Biomedical subjects

Y Aihara

Publications and source records attributed to Y Aihara.

At least 37 records · Page 2Linked to original sources

PubMed2001

Quantitative analysis of gene expressions related to inflammation in canine spastic artery after subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: The possible role of inflammatory reaction of the cerebral artery in the pathogenesis of cerebral vasospasm has been noted in recent studies. We quantitatively measured the levels of expression of genes related to inflammation in the spastic artery in a canine double-hemorrhage model. METHODS: Twenty dogs were assigned to 4 groups: group D0, control; group D2, dogs killed 2 days after cisternal injection of blood; group D7, dogs given double cisternal injections of blood and killed 7 days after the first injection; and group D14. Angiography was performed twice: on the first day and before the animals were killed. Total RNA was extracted from the basilar artery. The expressions of interleukin (IL)-1alpha, IL-6, IL-8, IL-10, tumor necrosis factor-alpha, E-secretin, fibronectin, intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule-1, transforming growth factor-ss, basic fibroblast growth factor, and collagen types I, III, and IV were examined with TaqMan real-time quantitative reverse transcription-polymerase chain reaction. RESULTS: Prolonged arterial narrowing peaking on 7 day was observed. There was a significant difference in vessel caliber between D0, D2, D7, and D14 groups (P:<0.0001). There were significant differences in mRNA expression in the basilar artery for IL-1alpha, IL-6, IL-8, ICAM-1, and collagen type I between D0, D2, D7, and D14 groups (P:=0.0079, 0. 0196, 0.0040, 0.0017, and <0.0001, respectively). The average level of mRNA was highest in D7 for IL-1alpha, IL-6, IL-8, and ICAM-1 (17-, 16-, 131-, and 1.7-fold compared with those of D0, respectively) and in D14 for collagen type I (10.9-fold). CONCLUSIONS: Increased expression of genes related to inflammation in the spastic artery suggests that inflammatory reaction of the cerebral artery is associated with sustained contraction.

Animals↗

PubMed2001

[Three elderly cases of hyperostosis cranii with various clinical symptoms].

We report three elderly patients with hyperostosis cranii (HC). Patient 1 had two episodes of unconsciousness; patient 2, headache; and patient 3, dementia. On the basis of the classification of Moore using skull films, patients 1 and 2 showed hyperostosis frontoparietalis and patient 3 had hyperostosis frontalis interna. Electroencephalography showed transient generalized spike and slow wave complexes over the frontal lobes in patient 1. Magnetic resonance (MR) images showed frontal lobes compressed by the thickness of the frontal bones in all patients and thickened parietal bones in patients 1 and 2. Because findings in our series and in the literature suggest that HC may show unexpected neuropsychiatric symptoms, HC should be checked in elderly patients whose presenting symptoms include epilepsy, dementia, psychiatric disease, headache and so on. MR images should reveal the relationship between clinical symptoms and the deformation of brains by the skull.

Aged↗

PubMed2001

Immunoscintigraphy of aortic dissection with 99mTc-labeled murine anti-smooth muscle myosin monoclonal antibody in rats.

UNLABELLED: Aortic dissection is among the most common of fatal conditions of the aorta. Prompt and accurate diagnosis of the site and extent of the lesion is necessary for adequate therapy. However, this catastrophic disease, characterized by extensive damage to smooth muscle cells, lacks specific signs and symptoms. As a result, the diagnosis is still frequently missed today and a new diagnostic method to specifically identify aortic dissection would be attractive. The purpose of this study was to examine the feasibility of radioimmunoscintigraphy using 99mTc-anti-smooth muscle myosin monoclonal antibody (SM-MAb) for the noninvasive diagnosis of aortic dissection in the rat experimental model. METHODS: The accumulation of 99mTc-anti-SM-MAb was studied, and scintigraphic imaging with 99mTc-anti-SMMAb was performed in rats immediately after experimental aortic dissection and 1 and 2 wk later. RESULTS: The radioactivity of 99mTc-anti-SM-MAb in the dissected aorta showed a significant increase compared both with the normal portion of the aorta and with blood 6 h after injection of the radiotracer; the ratio of the percentage injected dose per gram (%lD/g) in the lesion to that retained in the normal portion was 4.17 +/- 1.47. Scintigraphic imaging with 99mTc-anti-SM-MAb allowed distinct visualization of the dissected aorta with specific accumulation of antibody 6 h after tracer injection. Selective accumulation of the tracer in the dissected portion of the aorta persisted even 1 wk after aortic injury, allowing clear visualization of the dissected lesion by scintigraphy. CONCLUSION: Radioimmunoscintigraphy using anti-SM-MAb is a potentially useful noninvasive diagnostic method for imaging aortic dissection.

