonary resistance vessels and (4) increased smooth muscle cells hypertrophy and collagen deposition in the adventitia of pulmonary arteriole walls as revealed by electron microscope. By contrast, histological analysis revealed no features of hypertensive nephropathy in A(2A)R KO mice and there was no significant difference in systemic blood pressure, and left ventricular masses among the 3 genotypes. Furthermore, following chronic exposure to hypoxia, A(2A)R KO mice exhibited exacerbated elevation in right ventricular systolic pressure, hypertrophy of pulmonary resistance vessels and increased cell proliferation in pulmonary resistance vessels, compared to WT littermates. Thus, genetic inactivation of A(2A)Rs selectively produced PAH and associated increased smooth muscle proliferation and collagen deposition. CONCLUSIONS: Extracellular adenosine acting at A(2A)Rs represents an important regulatory mechanism to control the development of PAH and pulmonary vascular remodeling.

Establishment, characterization, virus susceptibility and transfection of cell lines from cobia, Rachycentron canadum (L.), brain and fin.

Establishment and characterization of two cobia, Rachycentron canadum, cell lines derived from cobia brain (CB) and cobia fin (CF) are described. Caudal fin and brain from juvenile cobia were dissociated for 30 and 10 min, respectively, in phosphate-buffered saline containing 0.25% trypsin at 25 degrees C. The optimal culture condition for both dissociated cells (primary cell culture) was at 28 degrees C in Leibovitz-15 medium containing 10% foetal bovine serum. The cells have been sub-cultured at a ratio of 1:2 for more than 160 passages over a period of 3 years. Origin of the cultured cells was verified by comparison of their sequences of mitochondrial cytochrome oxidase subunit I genes (cox I) with the cox 1 sequence from cobia muscle tissue. The cell lines showed polyploidy. No mycoplasma contamination was detected. Susceptibility to grouper iridovirus was observed for the CB cell line but not the CF cell line. Both cell lines expressed green fluorescent protein after being transfected with green fluorescent reporter gene driven by the cytomegalovirus promoter.

Altered cytokine export and apoptosis in mice deficient in interleukin-1 beta converting enzyme.

The interleukin-1 beta (IL-1 beta) converting enzyme (ICE) processes the inactive IL-1 beta precursor to the proinflammatory cytokine. Adherent monocytes from mice harboring a disrupted ICE gene (ICE-/-) did not export IL-1 beta or interleukin-1 alpha (IL-1 alpha) after stimulation with lipopolysaccharide. Export of tumor necrosis factor-alpha and interleukin-6 (IL-6) from these cells was also diminished. Thymocytes from ICE-/- mice were sensitive to apoptosis induced by dexamethasone or ionizing radiation, but were resistant to apoptosis induced by Fas antibody. Despite this defect in apoptosis, ICE-/- mice proceed normally through development.

Activation of interferon-gamma inducing factor mediated by interleukin-1beta converting enzyme.

The interleukin-1beta (IL-1beta) converting enzyme (ICE) processes the inactive IL-1beta precursor to the proinflammatory cytokine. ICE was also shown to cleave the precursor of interferon-gamma inducing factor (IGIF) at the authentic processing site with high efficiency, thereby activating IGIF and facilitating its export. Lipopolysaccharide-activated ICE-deficient (ICE-/-) Kupffer cells synthesized the IGIF precursor but failed to process it into the active form. Interferon-gamma and IGIF were diminished in the sera of ICE-/- mice exposed to Propionibacterium acnes and lipopolysaccharide. The lack of multiple proinflammatory cytokines in ICE-/- mice may account for their protection from septic shock.

Interleukin-18 (IFNgamma-inducing factor) induces IL-8 and IL-1beta via TNFalpha production from non-CD14+ human blood mononuclear cells.

