Disturbance of verticality perception and postural dysfunction in Parkinson's disease.

OBJECTIVES: Verticality perception is known to be abnormal in Parkinson's disease (PD), but in which stage respective dysfunctions arise and how they relate to postural disorders remains to be settled. These issues were studied with respect to different dimensions of the subjective visual vertical (SVV) in relation to clinical parameters of postural control. MATERIALS & METHODS: All participants had to orientate a luminous line at random planar orientations to a strictly vertical position using an automated operator system. The SVV was analyzed in 58 PD patients and 28 control subjects with respect to (i) the angle between true and subjective vertical (deviation) and (ii) the variability of this across five measurements (variability). Results were referred to the subjective upright head position (SUH), the disease stage, and clinical gait/balance features assessed by the MDS-UPDRS and the Tinetti test. RESULTS: Parkinson's disease patients had significantly higher SVV deviation and variability than controls. With respect to disease stage, deviation developed before abnormal variability. SVV variability was associated with poor balance and gait performance, as well as postural instability. Deficits in SUH and SVV deviation were correlated and mostly unidirectional, but did not correspond to the side of motor symptom dominance. CONCLUSIONS: Visual verticality perception in PD is deviated already in early stages, conceivably as a relatively static internal misrepresentation of object orientation. Variability about verticality perception emerges in more advanced stages and is associated with postural and balance abnormalities.

Multiple forms of glycoproteins in the secretory product of the bovine subcommissural organ--an ancient glial structure.

The glial subcommissural organ (SCO) is a conserved structure of the vertebrate brain that secretes a glycoprotein-rich product into both the extracellular matrix and the cerebrospinal fluid of the third ventricle that forms Reissner's fibre (RF). In order to identify specific secretory proteins of the subcommissural organ, a panel of antigen- and epitope-specific monoclonal antibodies was raised against bovine RF to study the distribution of epitopes in Western blots of bovine RF. Six groups of epitopes that were specific for SCO secretion were distinguished on the basis of their phylogenetic conservation and their different grades of resistance against chemical denaturation. The monoclonal antibody aRFME 4 recognised a carbohydrate-containing epitope that was strongly conserved in vertebrates and unique for SCO secretion. All epitopes showed essentially the same distribution pattern over 15 bovine RF glycoprotein fractions of different molecular masses in immunoblots indicating that the different RF fractions are closely related. They may represent multiple forms of SCO spondin.

A possible role of N-cadherin in thalidomide teratogenicity.

Several experimental findings indicate that the adhesion molecule N-cadherin participates in distinct processes of embryogenesis that spatiotemporarily correlate with high sensitivity to thalidomide. Therefore, we suppose that thalidomide might interfere with N-cadherin-mediated interactions. This hypothesis is supported by protein-ligand docking studies simulating and characterizing the binding of thalidomide to N-cadherin molecules. Thalidomide was found to bind at the N-terminal domain of N-cadherin mimicking a tryptophan residue which is critical for the homodimerization of the adhesion molecule. Based on these results, we suggest that thalidomide might disturb cellular recognition and migration processes in morphogenesis by interaction with N-cadherin.

Reissner's substance expressed as a transient pattern in vertebrate floor plate.

The function of the floor plate in dorso-ventral patterning of the developing nervous system and in the guidance of commissural axons is well established. However, several morphological aspects concerning the exact localization of its rostral and caudal end and the regional and temporal specialization are still controversial. We present new insights revealed by the expression of Reissner's substance in the floor plate during early neurogenesis of zebrafish, Xenopus, chick and rat. We used a polyclonal antiserum raised against Reissner's substance, which is a secretory product of radial glia in the roof plate of the adult vertebrate brain. In early embryonic stages the rostral boundary of floor plate immunoreaction vary in the different vertebrates. Immunoreactive cells are not only present in the epichordal region (rat) but also in prechordal areas of the midbrain (chick) and forebrain (zebrafish and Xenopus). During further development, Reissner's substance expression disappears first in the most rostral areas and later also in the spinal cord. However, immunopositive labelling in the isthmus region at the mes-metencephalic boundary, described originally as the flexural organ, is most extensive and detectable during a long period of embryonic development. It is proposed that the gradual restriction of Reissner's substance expression to the isthmus reflects the complex differentiation processes in this region also in later embryonic development. Furthermore, the expression pattern in zebrafish indicates that Reissner's substance could play a role in axonal decussation.

Radial secretory glia conserved in the postnatal vertebrate brain: a study in the rat.