Aortic Dissection↗

PubMed2000

Alteration in dopamine metabolism in the thermoregulatory center of exercising rats.

To examine the role of monoamines and amino acids in thermoregulation, we measured their concentrations in the preoptic area and anterior hypothalamus (PO/AH) in exercising rats, using an in vivo microdialysis technique. Body temperature (Tb) was monitored using a telemetry system. Tb increase by about 1.0 degrees C in the first 15 min of treadmill exercise (10 m/min; for 60 min), and was maintained thereafter at a steady high level possibly due to activation of the heat loss system. The levels of dopamine metabolites (3,4-dihydroxyphenylacetic acid and homovanillic acid) in the PO/AH significantly increased during exercise. However, exercise did not induce an increase in the level of either serotonergic substances (5-hydroxytryptamine and 5-hydroxyindoleacetic acid) or amino acids (aspartate and glutamate). Our data indicate that dopamine breakdown processes in the PO/AH are activated during exercise. Dopamine in the PO/AH may be involved in the heat loss mechanisms for thermoregulation when Tb rises during exercise.

Animals↗

PubMed2000

Effects of ambient light on body temperature regulation in resting and exercising rats.

We investigated the effects of environmental light and darkness on thermoregulation during both daytime and nighttime by monitoring body temperature (T(b)) and physical activity of rats using a telemetry system. Experiments were performed in both resting and exercising rats. In resting rats, lights-off during the daytime resulted in an increase in both T(b) and activity. Conversely, during the nighttime, T(b) decreased with the lights-on stimulus despite the fact that the activity was left unchanged. Treadmill exercise (10 m/min) always increased T(b) from the basal resting level. In both daytime and nighttime, exercising rats exhibited a persistent T(b)-rise when lights were on. However, in the lights-off condition at nighttime, the T(b) of exercising rats increased to a level significantly higher than that of exercising rats with the lights-on. Our results suggest that light at nighttime causes the suppression of T(b) in both resting and exercising rats.

Animals↗

PubMed2000

Doxorubicin represses CARP gene transcription through the generation of oxidative stress in neonatal rat cardiac myocytes: possible role of serine/threonine kinase-dependent pathways.

Doxorubicin (Dox), an anthracyclin antineoplastic agent, causes dilated cardiomyopathy. CARP has been identified as a nuclear protein whose mRNA levels are exquisitely sensitive to Dox. In this study we investigated the molecular mechanisms underlying the repression of CARP expression by Dox in cultured neonatal rat cardiac myocytes. Dox (1 micromol/l)-mediated decrease in CARP mRNA levels was strongly correlated with BNP but not with ANP mRNA levels. Hydrogen peroxide scavenger catalase (1 mg/ml) but not hydroxyl radical scavengers dimethylthiourea (10 mmol/l) or mannitol (10 mmol/l) blunted the Dox-mediated decrease in CARP and BNP expression. Superoxide dismutase inhibitor diethyldithiocarbamic acid (10 mmol/l), which inhibits the generation of hydrogen peroxide from superoxide metabolism, attenuated the repression. PD98059 (MEK1 inhibitor, 50 micromol/l), SB203580 (p38 MAP kinase inhibitor, 10 micromol/l), calphostin C (protein kinase C (PKC) inhibitor, 1 micromol/l), non-selective protein tyrosine kinase inhibitors genistein (50 micromol/l) or herbimycin A (1 micromol/l) failed to abrogate the downregulation of CARP and BNP expression by Dox. In contrast, H7 (30 micromol/l), a potent inhibitor of serine/threonine kinase, significantly blocked Dox-mediated downregulation of CARP and BNP expression. Transient transfection of a series of 5'-deletion and site-specific mutation constructs revealed that M-CAT element located at -37 of the human CARP promoter mediates Dox-induced repression of CARP promoter activity. These results suggest that a genetic response to Dox is mediated through the generation of hydrogen peroxide, which is selectively linked to the activation of H7-sensitive serine/threonine kinase distinct from PKC and well characterized mitogen-activated protein (MAP) kinases (ERK and p38MAP kinase). Furthermore, our data implicated M-CAT element as a Dox-response element within the CARP promoter in cardiac myocytes.