IL-18 is synthesized as a precursor molecule without a signal peptide but requires the IL-1beta converting enzyme (ICE, caspase-1) for cleavage into a mature peptide. Human precursor IL-18 was expressed, purified, and cleaved by ICE into a 18-kD mature form. Mature IL-18 induced IL-8, macrophage inflammatory protein-1alpha, and monocyte chemotactic protein-1 in human peripheral blood mononuclear cells in the absence of any co-stimuli. Blocking IL-1 with IL-1 receptor antagonist resulted in a 50% reduction in IL-8. Neutralization of TNF with TNF binding protein resulted in a 66% reduction in IL-1beta, an 80% reduction of IL-8, and an 88% reduction in mean TNFalpha mRNA. In purified CD14+ cells but not CD3+/CD4+, IL-18 induced gene expression and synthesis of IL-8 and IL-1beta. TNFalpha production was induced in the non-CD14+ population and there was no induction of TNFbeta by IL-18. In purified natural killer cells, IL-18 induced IL-8 that was also inhibited by TNF binding protein. IL-18 did not induce antiinflammatory cytokines, IL-1Ra, or IL-10, although IL-18 induction of TNFalpha was inhibited by IL-10. In the presence of IFNgamma, IL-18-induced TNFalpha was enhanced and there was an increase in the mature form of IL-1beta. We conclude that IL-18 possesses proinflammatory properties by direct stimulation of gene expression and synthesis of TNFalpha from CD3+/CD4+ and natural killer cells with subsequent production of IL-1beta and IL-8 from the CD14+ population.

Role of p38 and JNK mitogen-activated protein kinases in the activation of ternary complex factors.

The transcription factors Elk-1 and SAP-1 bind together with serum response factor to the serum response element present in the c-fos promoter and mediate increased gene expression. The ERK, JNK, and p38 groups of mitogen-activated protein (MAP) kinases phosphorylate and activate Elk-1 in response to a variety of extracellular stimuli. In contrast, SAP-1 is activated by ERK and p38 MAP kinases but not by JNK. The proinflammatory cytokine interleukin-1 (IL-1) activates JNK and p38 MAP kinases and induces the transcriptional activity of Elk-1 and SAP-1. These effects of IL-1 appear to be mediated by Rho family GTPases. To examine the relative roles of the JNK and p38 MAP kinase pathways, we examined the effects of IL-1 on CHO and NIH 3T3 cells. Studies of NIH 3T3 cells demonstrated that both the JNK and p38 MAP kinases are required for IL-1-stimulated Elk-1 transcriptional activity, while only p38 MAP kinase contributes to IL-1-induced activation of SAP-1. In contrast, studies of CHO cells demonstrated that JNK (but not the p38 MAP kinase) is required for IL-1-stimulated Elk-1-dependent gene expression and that neither JNK nor p38 MAP kinase is required for IL-1 signaling to SAP-1. We conclude that (i) distinct MAP kinase signal transduction pathways mediate IL-1 signaling to ternary complex transcription factors (TCFs) in different cell types and (ii) individual TCFs show different responses to the JNK and p38 signaling pathways. The differential utilization of TCF proteins and MAP kinase signaling pathways represents a potential mechanism for the determination of cell-type-specific responses to extracellular stimuli.

Crystal structure of JNK3: a kinase implicated in neuronal apoptosis.

BACKGROUND: The c-Jun N-terminal kinases (JNKs) are members of the mitogen-activated protein (MAP) kinase family, and regulate signal transduction in response to environmental stress. Activation and nuclear localization of JNK3, a neuronal-specific isoform of JNK, has been associated with hypoxic and ischemic damage of CA1 neurons in the hippocampus. Knockout mice lacking JNK3 showed reduced apoptosis of hippocampal neurons and reduced seizure induced by kainic acid, a glutamate-receptor agonist. Thus, JNK3 may be important in the pathology of neurological disorders and is of significant medical interest. RESULTS: We report here the structure of unphosphorylated JNK3 in complex with adenylyl imidodiphosphate, an ATP analog. JNK3 has a typical kinase fold, with the ATP-binding site situated within a cleft between the N- and C-terminal domains. In contrast to other known MAP kinase structures, the ATP-binding site of JNK3 is well ordered; the glycine-rich nucleotide-binding sequence forms a beta-strand-turn-beta-strand structure over the nucleotide. Unphosphorylated JNK3 assumes an open conformation, in which the N- and C-terminal domains are twisted apart relative to their positions in cAMP-dependent protein kinase. The rotation leads to the misalignment of some of the catalytic residues. The phosphorylation lip of JNK3 partially blocks the substrate-binding site. CONCLUSIONS: This is the first JNK structure to be determined, providing a unique opportunity to compare structures from the three MAP kinase subfamilies. The structure reveals atomic-level details of the shape of JNK3 and the interactions between the kinase and the nucleotide. The misalignment of catalytic residues and occlusion of the active site by the phosphorylation lip may account for the low activity of unphosphorylated JNK3. The structure provides a framework for understanding the substrate specificity of different JNK isoforms, and should aid the design of selective JNK3 inhibitors.

High levels of expression and nuclear localization of interleukin-1 beta converting enzyme (ICE) and CPP32 in favorable human neuroblastomas.

