Four P-like elements are required for optimal transcription of the mouse IL-4 gene: involvement of a distinct set of nuclear factor of activated T cells and activator protein-1 family proteins.

We previously identified the P sequence as a critical regulatory element of the human IL-4 promoter. In the mouse IL-4 promoter, there are five elements homologous to the human P sequence designated conserved lymphokine element 0 (CLE0), P, P2, P3 and P4. To characterize the role of these P-like elements and their binding factors in the native promoter, we did transient transfection and electrophoretic mobility shift assays (EMSA).

Low epithelial cell proliferation and absence of oncoprotein expression in juvenile polyposis of the stomach, with or without tumors.

Objectives: To assess cell proliferation and analyze oncogenetic abnormalities in cases of juvenile polyposis of the stomach (JPs), with or without coexisting tumors.

Methods: The Ki-67 labeling indices (KLI) were compared for juvenile polyps and coexisting tumors in three cases of JPs along with values for gastritis, foveolar epithelial hyperplastic polyps, adenomas, and carcinomas. Expression of p53, Bcl-2, and c-ErbB-2 in tumors was examined immunohistochemically, and a search for c-Ki-ras mutations was made by DNA direct sequencing.

Apolipoprotein E in progressive supranuclear palsy in Japan.

Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease which shows several psychiatric and neurologic symptoms: pseudobulbar palsy, supranuclear ocular palsy, extrapyramidal rigidity, gait ataxia, and dementia. Almost all cases seem to be sporadic; therefore, the elucidation of risk factors is important to clarify the pathological mechanism. Apolipoprotein E4 (ApoE4) is now well established as a risk factor of Alzheimer's disease (AD).

Neuropathology of the dentate nucleus in developmental disorders.

The dentate nucleus was examined histologically and immunohistochemically in 47 cases of nonprogressive developmental disorders. Neuronal loss and/or atrophy was observed in 13 cases, while mild neuronal lesions, characterized by dendritic swelling and/or the appearance of eosinophilic materials around the neurons, were exhibited in 20 cases. The former change was accompanied by diffuse central nervous system involvement, and the etiology was perinatal hypoxic ischemic encephalopathy, acute encephalopathy, and meningoencephalitis in most cases.

Neuronal inclusions in the dentate fascia in patients with multiple system atrophy.

Ubiquitin-immunoreactive neuronal inclusions in the granular cells in the dentate fascia (UNIDs) of patients with multiple system atrophy (MSA) were examined for immunohistochemical and ultrastructural characterization especially in comparison with those which were recently reported for amyotrophic lateral sclerosis with dementia (ALS-D). Eight of 23 MSA patients had UNIDs which were also identified by Gallyas-Braak impregnation but immunonegative for other antibodies including against tau, neurofilaments, and alphaB crystallin. Ultrastructurally, loosely aggregated fibrils without limiting membrane located around the nucleus, which was confirmed by the results of ubiquitin-immunoelectron microscopy.

Focal cortical dysplasia: appearance on MR images.

Purpose: To clarify the magnetic resonance (MR) imaging characteristics of focal cortical dysplasia (FCD).

Materials And Methods: The authors reviewed the MR images of 14 patients with FCD, which was confirmed with histologic examination.

Results: MR images exhibited FCD in 13 of the 14 patients.

[Proton MR spectroscopy of hyperplastic hematopoietic marrow in aplastic anemia].

The purpose of this study was to compare the findings of magnetic resonance (MR) spectroscopy of hyperplastic hematopoietic marrow with those of normal bone marrow. Twenty-four samples of normal marrow from eight control subjects and 19 samples of hyperplastic marrow in aplastic anemia were examined with a 1.5T MR unit.

Control of NFATx1 nuclear translocation by a calcineurin-regulated inhibitory domain.

The nuclear factor of activated T cells (NFAT) regulates cytokine gene expression in T cells through cis-acting elements located in the promoters of several cytokine genes. NFATx1, which is preferentially expressed in the thymus and peripheral blood leukocytes, is one of four members of the NFAT family of transcription factors. We have performed domain analysis of NFATx1 by examining the effects of deletion mutations.

[Pathological spectrum of neuronal migration disorder].

A variety of brain malformative lesions, resulting mainly from abnormalities in neuronal migration, have been recently highlighted with increasing knowledge on surgical pathology of intractable epilepsy. In this article, a wide spectrum of pathology in and around the neuronal migration period are reviewed. Morphological changes of lissencephalies, polymicrogyria, microdysgenesis and focal cortical dysplasia were described, as well as some problems in the classification of malformative brains.

Cytokine signal networks and a new era in biomedical research.

Elucidation of the biochemical nature of the signal transduction pathway that regulate transcription and replication is the focus of attention in molecular biology. This research may make feasible manipulation of growth and differentiation of mammalian cells, which in turn would have profound implication in biomedical research on cell and gene therapy, and development of pharmaceutical products. Cytokines control growth, differentiation, death, and function of cells of lymphocytic, hemopoietic systems, and together with nerve cells provide a pertinent model to study intercellular communications and intercellular signal networks.

Calcineurin-dependent nuclear translocation of a murine transcription factor NFATx: molecular cloning and functional characterization.

Members of the nuclear factor of activated T cells (NFAT) are involved in the induction of a number of cytokine genes. We report here cDNA cloning and chromosomal localization of a murine homologue of human NFATx, designated as mNFATx1, and its splicing variants mNFATx2 and m delta NFATx. Northern blot analysis showed mNFATx1 to be predominantly expressed in the thymus.