Animals↗

PubMed2000

Induction of VEGF gene transcription by IL-1 beta is mediated through stress-activated MAP kinases and Sp1 sites in cardiac myocytes.

Interleukin-1 beta (IL-1 beta) is a multipotent cytokine participating in a variety of cardiovascular diseases. In this study, we examined the effects of IL-1 beta on the expression of vascular endothelial cell growth factor (VEGF) and pursued the molecular mechanisms underlying this effect. Treatment of cultured neonatal rat cardiac myocytes with IL-1 beta increased the levels of VEGF mRNA in a time- and a concentration-dependent manner. These effects were completely abolished by SB203580 and SB202190 (p38 MAPK inhibitors) but not by PD98059 (MEK1 inhibitor), calphostin C (protein kinase C inhibitor), or genistein (tyrosine kinase inhibitor). While IL-1 beta phosphorylated c-Jun N-terminus protein kinase (JNK) rapidly and transiently, the effect of IL-1 beta on p38 mitogen-activated protein kinase (MAPK) was gradual and persistent. Transient transfection assays showed that IL-1 beta increases the transcription from the VEGF promoter. A series of 5;-deletion and site-specific mutation analyses indicated that IL-1 beta as well as overexpression of p38 MAPK and JNK activate VEGF promoter activity through two G+C-rich sequences located at -73 and -62. Electrophoretic mobility shift and supershift assays showed Sp1 and Sp3 proteins specifically bind to the G+C-rich sequences. The half-life of VEGF mRNA was significantly increased in cells treated with IL-1 beta. Together, these results indicate that IL-1 beta induces VEGF gene expression at both transcriptional and post-transcriptional levels, and IL-1 beta evokes p38 MAPK and JNK signalings, which in turn stimulate the transcription of the VEGF gene through Sp1-binding sites. These findings suggest the role of IL-1 beta as a cytokine inducing VEGF in cardiac myocytes, and imply that activation of stress-activated MAP kinases regulate Sp1 sites-dependent transcription.

Animals↗

PubMed2000

Cloning of cDNA and the gene encoding human hepatocyte nuclear factor (HNF)-3 beta and mutation screening in Japanese subjects with maturity-onset diabetes of the young.

AIMS/HYPOTHESIS: Molecular defects of the genes for transcription factors, hepatocyte nuclear factor (HNF)-4 alpha, HNF-1 alpha, HNF-1 beta and insulin promoter factor-1 cause maturity-onset diabetes of the young (MODY1, 3, 5, and 4, respectively). This suggests the HNF-related transcription cascade is important in insulin secretion which is induced by glucose. These genes and the gene encoding glycolytic enzyme glucokinase (MODY2) are, however, responsible for only 15-20% of cases of MODY in the Japanese. Searching for a novel form of MODY in this population, we cloned a new candidate gene encoding human HNF-3 beta, a winged helix transcription factor, which also belongs to the same HNF-transcription cascade. METHODS: The cDNA clone for human HNF-3 beta was isolated from a liver cDNA library. The gene was also cloned from a genomic library and its organization and chromosomal localization were determined. We screened 68 Japanese subjects with MODY/early-onset diabetes for mutations in this gene. RESULTS: Human HNF-3 beta is composed of 457 amino acids. The human gene, which was mapped to the segment 30 cR from SHGC-37039 on chromosome 20p by radiation hybrid mapping, spans approximately 4.5 kb and consists of three exons. Direct sequencing of the exons and flanking regions identified one missense mutation A328 V and seven polymorphisms, although the functional significance of the mutation in the pathogenesis of diabetes is not known. CONCLUSION/INTERPRETATION: The characterization of the structure of the HNF-3 beta gene and its mapping in the framework of markers will be helpful in genetic studies of the various forms of diabetes mellitus.

Amino Acid Sequence↗

PubMed2000

Usefulness of serum fibrinogen degradation product-E in sporadic cases of classical hemolytic uremic syndrome.

