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S Leder

Publications and source records attributed to S Leder.

At least 19 recordsLinked to original sources
PubMed2000

Specificity determinants of substrate recognition by the protein kinase DYRK1A.

DYRK1A is a dual-specificity protein kinase that is thought to be involved in brain development. We identified a single phosphorylated amino acid residue in the DYRK substrate histone H3 (threonine 45) by mass spectrometry, phosphoamino acid analysis, and protein sequencing. Exchange of threonine 45 for alanine abolished phosphorylation of histone H3 by DYRK1A and by the related kinases DYRK1B, DYRK2, and DYRK3 but not by CLK3. In order to define the consensus sequence for the substrate specificity of DYRK1A, a library of 300 peptides was designed in variation of the H3 phosphorylation site. Evaluation of the phosphate incorporation into these peptides identified DYRK1A as a proline-directed kinase with a phosphorylation consensus sequence (RPX(S/T)P) similar to that of ERK2 (PX(S/T)P). A peptide designed after the optimal substrate sequence (DYRKtide) was efficiently phosphorylated by DYRK1A (K(m) = 35 microM) but not by ERK2. Both ERK2 and DYRK1A phosphorylated myelin basic protein, whereas only ERK2, but not DYRK1A, phosphorylated the mitogen-activated protein kinase substrate ELK-1. This marked difference in substrate specificity between DYRK1A and ERK2 can be explained by the requirement for an arginine at the P -3 site of DYRK substrates and its presumed interaction with aspartate 247 conserved in all DYRKs.

Amino Acid Sequence↗
PubMed1999

Cloning and characterization of DYRK1B, a novel member of the DYRK family of protein kinases.

The DYRK1A gene on human chromosome 21 encodes a protein kinase presumed to be involved in the pathogenesis of mental retardation in Down's syndrome. Here we describe a highly similar homolog, DYRK1B, which is, in contrast to DYRK1A, predominately expressed in muscle and testis. The human DYRK1B gene was mapped to chromosome 19 (19q12-13.11) by radiation hybrid analysis. The amino acid sequences of DYRK1A and DYRK1B are 84% identical in the N-terminus and the catalytic domain but show no extended sequence similarity in the C-terminal region. DYRK1B contains all motifs characteristic for the DYRK family of protein kinases. In addition, the sequence comprises a bipartite nuclear localization motif. A green fluorescent protein (GFP) fusion protein of DYRK1B was found mainly in the nucleus of transfected COS-7 cells. These data suggest that DYRK1B is a muscle- and testis-specific isoform of DYRK1A and is involved in the regulation of nuclear functions.

Amino Acid Sequence↗
PubMed1999

Alpha-galactosidase of Bifidobacterium adolescentis DSM 20083.

Bifidobacterium adolescentis was grown anaerobically in medium enriched with alpha-D-galactosides. alpha-Galactosidase (EC 3.2.1. 22) was released from the cells by ultrasonic treatment and purified 36-fold by ultrafiltration, ammonium-sulphate precipitation, anion-exchange chromatography, and size-exclusion chromatography. Two protein bands were consistantly observed after sodium-dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE). Electrophoretically homogeneous alpha-galactosidase was only obtained by electroelution. The enzyme had an apparent molecular mass of 344 kDa and 79 kDa as judged by size-exclusion chromatography and SDS-PAGE, respectively. Activity-staining after nondenaturing SDS-PAGE indicated an apparent molecular mass of 145 kDa. Thus, a tetrameric structure of the protein is suggested. The alpha-galactosidase showed optimal activity at pH 5.5 and 55 degrees C. Lower pH values and higher temperatures rapidly inactivated alpha-galactosidase. The enzyme hydrolyzed specifically alpha-galactosidic linkages, and alpha-(1-3)-linkages were hydrolyzed at a higher rate compared to alpha-(1-6)-linkages. Hydrolysis of galactosides followed normal saturation kinetics; KM-values for p-nitrophenyl-alpha-galactopyranoside (p-NPG) and raffinose were calculated with 0.957 mM and 4.12 mM, respectively.

Bifidobacterium↗
PubMed1995

[Bilateral occlusion of the internal carotid arteries. Analysis of a series of 19 patients].