Neuroblastomas frequently show spontaneous regression and differentiation, which may at least partly be regulated by signaling through nerve growth factor and its receptors, TRK-A and p75LNTR. We studied 52 neuroblastic tumors to test whether the cell death-related proteases, interleukin-1 beta converting enzyme (ICE), CPP32, and Ich-1, were involved in the regression of the tumors. High levels of expression of ICE and CPP32 were significantly correlated with a high level of TRK-A expression, single copy of N-myc, younger age, lower stages, and better prognosis. The immunohistochemical studies and Western analyses as well as the terminal dUTP-biotin nick end labeling (TUNEL) method revealed that both ICE and CPP32 were translocated from the cytoplasm into the nuclei in regressing, apoptotic tumor cells. Our results suggest that ICE and CPP32 cysteine proteases may play an important role in regulating the apoptotic process of the favorable neuroblastomas.

The structural basis for the specificity of pyridinylimidazole inhibitors of p38 MAP kinase.

BACKGROUND: The p38 mitogen-activated protein (MAP) kinase regulates signal transduction in response to environmental stress. Pyridinylimidazole compounds are specific inhibitors of p38 MAP kinase that block the production of the cytokines interleukin-1beta and tumor necrosis factor alpha, and they are effective in animal models of arthritis, bone resorption and endotoxin shock. These compounds have been useful probes for studying the physiological functions of the p38-mediated MAP kinase pathway. RESULTS: We report the crystal structure of a novel pyridinylimidazole compound complexed with p38 MAP kinase, and we demonstrate that this compound binds to the same site on the kinase as does ATP. Mutagenesis showed that a single residue difference between p38 MAP kinase and other MAP kinases is sufficient to confer selectivity among pyridinylimidazole compounds. CONCLUSIONS: Our results reveal how pyridinylimidazole compounds are potent and selective inhibitors of p38 MAP kinase but not other MAP kinases. It should now be possible to design other specific inhibitors of activated p38 MAP kinase using the structure of the nonphosphorylated enzyme.

Dynamic NMR studies of ligand-receptor interactions: design and analysis of a rapidly exchanging complex of FKBP-12/FK506 with a 24 kDa calcineurin fragment.

Dynamic NMR methods, such as differential line broadening and transferred NOE spectroscopy, are normally reserved for the study of small molecule ligand interactions with large protein receptors. Using a combination of isotope labeling and isotope edited NMR, we have extended these techniques to characterize interactions of a much larger protein/drug complex, FKBP-12/ FK506 with its receptor protein, calcineurin. In order to examine this multicomponent system by dynamic NMR methods, the 93 kDa, tightly bound FKBP-12/FK506/Cn complex was replaced with a lower affinity, rapidly exchanging system consisting of FKBP-12/FK506 (13 kDa), recombinant calcineurin subunit B (CnB) (20 kDa), and a synthetic peptide (4 kDa) corresponding to the B binding domain (BBD) of calcineurin catalytic subunit A (CnA). Analysis of 1H-13C HSQC data acquired for the FKBP-12/ 13C-FK506 and FKBP-12/13C-FK506/CnB/BBD complexes indicates that FKBP-12/FK506 and CnB/BBD are in fast exchange in the quaternary complex. Comparison of proton line widths shows significant broadening of resonances along the macrocycle backbone at 13-CH, 13-OMe, 15-OMe, 18-CH2, 20-CH, 21-CH, and 25-Me, as well as moderate broadening on the macrocycle backbone at 17-Me, 24-CH, and the pyranose 12-CH2 protons. The tri-substituted olefin and cyclohexyl groups also show moderate broadening at the 27-Me, 28-CH, and 30-CH2 positions, respectively. Unexpectedly, little line broadening was observed for the allyl resonances of FK506 in the quaternary complex, although 13C longitudinal relaxation measurements suggest this group also makes contacts with calcineurin. In addition, intermolecular transfer NOE peaks were observed for the allyl 37-CH2, 21-CH, 30-CH2, 13-OMe, 15-OMe, 17-Me, 25-Me, and 27-Me groups, indicating that these are potential sites on the FK506 molecule that interact with calcineurin.

A single amino acid substitution makes ERK2 susceptible to pyridinyl imidazole inhibitors of p38 MAP kinase.