BACKGROUND: Hemolytic uremic syndrome (HUS) associated with Shiga toxin (Stx)-producing Escherichia coli O157:H7 infection is one of the diseases causing acute renal failure in young children. Although HUS is still a serious disease in children, no reliable predictive markers for HUS nor markers of disease severity are available so far. Recently, we experienced a sporadic case of typical HUS caused by Stx-producing E. coli O157:H7 and detected, at the prodromal stage, a high level of serum fibrin/fibrinogen degradation product-E (FDP-E) fraction. METHODS: To assess the usefulness of FDP-E for the treatment of HUS in clinical practice, we retrospectively examined serum levels of FDP-E in 22 patients with bloody diarrhea with or without HUS. RESULTS: There were significantly increased levels of serum FDP-E in patients with HUS, but not in those without HUS. Furthermore, serum levels of FDP-E may correlate with disease severity in patients with HUS. CONCLUSIONS: These results suggest that serum levels of FDP-E may be a useful marker of HUS in clinical practice.

Biomarkers↗

PubMed2000

Molecular cloning of a novel brain-type Na(+)-dependent inorganic phosphate cotransporter.

We have isolated a human cDNA encoding a protein, designated DNPI, that shows 82% amino acid identity and 92% similarity to the human brain-specific Na(+)-dependent inorganic phosphate (Na(+)/P(i)) cotransporter (BNPI), which is localized exclusively to neuron-rich regions. Expression of DNPI mRNA in Xenopus oocytes resulted in a significant increase in Na(+)-dependent P(i) transport, indicating that DNPI is a novel Na(+)/P(i) cotransporter. Northern blot analysis shows that DNPI mRNA is expressed predominantly in brain, where the highest levels are observed in medulla, substantia nigra, subthalamic nucleus, and thalamus, all of which express BNPI mRNA at low levels. In contrast, DNPI mRNA is expressed at low levels in cerebellum and hippocampus, where BNPI mRNA is expressed at high levels. No hybridizing signal for DNPI mRNA is observed in the glia-rich region of corpus callosum. In other regions examined, both mRNAs are moderately or highly expressed. These results indicate that BNPI and DNPI, which coordinate Na(+)-dependent P(i) transport in the neuron-rich regions of the brain, may form a new class within the Na(+)/P(i) cotransporter family.

Animals↗

PubMed2000

Influence of vibration to the neck, trunk and lower extremity muscles on equilibrium in normal subjects and patients with unilateral labyrinthine dysfunction.

To investigate the role of proprioceptors of different skeletal muscles in postural control, in normal subjects and patients with unilateral labyrinthine dysfunction (ULD), the effect of vibration on these muscles was studied by postulography. The subjects comprised 59 normal subjects and 12 patients with ULD due to resection of acoustic tumours. Sagittal body sway was observed during vibration to the triceps surae, tibialis anterior and upper dorsal neck muscles. No significant change in sway was observed in the frontal plane in normal subjects. Significant differences between normal subjects and patients were found on stimulation of the muscle groups of triceps surae and biceps femoris during vibration. In patients with ULD, vibration to the dorsal neck muscles caused a deviation towards the diseased side. It can be speculated that the upper dorsal neck muscle plays an important role in maintaining the body balance in the frontal plane in patients with ULD. On the other hand, the lower extremity muscles, especially the muscles on the dorsal side of the body, play a significant role in adjusting the standing posture in the sagittal plane.

Adult↗

PubMed2000

[Why there were few isolations of tubercle bacilli in young children with pulmonary tuberculosis?].

We retrospectively evaluated the factors influencing the isolation of tubercle bacilli in 51 children under 14 years of age with pulmonary tuberculosis who were admitted to Yokohama City University Hospital from 1975 to 1998. Young children (0-6 years of age) with pulmonary tuberculosis were significantly less positive by smear and culture than elder children (7-14 years of age) with pulmonary tuberculosis. According to the Japanese Society for Tuberculosis classification of finding on chest X-ray film for pulmonary tuberculosis, the culture-positive patients with type II (cavitary lesions) were found in all, the culture-positive patients with type III (non-cavitary lesions) in 39.3%, and the culture-positive patients with type H (hilar and mediastinal lymphadenopathys) in 35.3%. Patients with cavitary lesions (type II) were significantly more positive by smear and culture than patients with non-cavitary lesions (type III + type H). Only 15.8% of the young children with pulmonary tuberculosis had received BCG vaccine and all had non-cavitary lesions (type III and type H). But, 84.6% out of the older children had received BCG vaccine and half had cavitary lesions. Taken together, the result was that there were few isolation of tubercle bacilli in young children with pulmonary tuberculosis because they had non-cavitary tuberculosis without delayed-type hypersensitivity to tubercle bacilli.

