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Biomedical subjects

J E Olsson

Publications and source records attributed to J E Olsson.

At least 19 recordsLinked to original sources
PubMed1997

Ligand for EPH-related kinase (LERK) 7 is the preferred high affinity ligand for the HEK receptor.

HEK is a member of the EPH-like receptor tyrosine kinase family, which appear to have roles in development and oncogenesis. Recently, we purified a soluble HEK ligand which is also a ligand (AL1) for the HEK-related receptor EHK1. Promiscuity appears to be a characteristic feature of interactions between the EPH-like receptors and their ligands, termed ligands for EPH-related kinases (LERKs). This prompted us to analyze the interactions between the HEK exodomain and fusion proteins comprising candidate LERKs and the Fc portion of human IgG1 (Fc) or a FLAGTM-peptide tag by surface plasmon resonance, size exclusion high performance liquid chromatography, sedimentation equilibrium, and transphosphorylation. Our results indicate that AL1/LERK7 is the preferred high-affinity ligand for HEK, forming a stable 1:1 complex with a dissociation constant of 12 nM. As expected the apparent affinities of bivalent fusion proteins of LERKs and the Fc portion of human IgG1 had significantly reduced dissociation rates compared with their monovalent, FLAGTM-tagged derivatives. High-avidity binding of monovalent ligands can be achieved by antibody-mediated cross-linking of monovalent ligands and with LERK7 results in specific phosphorylation of the receptor. By extrapolation, our findings indicate that some of the reported LERK-receptor interactions are a consequence of the use of bivalent ligand or receptor constructs and may be functionally irrelevant.

Cells, Cultured↗
PubMed1997

Tolcapone added to levodopa in stable parkinsonian patients: a double-blind placebo-controlled study. Tolcapone in Parkinson's Disease Study Group II (TIPS II).

The primary objective of this study was to assess the effect of tolcapone on levodopa dosage in parkinsonian patients whose "wearing-off" phenomenon has been controlled with more frequent levodopa dosage. After a 1-week placebo run-in, 97 patients were assigned randomly to receive placebo or tolcapone 200 or 400 mg three times daily (t.i.d.). Levodopa dosage was reduced by -35% on day 1 of study and subsequently retitrated as required. After 6 weeks, the tolcapone groups crossed over to receive the other dose for a further 3 weeks for exploratory purposes. Both tolcapone groups had greater reductions in levodopa dosage than the placebo group at week 6 (not statistically different). The 200-mg t.i.d. group showed greatest improvement in estimated mean scores for all efficacy parameters (p < 0.05 versus placebo for change in Unified Parkinson's Disease Rating Scale Subscale II). Fewer dopaminergic and nondopaminergic adverse events were associated with tolcapone 200 mg t.i.d. than with tolcapone 400 mg t.i.d. The most frequently reported dopaminergic adverse events were nausea, cramps, dyskinesia, and dystonia. The most frequently reported unanticipated adverse event was diarrhea. Tolcapone 200 mg t.i.d. may provide additional benefit to patients with moderately advanced Parkinson's disease with treated "wearing-off" phenomenon.

Activities of Daily Living↗
PubMed1997

Human beta-trace in normal and pathological CNS tissues, genital organs and body fluids.

The function of BTP is still unknown. In CNS, the high amount of BTP in the white CNS matter and the glial cells as well as in genital organs of the stroma of epididymis suggest that BTP has a supportive function. Slight evidence of a synthesis in patients with MS and slightly increased CSF values in stroke patients may suggest that BTP is involved in repair mechanism of damaged brain tissue, or may be related from destroyed brain tissue. In samples of CSF, determination of BTP could be of value as differentiating glial cell tumors from tumors of other kinds, as well as the recently suggested diagnostic value of the Creutzfeldt-Jakob disease (20). However, also other functions of BTP has been suggested. (21, 22).

Animals↗
PubMed1997

The evaluation of facial paralysis.