Mitogen-activated protein (MAP) kinases are serine/threonine kinases that mediate intracellular signal transduction pathways. Pyridinyl imidazole compounds block pro-inflammatory cytokine production and are specific p38 kinase inhibitors. ERK2 is related to p38 in sequence and structure, but is not inhibited by pyridinyl imidazole inhibitors. Crystal structures of two pyridinyl imidazoles complexed with p38 revealed these compounds bind in the ATP site. Mutagenesis data suggested a single residue difference at threonine 106 between p38 and other MAP kinases is sufficient to confer selectivity of pyridinyl imidazoles. We have changed the equivalent residue in human ERK2, Q105, into threonine and alanine, and substituted four additional ATP binding site residues. The single residue change Q105A in ERK2 enhances the binding of SB202190 at least 25,000-fold compared to wild-type ERK2. We report enzymatic analyses of wild-type ERK2 and the mutant proteins, and the crystal structure of a pyridinyl imidazole, SB203580, bound to an ERK2 pentamutant, I103L, Q105T, D106H, E109G. T110A. These ATP binding site substitutions induce low nanomolar sensitivity to pyridinyl imidazoles. Furthermore, we identified 5-iodotubercidin as a potent ERK2 inhibitor, which may help reveal the role of ERK2 in cell proliferation.

Kinetic mechanism and ATP-binding site reactivity of p38gamma MAP kinase.

Activated p38gamma MAP kinase exhibited significant basal ATPase activity in the absence of a kinase substrate, and addition of a phosphoacceptor substrate increased k(cat)/K(m)20-fold. AMP-PCP was competitive with ATP binding and non-competitive with phosphoacceptor substrate binding. The nucleotide binding site affinity label 5'-(p-fluorosulfonylbenzoyl)adenosine (FSBA) bound stoichiometrically at Lys-56 in the ATP site of both unphosphorylated and activated p38gamma. AMP-PCP only protected the activated enzyme from FSBA inactivation, implying that AMP-PCP does not bind unphosphorylated p38gamma. Basal ATPase activities were also observed for activated p38alpha, ERK2 and JNK3 suggesting that the enzymatic mechanism may be similar for all classes of MAP kinases.

Aprosodia in Chinese patients with right cerebral hemisphere lesions.

Recent publications, all involving native speakers of English, have established that lesions in the right cerebral hemisphere produce a deficit in the comprehension and execution of tonal change in language related to the affective component of prosody. We tested 12 Chinese patients with right-hemisphere lesions and seven controls for comprehension, discrimination, repetition, and expression of prosody and gesture. In 11 of the 12 patients, aprosodia was identified. The subjects were also tested for their ability to detect semantic tonal difference in Chinese. Only five of the 12 showed a mild deficit in this task, suggesting that the left cerebral hemisphere is more dominant for comprehension of tone essential to word meaning.

Inhibitors of p38 MAP kinase: therapeutic intervention in cytokine-mediated diseases.

p38 MAP kinase is a member of the family of kinases which mediate intracellular transduction pathways. The activation of this particular MAP kinase pathway is in response to a broad variety of extracellular stimuli. Subsequent downstream events triggered by p38 activation result in the production of IL-1 and TNF-a, suggesting that inhibition of this enzyme may provide a useful therapeutic target for intervention in various diseases mediated by these cytokines. Understanding the biological consequences of p38 activation and inhibition has been the subject of intensive research over the past several years and there is now ample evidence to suggest that inhibition of this enzyme represents a valid approach for target intervention in various cytokine-mediated diseases. Crystal structures of both apo enzyme and enzyme bound to various ligands in conjunction with site specific mutagenesis studies have provided a wealth of information regarding the interactions necessary to result in potent inhibition and selectivity from other kinases. This information has proven useful towards the analysis of previously reported compounds and will provide additional insight towards the design of new compounds and building upon existing SAR.

Relationship between mesial temporal seizure focus and elevated serum prolactin in temporal lobe epilepsy.

We evaluated the relationship between mesial temporal seizure focus and serum prolactin (PRL) in patients before and after they underwent anterior temporal lobectomy (ATL) for medically intractable temporal lobe epilepsy (TLE). These patients had a confirmed unilateral epileptogenic focus in mesial temporal structures, a postictal rise in serum PRL 15 to 20 minutes after onset of complex partial seizures, and were refractory for more than 2 years to antiepileptic drugs. Presurgical interictal serum PRL levels were significantly elevated (16.47 +/- 0.85 ng/mL, n = 62) and declined after ATL to normal values (patients, 9.63 +/- 0.55 ng/mL, n = 54; normal subjects, 8.99 +/- 0.57 ng/mL, n = 52). Serial evaluations indicated that normalization was seen 3 months after surgery (9.42 +/- 1.22 ng/mL, n = 9). The postsurgical reduction in serum PRL was similar in men and women, in patients with epileptogenic focus on either side of mesial temporal structures, and was unaffected by antiepileptic medication. We conclude that PRL is elevated following seizures and that a seizure focus in mesial temporal structures may exert a sustained excitatory influence on PRL release in patients with medically intractable TLE.