Progressive supranuclear palsy with asymmetric lesions in the thalamus and cerebellum, with special reference to the unilateral predominance of many torpedoes.

This report concerns a notable case of progressive supranuclear palsy exhibiting asymmetric dentate nucleus and thalamic degeneration with numerous torpedoes. The neuronal loss in the ventral lateral nucleus of the thalamus was predominant on the right side, while in the cerebellum, a quantitative study revealed the contralateral predominance of the neuronal loss in the dentate nuclei and torpedo formation, with preserved Purkinje cells. The abnormal tau-protein-related profiles in the two nuclei did not show any laterality in their distribution, indicating that the dentatothalamic tract may have been affected in a non-specific way in this case.

Effect of cabergoline, a long-acting dopamine D2 agonist, on reserpine-treated rodents.

We studied the characterization of cabergoline, a new ergot alkaloid derivative and a selective dopamine D2 receptor agonist, in comparison to bromocriptine and pergolide in reserpine-treated rodents. Cabergoline (0.25-1.

Absence of SOD1 gene abnormalities in familial amyotrophic lateral sclerosis with posterior column involvement without Lewy-body-like hyaline inclusions.

A 65-year-old man with familial amyotrophic lateral sclerosis (ALS) with posterior column involvement showed fairly slow progression of the illness and lived with the aid of a respirator for 12 years. Neuropathological examinations showed simultaneous involvement of the pyramidal tract and lower motor neurons as well as degeneration in the Clarke's nucleus- spinocerebellar tract-middle root zone of the posterior column, the pallidoluysian system, the medullary reticular formation, and widespread anterolateral columns of the spinal cord. However, the patient had no Lewy-body-like hyaline inclusions, which are characteristic features of this form of familial ALS.

Dopamine receptor affinities in vitro and stereotypic activities in vivo of cabergoline in rats.

An ergot alkaloid derivative, cabergoline, and its metabolites were investigated for their affinities for dopamine D1 and D2 receptors in rat striatum in vitro in comparison with those of bromocriptine and pergolide. The affinity for D1 receptors was in the following order: pergolide > des-dimethylaminopropyl cabergoline (FCE21904) > cabergoline > or = bromocriptine > or = des-methyl cabergoline (FCE27395) > or = des-ethylcarbamoyl cabergoline (FCE21590). From the effects of GTP on these affinities for the D1 receptor, cabergoline, some of its metabolites, and pergolide were characterized as agonists in contrast to bromocriptine which was classified as an antagonist.

Signal transduction in Th clones: target of differential modulation by PGE2 may reside downstream of the PKC-dependent pathway.

Lymphokines produced by non-transformed Th clones, Th1 and Th2, were classified into three groups based on their patterns of expression by different stimuli: Group I, GM-CSF and IL-2, characterized by a strict requirement of activation of both the PKC- and calcium-dependent pathways; Group II, IFN-gamma, IL-3, and IL-4, partially induced by calcium ionophore alone; and Group III, IL-5, IL-6, and IL-10, partially induced by either PMA or calcium ionophore alone. Transfection of constitutively active PKC or p21ras replaced the requirement for PMA in expression of these lymphokines, with the exception of GM-CSF. Production of Group II lymphokines was partially induced by constitutively active calcineurin.

Surgical treatment of children with medically intractable epilepsy--outcome of various surgical procedures.

Outcome after temporal lobe resection, extratemporal resection, and corpus callosotomy was studied in 33 children aged 15 years or less with medically intractable epilepsy. Seizure-free control was achieved in 67% (6/9) of pediatric patients versus 67% (60/90) of adult patients receiving temporal lobe resection and in 33% (4/12) of pediatric patients versus 25% (7/28) of adult patients receiving extratemporal resection. Among patients suffering from drop attacks and generalized convulsive seizures, 42% (5/12) of pediatric patients versus 25% (6/24) of adult patients receiving corpus callosotomy became seizure-free.

Noninvasive evaluation of malignancy of brain tumors with proton MR spectroscopy.

Purpose: To test clinical proton MR spectroscopy as a noninvasive method for predicting tumor malignancy.

Methods: Water-suppressed single-voxel point resolved spectroscopy in the frontal white matter of 17 healthy volunteers and 25 patients with brain tumors yielded spectra with peaks of N-acetyl aspartate (NAA), choline-containing compounds (Cho), creatine/phosphocreatine (Cre), and lactate. These peak intensities were semiquantitated as a ratio to that of the external reference.

[The dose-response relationship in treatment of strabismus with botulinum toxin].

The dose-response relationship between botulinum toxin and the alteration of ocular alignment of 15 esotropia cases (ET) and 15 exotropia cases (XT) was evaluated. We began with a dose of 0.25 units (U) per injection and stepped it up to 2.

Combined effects of cabergoline and L-dopa on parkinsonism in MPTP-treated cynomolgus monkeys.

The behavioral effects of L-dopa or cabergoline alone were compared with those of the joint administration of the two drugs in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned parkinsonian cynomolgus monkeys with attention to the induction of hyperactivity and dyskinesia. Cabergoline alone at 0.2 mg/kg or less improved in a dose-dependent fashion the parkinsonism without inducing hyperactivity and dyskinesia following a single subcutaneous injection.