The clinician faces a major challenge in the evaluation of acute facial nerve paralysis. Not only must he or she differentiate the large proportion of patients with idiopathic palsy who will resolve spontaneously from that critical small group that will not, but must also diagnose correctly the other rather unusual to rare conditions that cause facial paralysis. This article reviews the differential diagnosis, initial clinical evaluation, natural history, and long-term follow up of patients with acute facial dysfunction.

Audiometry↗
PubMed1996

Transgenic mice carrying the dominant rhodopsin mutation P347S: evidence for defective vectorial transport of rhodopsin to the outer segments.

To explore the pathogenic mechanism of dominant mutations affecting the carboxyl terminus of rhodopsin that cause retinitis pigmentosa, we generated five lines of transgenic mice carrying the proline-347 to serine (P347S) mutation. The severity of photoreceptor degeneration correlated with the levels of transgene expression in these lines. Visual function as measured by the electroretinogram was approximately normal at an early age when there was little histologic evidence of photoreceptor degeneration, but it deteriorated as photoreceptors degenerated. Immunocytochemical staining showed the mutant rhodopsin predominantly in the outer segments prior to histologically evident degeneration, a finding supported by quantitation of signal intensities in different regions of the photoreceptor cells by confocal microscopy. A distinct histopathologic abnormality was the accumulation of submicrometer-sized vesicles extracellularly near the junction between inner and outer segments. The extracellular vesicles were bound by a single membrane that apparently contained rhodopsin as revealed by ultrastructural immunocytochemical staining with anti-rhodopsin antibodies. The outer segments, although shortened, contained well-packed discs. Proliferation of the endoplasmic reticulum as reported in Drosophila expressing dominant rhodopsin mutations was not observed. The accumulation of rhodopsinladen vesicles likely represents aberrant transport of rhodopsin from the inner segments to the nascent disc membranes of the outer segments. It is possible that photoreceptor degeneration occurs because of a failure to renew outer segments at a normal rate, thereby leading to a progressive shortening of outer segments, or because of the loss of cellular contents to the extracellular space, or because of both.

Animals↗
PubMed1996

Embryonic stem cells express multiple Eph-subfamily receptor tyrosine kinases.

Eph and its homologues form the largest subfamily of receptor tyrosine kinases. Normal expression patterns of this subfamily indicate roles in differentiation and development, whereas their overexpression has been linked to oncogenesis. This study investigated the potential role of Eph-related molecules during very early embryonic development by examining their expression in embryonic stem (ES) cells and embryoid bodies differentiated from ES cells in vitro. By use of a strategy based on reverse transcriptase-mediated PCR, nine clones containing Eph-subfamily sequence were isolated from ES cells. Of these, eight were almost identical to one of four previously identified molecules (Sek, Nuk, Eck, and Mek4). However, one clone contained sequence from a novel Eph-subfamily member, which was termed embryonic stem-cell kinase or Esk. Northern analysis showed expression of Esk in ES cells, embryoid bodies, day 12 mouse embryos, and some tissues of the adult animal. Levels of expression were similar in ES cells and embryoid bodies. By comparison, Mek4 showed no significant transcription in the ES cell cultures by Northern analysis, whereas Eck displayed stronger signals in ES cells than in the embryoid bodies. These results suggest that Eph-subfamily molecules may play roles during the earliest phases of embryogenesis. Furthermore, the relative importance of different members of this subfamily appears to change as development proceeds.

Amino Acid Sequence↗
PubMed1996

Age-standardized incidence and prevalence of Parkinson's disease in a Swedish community.

Parkinson's disease (PD) shows a geographical variation. All prescriptions for anti-parkinsonian drugs were recorded for a half-year in a region with low L-dopa consumption. Hospital and outpatient records were studied and physicians were asked to supply details of PD patients in the region, with 147,777 inhabitants. The crude prevalence was 115 PD per 100,000 inhabitants, based on 170 cases. In contrast to other studies we report an age-standardized prevalence, which was 76 per 100,000, using the European Standard Population as reference. The corresponding approximate incidences were 11.0 (crude) and 7.9 (age-standardized) per 100,000 person-years. Male preponderance appeared in all age groups. Mean age at onset was 65.6 years, the highest figure reported. Variation between studies for age at onset, differences in prevalence, and male preponderance suggest environmental risk factors to be of importance for PD.