The natural history of patients suffering from bilateral internal carotid occlusion is poorly known. We report a study of 19 patients presenting such a vascular condition as demonstrated by angiography. In all our cases, cardio-vascular risk factors were frequently found. Smoking was particularly frequent and present in 18 patients (95%). Presenting neurological episodes included either transient ischemic attack (8/19) or stroke (9/19). Associated arterial lesions were diffusely distributed on the other cerebral vessels, frequently involving the extra-cranial part of the vertebral arteries. Collateral circulation feeding the intracranial carotid system mainly, or exclusively, originated from the vertebro-basilar system. Ischemic strokes were frequently detected by cerebral CT scan. They were located in the middle cerebral territory or at the junctions between 2 major cerebral arteries. A radiological aspect of cortical atrophy was noted in 9 patients among 19. Regional cerebral blood flow assessed by Xe133 inhalation was usually normal at rest (16/19), but hyporeactivity to acetazolamide was found in 10 patients among 19. The latter was more frequent in patients suffering from arterial hypertension or diabetes mellitus. Our results confirm that the patients suffering atheromatous bilateral occlusion of the internal carotid arteries may survive with minimal neurological deficits. Collateral circulation is mainly provided by the vertebro-basilar system allowing to frequently maintain normal cerebral blood flow at rest.

Aged↗
PubMed1991

Cervical dystonia: clinical findings and associated movement disorders.

We studied 300 patients, 61% women, with mean age 49.7 years and mean duration of dystonia 7.8 years, to determine the demographic and clinical characteristics of cervical dystonia (CD) and its relationships to other movement disorders. Torticollis was present in 82%, laterocollis in 42%, retrocollis in 29%, and anterocollis in 25%; however, the majority (66%) had a combination of these abnormal postures. Scoliosis was present in 39%, local pain reported by 68%, and 32% had evidence of secondary cervical radiculopathy. In addition to CD, 16% of patients had oral dystonia, 12% mandibular dystonia, 10% hand/arm dystonia, and 10% had blepharospasm. Tremor was noted in 71% of patients; head-neck tremor was present in 60%, and tremor in other body regions was present in 32%. A family history of a movement disorder was present in 44% of the CD patients. Tardive dystonia was the cause in 6%; 11% had posttraumatic dystonia. Anticholinergic drugs provided moderate improvement in 33% of patients, but local intramuscular botulinum toxin injections relieved CD, local pain, or both in over 90% of all treated patients.

Adolescent↗
PubMed1989

Impact of dental conditions on patients' quality of life.

Quality of life measures have rarely been used in dentistry to assess oral health status. The purpose of this paper is to assess the utility of using standard indicators to measure the impacts of dental conditions on patients' quality of life. Quality of life was conceptualized as a multidimensional construct including three major aspects: social functioning, measured by the Sickness Impact Profile; well-being, measured by the Gill Well-Being Scale, Spielberger State/Trait Anxiety Scale, and the Corah Dental Anxiety Scale; and symptoms, measured by the Kiyak Oral Functioning Scale, the McGill Pain Questionnaire, and the West Haven Multidimensional Pain Inventory. 152 patients were recruited from private dental practices consisting of 48 TMJ, 33 periodontal, 23 denture, and 48 recall patients. Patients in the first three groups reported numerous impacts on quality of life and the impacts were particularly severe for the TMJ patients. The indicators used were sensitive to differences among the four groups and hold promise for further development of quality of life indicators for use in epidemiologic surveys and clinical dental trials.

Activities of Daily Living↗
PubMed1988

[The patient in psychotherapy].

Within the process of individual psychotherapy the author stresses the importance of understanding the initial everyday life view of "what is about being sick" for to establish a working, and cooperative setting. Thus, a three step procedure has been developed to guide the patient to a self responsible attitude toward conflicts and disease well at variance with common beliefs about healing, and the roles of the professional and his client herein.

Adaptation, Psychological↗
PubMed1978

[Sociodynamic aspects of psychotherapy].

Definitions of psychotherapy are determined by sociocultural and epistemological factors, which, in turn, influences the objectives and practical consequences of the use of psychotherapy (for example, selection, indication, and method used). The current state of knowledge and social needs tend to modify views of the role and functions of psychotherapy in medical and extramedical fields and areas, which sociodynamic aspects of psychotherapeutic processes and their applications being considered and utilized differently. It is within the framework of different social orders that potentially equivocal functions and ways of making use of psychotherapy can be either promoted or inhibited. Consequently, it is desirable to try to clarify corresponding prerequisites and conditions, which has been attempted by the author in his present paper.

Adaptation, Psychological↗
PubMed1968

[Early childhood brain damage and neuroses in adults].

Following some introductory remarks on the importance of multicausal factors in the genesis and development of neurotic disorders it is especially the part played by early-childhood cerebral lesions that is underscored by the author. The importance of this lesion to the development of neuroses in adults continues to be an open question. Within the framework of an attempt made with a view to finding an answer to this question the author presents the results of an analysis of 300 case histories of patients of the neurosis ward. After a description of an analysis of 22 patients diagnosed as having "neurosis", who had suffered from an early-childhood cerebral lesion, and of a comparison with a control group of anxiety-neurosis patients certain characteristics of these patients and of the clinical course of their disease are discussed. On the basis of this analysis there is then formulated a hypothetical model of the development of neurotic disturbances in the course of the lives of some persons with early-childhood cerebral lesions.

Adolescent↗