Adolescent↗

PubMed2000

Inducible expression of manganese superoxide dismutase by phorbol 12-myristate 13-acetate is mediated by Sp1 in endothelial cells.

The expression of manganese superoxide dismutase (Mn-SOD), an important component of the cellular defense system against oxidative stress, is induced in response to a variety of stimuli, including cytokines and phorbol esters, in endothelial cells. To define the molecular mechanisms regulating the expression of Mn-SOD, we have characterized the promoter of the human Mn-SOD gene. In calf pulmonary artery endothelial cells, phorbol 12-myristate 13-acetate (PMA) gradually increased Mn-SOD mRNA levels, with a peak at 6 to 12 hours after stimulation. The increase in Mn-SOD mRNA was significantly inhibited by a protein kinase C (PKC) inhibitor (calphostin C) but not by a mitogen-activated protein kinase kinase-1 inhibitor (PD98059) or a p38 mitogen-activated protein kinase inhibitor (SB203580). By reporter gene transfection experiments of a series of promoter deletions and site-directed mutation constructs, we found 2 consensus Sp1 binding sequences located at -97 and at -77 to play an important role in PMA-induced Mn-SOD transcription. Electrophoretic gel mobility shift assays have indicated that this sequence serves as an Sp1 binding site. Northern and Western blot analysis has revealed that PMA-induced promoter activity of Mn-SOD correlates with an increased expression of Sp1. Nuclear proteins from PMA-treated calf pulmonary artery endothelial cells displayed an increased DNA binding to the Sp1 site. Furthermore, the Mn-SOD promoter was activated either by overexpression of Sp1 or the constitutively activated form of PKCbeta in an Sp1 site-dependent manner. These results suggest that PMA stimulates transcription of the Mn-SOD gene through an increase in Sp1 expression and thus implicate Sp1 as an effector mediating the PKC-signaling pathway elicited by extracellular signals.

Animals↗

PubMed2000

Cardiac ankyrin repeat protein is a novel marker of cardiac hypertrophy: role of M-CAT element within the promoter.

CARP, a cardiac doxorubicin (adriamycin)-responsive protein, has been identified as a nuclear protein whose expression is downregulated in response to doxorubicin. In the present study, we tested the hypothesis that CARP serves as a reliable genetic marker of cardiac hypertrophy in vivo and in vitro. CARP expression was markedly increased in 3 distinct models of cardiac hypertrophy in rats: constriction of abdominal aorta, spontaneously hypertensive rats, and Dahl salt-sensitive rats. In addition, we found that CARP mRNA levels correlate very strongly with the brain natriuretic peptide mRNA levels in Dahl rats. Transient transfection assays into primary cultures of neonatal rat cardiac myocytes indicate that transcription from the CARP and brain natriuretic peptide promoters is stimulated by overexpression of p38 and Rac1, components of the stress-activated mitogen-activated protein kinase pathways. Mutation analysis and electrophoretic mobility shift assays indicated that the M-CAT element can serve as a binding site for nuclear factors, and this element is important for the induction of CARP promoter activity by p38 and Rac1. Thus, our data suggest that M-CAT element is responsible for the regulation of the CARP gene in response to the activation of stress-responsive mitogen-activated protein kinase pathways. Moreover, given that activation of these pathways is associated with cardiac hypertrophy, we propose that CARP represents a novel genetic marker of cardiac hypertrophy.

Animals↗

PubMed2000

Augmented responses of angiotensin I and II in patients with ischemic heart disease: relation to left ventricular function.