Transient elevation in plasma prolactin level in rats with temporal lobe status epilepticus.

Microinjection of kainic acid into the CA3 subfield of hippocampus in anesthetized rats elicited seizure-like hippocampal EEG activity that persisted for more than 180 minutes. There was a concomitant rise in plasma prolactin level that peaked at 15 to 20 minutes but endured less than 60 minutes. We conclude that plasma prolactin exhibited only transient elevations during experimental temporal lobe status epilepticus in rats.

Interleukin-1 beta converting enzyme (ICE) is preferentially expressed in neuroblastomas with favourable prognosis.

To determine whether interleukin-1 beta converting enzyme (ICE) plays a role in the programmed cell death of neuroblastoma, we studied ICE expression in primary tumours. In patients in stages I, II and IVS, ICE mRNA was detected in 22 of 32 (69%) tumours, while only 5 of 26 (19%) tumours expressed ICE in stages III and IV (P < 0.001). ICE mRNA was expressed in 27 of 47 (57%) tumours without MYCN amplification, but it was not detected in any tumours with MYCN amplification (P < 0.01). Immunohistochemically, the cytoplasm was stained in all 15 neuroblastomas examined. The nuclei were stained in 12 neuroblastomas without MYCN amplification, whereas only 1 of 3 tumours with MYCN amplification had positive staining in the nuclei. In ganglioneuromas, high levels of ICE mRNA were expressed, but immunostaining showed that the protease expression was confined to the cytoplasm. These observations suggest that ICE may be associated with the spontaneous regression often seen in favourable neuroblastomas and that localisation of ICE protease in the cell may be important for the cell death pathway. Double staining for ICE and TUNEL showed that they were co-localised in some nuclei, but the distribution of ICE protease expression was not necessarily the same as that of DNA fragmentation, suggesting that the protease expression probably preceded DNA fragmentation during the apoptotic process. ICE may play an important role in regulating the apoptotic process of neuroblastoma.

Unusual electroencephalographic findings in subacute sclerosing panencephalitis: a case report.

Subacute sclerosing panencephalitis (SSPE) is a rare infectious central nervous system (CNS) disease with a poor prognosis. We reported on the case of an adolescent girl with SSPE and characteristic periodic electroencephalographic (EEG) complexes. Her neurological deficits including generalized myoclonic seizures improved after intraventricular interferon (IFN) treatment. However, unusual EEG patterns consisting of bisynchronous occipital spikes preceding periodic complexes developed in follow-up EEGs.

Performance of WSSV-infected and WSSV-negative Penaeus monodon postlarvae in culture ponds.

In a survey of 27 Penaeus monodon culture ponds stocked with postlarvae (approximately PL10) at medium density (approximately 40 shrimp m(-2)), single-step nested white spot syndrome virus (WSSV) PCR was used to measure the WSSV infection rates in the shrimp populations within 1 mo after stocking. Seven ponds were initially WSSV-free, and the shrimp in 5 of these were harvested successfully. In the ponds (n = 6) where detection rates were higher than 50%, mass mortality occurred during the growth period, and none of these ponds was harvested successfully. In a subsequent study, P. monodon brooders were classified into 3 groups according to their WSSV infection status before and after spawning: brooders that were WSSV-positive before spawning were assigned to group A; spawners that became WSSV-positive only after spawning were assigned to group B; and group C consisted of brooders that were still WSSV-negative after spawning. WSSV screening showed that 75, 44 and 14%, respectively, of group A, B and C brooders produced nauplii that were WSSV-positive. Most (57%; 16/28) of the brooders in group A produced nauplii in which the WSSV prevalence was high (>50%). When a pond was stocked with high-prevalence nauplii from 1 of these group A brooders, an outbreak of white spot syndrome occurred within 3 wk and only approximately 20% of the initial population survived through to harvest (after 174 d). By contrast, 2 other ponds stocked with low-prevalence and WSSV-negative nauplii (derived respectively from 2 brooders in group B), both had much higher survival rates (70 to 80%) and yielded much larger (approximately 3x by weight) total harvests. We conclude that testing the nauplii is an effective and practical screening strategy for commercially cultured P. monodon.