Adult↗
PubMed1995

Assessment of rehabilitation technologies in stroke. Outcomes and costs.

Initial functional ability (Barthel Index, mean 57) was found to be an important predictor of functional ability 1 year after stroke (mean 80) and for costs during the period. On average the total cost for a stroke patient was about SEK 200,000; the main expense, accommodation, averaged about SEK 140,000, while assistive devices amounted to SEK 2,600. Those who use assistive devices, although having achieved a high functional ability, perceive and rate their life situation (Nottingham Health Profile) considerably more impaired than those without assistive devices.

Aged↗
PubMed1994

[Binswanger disease. A blood pressure-related dementia].

Interest in Binswanger's disease has increased during the past decade, owing to the possibility of detecting white matter changes with computerised and magnetic resonance tomography. This paper consists in a summary of clinical symptoms and signs and possible diagnostic criteria, discussion of differential diagnosis, and the presentation of two own cases. Both patients manifested mild dementia and gait disturbance, and one had frequent drop attacks. Severe supra- and infra-tentorial white matter changes were present in both cases. It is important to consider a possible diagnosis of Binswanger's disease, as treatment of the appropriate risk factors may prevent or delay the development of dementia.

Aged↗
PubMed1994

Work-related, noise-induced hearing loss: evaluation including evoked potential audiometry.

This article reviews the evaluation of 246 workers (492 ears) who underwent otologic and audiologic testing as part of a worker's compensation claim for work-related, noise-induced hearing loss. Tinnitus was present in 58% of the patients, but was rarely a major symptom. Other otologic symptoms or a history of ear disease were virtually nonexistent. Standard audiometry showed a downsloping, high-frequency sensorineural hearing loss in 85% of the ears tested, with only 37% having a characteristic "noise notch" at 4000 or 6000 hertz. Asymmetric hearing loss was not uncommon, with 48 patients (20%) undergoing magnetic resonance scanning, all of whom showed no central lesion responsible for the loss. Proven malingering was surprisingly uncommon (9%). In this study, evoked response audiometry was a valuable adjunct to confirm behavioral thresholds in the evaluation of possible work-related, noise-induced hearing loss. The middle latency response was more effective than the auditory brainstem response as a result of the high-frequency steepness of the audiometric curve.

Acoustic Stimulation↗
PubMed1992

Dopa-responsive dystonia with depigmentation of the substantia nigra and formation of Lewy bodies.

The patient, who died at 23 years of age, was first diagnosed when she was 12 year old as having a dopa-responsive dystonia with decreased concentrations of monoamine metabolites in the cerebrospinal fluid. Also the concentrations of other neurotransmitters including somatostatin, substance P and metenkefalin were lowered indicating a more widespread damage of the cerebral neurotransmitter systems. At autopsy the brain was essentially intact except for pronounced gliosis and extreme loss of melanotic nerve cells in the substantia nigra. Several remaining nerve cells showed the presence of Lewy bodies.

Adult↗
PubMed1992

Transgenic mice with a rhodopsin mutation (Pro23His): a mouse model of autosomal dominant retinitis pigmentosa.

We inserted into the germline of mice either a mutant or wild-type allele from a patient with retinitis pigmentosa and a missense mutation (P23H) in the rhodopsin gene. All three lines of transgenic mice with the mutant allele developed photoreceptor degeneration; the one with the least severe retinal photoreceptor degeneration had the lowest transgene expression, which was one-sixth the level of endogenous murine rod opsin. Of two lines of mice with the wild-type allele, one expressed approximately equal amounts of transgenic and murine opsin and maintained normal retinal function and structure. The other expressed approximately 5 times more transgenic than murine opsin and developed a retinal degeneration similar to that found in mice carrying a mutant allele, presumably due to the overexpression of this protein. Our findings help to establish the pathogenicity of mutant human P23H rod opsin and suggest that overexpression of wild-type human rod opsin leads to a remarkably similar photoreceptor degeneration.

Animals↗