To evaluate the effects of left ventricular (LV) dysfunction upon the sympathetic nervous and renin-aldosterone-angiotensin systems, neurohormonal factors were measured in patients with ischemic heart disease. Eleven patients were divided into two groups by their LV ejection fraction based on previous catheterization; preserved (EF > or = 60%) and impaired (EF < 60%) LV systolic function groups. They performed supine ergometer exercise and blood samples were drawn at rest and at peak exercise. After dynamic exercise, plasma norepinephrine was significantly (p < 0.05) increased in patients with preserved LV function, whereas it was not altered in patients with impaired LV function (norepinephrine 20.8 +/- 20.5 vs 45.8 +/- 41.9, respectively). We observed no differences in basal or peak levels of neurohormonal factors, including plasma renin activity, aldosterone, and brain natriuretic peptide (BNP), between the groups. Although the plasma levels of angiotensin I and II were not different in the two groups at rest or at peak exercise, their increasing ratios from rest to peak exercise were significantly higher in patients with impaired LV function compared to those with preserved LV function (angiotensin I; -18.6 +/- 31.0% vs 64.8 +/- 66.5%, p < 0.05, angiotensin II; -5.9 +/- 41.2% vs 60.7 +/- 40.4% , p < 0.05). These results suggest that the increasing ratios of angiotensin I and II are superior to BNP as predictors of LV dysfunction, and that the sympathetic nervous system has already been activated even at rest and did not respond to dynamic exercise in patients with LV dysfunction in ischemic heart disease.

Aged↗

PubMed2000

[Efficacy of methylprednisolone pulse and mild hypothermia therapies in patients with acute encephalopathy].

Five patients with acute encephalopathy underwent methylprednisolone pulse (mPSL-P), hypothermia and their combination therapies (3 cases, 1 case and 1 case, respectively), with excellent outcome. Two cases with severe brain edema survived. One had severe brain damage as a sequelae. The remaining one recovered well after the combination therapy with mPSL-p and mild hypothermia, despite complete obstruction of the fourth ventricle on the first CT scan; the sequelae, hemiplegia and intelligent disturbance, was only mild. Four patients who received mPSL-P therapy within 6 hours after the onset of CNS symptoms recovered well though one was left with epilepsy. These results indicate that mPSL-P and/or hypothermia therapy will be chosen as the treatment of acute encephalopathy.

Acute Disease↗

PubMed2000

[Two cases of methicillin-resistant Staphylococcus aureus (MRSA) sepsis following craniotomy].

We report here two cases of MRSA sepsis following craniotomy. In case 1, a petroclival meningioma was subtotally removed and lumbar drainage was inserted postoperatively to prevent cerebrospinal fluid leakage. Ventriculo-peritoneal shunt was performed after meningitis was treated with vancomycin and panipenem/betamipron. Two weeks after the procedure, the patient revealed continuous spiking fevers related to MRSA sepsis, which did not improve with vancomycin and arbekacin administration. The focus of infection was found by scintigraphy and CT by 67Ga to be spondylo-diskitis at the level of L2-L3. The lesion was removed and bone from the iliac crest grafted. In case 2, seven days after surgery for multiple meningioma, the patient exhibited spiking fevers and swelling in the left leg. The central venous catheter was removed from the left femoral vein and MRSA was found from blood culture. The patient was treated with arbekacin (200 mg/day). Venous thrombosis diagnosed by CT was treated with heparin. Symptoms related to the infection and laboratory data did not improve because the concentration of arbekacin in the blood did not reach an effective level. The symptoms markedly improved when the dose of arbekacin was doubled (400 mg/day).

Adult↗

PubMed2000

[Effects of mild hypothermia and steroid pulse combination therapy on acute encephalopathy associated with influenza virus infection: report of two cases].

We treated two children with influenza-associated acute encephalopathy by a combination of mild hypothermia and steroid pulse therapy. Case 1, a 2-year-and-3-month-old boy, admitted to our hospital 7 days after the onset of central nervous symptoms. The brain MRI-CT revealed laminar cortical necrosis and severe brain edema. EEG showed very low voltage. Brain edema improved by the combination therapy. He had sequelae, but was able to eat. Case 2, a 1-year-and-10-month-old boy, admitted to our hospital 5 days after the onset of central nervous symptoms. Brain MRI showed frontal dominant cortical edema. EEG showed high voltage delta bursts. The combination therapy was effective, but he remained mental handicapped. The outcome was better compared to our previous cases of acute encephalopathy. The combination therapy is intended to counteract cytokines, and was considered to be an effective treatment against acute encephalopathy associated with an influenza virus infection.

Child, Preschool↗