Secretory glial cells in the roof of the last diencephalic prosomer, ependymocytes and hypendymocytes, form the subcommissural organ. The cells of this complex were labelled immunocytochemically, using an antiserum against their specific secretory products. The study aims at the characterization of this cell type in the rat as an anatomical model situation. Radially oriented secretory glial cells remain after birth behind the posterior commissure in the mesencephalic aqueduct. At about postnatal day 10, the cell bodies descend into the conventional ependyma and at postnatal day 25 they assume a compact, rounded appearance. The secretory product they release is involved in the formation of Reissner's fiber. This differentiation in phenotype is not accompanied by a change of the intermediate filament expression. In the adult rat these cells had been labelled immunopositive for cytokeratins 8 and 18 as well as vimentin but not for glial fibrillary acidic protein. DiI-marking from the third ventricle and from the dorsal surface of the brain shows that the basal processes of ependymocytes and hypendymocytes project to the external and internal glial limiting membrane, respectively, through the commissural fiber bundles. Also the subependymal located hypendymocytes have apical processes with contacts to the cerebrospinal fluid. When this secretory cell population is studied with respect to cyto-architectonical changes during ontogeny the results lead to a new understanding of the subcommissural cells. They are not specialized ependymal cells in a regionally restricted and secondary differentiated ependymal area, but rather descendants of an ontogenetically ancient, specific type of radial glia. Characteristic features for all subcommissural cells are that they: (1) appear very early during ontogeny, (2) are derived from a radial oriented glial cell type, (3) carry at least one kinocilium, (4) possess an original intermediate filament pattern, (5) release a secretory product.

Assessing the efficacy of an academic hearing peer tutor for a profoundly deaf student.

This study assessed the efficacy of using a hearing peer tutor to provide math instruction for a profoundly deaf sixth-grade girl. Instruction was provided for twenty minutes each day. A changing criterion design was employed to measure the tutee's progress across four math objectives she had not previously mastered. The peer tutoring intervention was highly successful, with the tutee meeting the criterion of 70 percent accuracy for three consecutive days for each of the four curriculum objectives after only a brief period of intervention. Peer tutoring is discussed as a potentially useful vehicle for mainstreaming deaf children.

Tissue culture of bovine subcommissural organ.

Tissue of the secretory, glial subcommissural organ (SCO) of adult, male cattle was cultured in serum-free medium for 70 days in vitro. Only minor alterations in the histoarchitecture and the cytology of the explanted SCOs could be observed by light and electron microscopy. Light- and electron-microscopic immunocytochemical investigations with an antiserum raised against bovine SCO secretory proteins revealed intra- and extra-cellularly localized immunoreactive material in tissue sections of SCO explants cultured up to 69 days in vitro. An indirect competition enzyme-linked immunosorbent assay (ELISA) was developed to detect minor quantities of SCO secretory products. By means of this assay, approximately 35 ng RF protein per ml was detected in culture medium supernatants conditioned for 3 days in SCO tissue cultures at 3, 38, and 69 days in vitro. These studies demonstrate that the bovine SCO can maintain its secretory activity throughout long periods in vitro.

Immunological cross-reactivities between proteins secreted by the subcommissural organ, and plant lectins.

The glial subcommissural organ (SCO) discharges a glycoprotein-rich secretory product into the third ventricle to form Reissner's fibre (RF). The SCO proteins bear N-linked oligosaccharides, such as mediate many cell-cell and cell-matrix interactions. In such interactions the corresponding partner molecule recognising the sugar chain is often a sugar-specific protein (lectin). We present here evidence that the constituents of the SCO secretory product include proteins immunologically cross-reactive with certain plant lectins. Polyclonal antisera directed against Phaseolus vulgaris agglutinin-L (PHA-L) labelled the apically released RF-material of the rat SCO. Indirect ELISA studies shows in addition that anti-RF antisera bound to certain plant lectins (PHA-L, Con A). Dot spot assays demonstrated binding of anti-PHA-L to RF proteins. In Western blots of RF proteins anti-PHA-L, anti-RCA and anti-Con A bound to distinctive subsets of the RF protein fractions.

[Dosage reduction of d-phe-6-GnRH for the regulation of ovulation by complexation with polyglycine]. / Dosisminderung von D-Phe6-GnRH bei der Ovulationsregulierung durch Komplexierung mit Polyglycin.

The gonadotropin-releasing-hormone analogue D-Phe6-GnRH was complexed with polyglycine under non-denaturing conditions. The liberation behaviour of these complexes was investigated in vitro in dependence of hormone content. The "effective dose 50" (ED 50) could be decreased by factor 34 in vivo in mouse ovulation test by reason of protection effect of polyglycine for the hormone against untimely proteolytical degradation.

[Occupational disability among teachers and its relation to subjective health status and professional performance]. / Arbeitsunfähigkeit bei Pädagogen und deren Beziehungen zum subjektiven Gesundheitszustand und der beruflichen Leistungsfähigkeit.

The aim of this study was to examine the relationship between absenteeism and functional health state, action competence, realization of professional goals and essential needs as well as subjective strain in job and family and type A behaviour pattern. The results of discriminant analyses from a sample of 774 teachers (group 1; no sickness leave days, group 2: sickness leave days greater than 28) are discussed.

[Insulin polyamino acid complexes--a variable principle in the preparation of sustained-release forms]. / Insulin-Polyaminosäure-Komplexe--ein variationsfähiges Prinzip zur Gewinnung von Verzögerungsformen.

Polyglycine, polyalanine, polyleucine, poly-alpha-glutamic acid, poly-gamma-glutamic acid and poly-alpha-lysine were complexed with insulin under non denaturating conditions. The liberation behaviour of the hormone was investigated in vivo and in vitro in dependence of the insulin content, mole mass, ionic interaction and hydrophobicity of the polyamino acid. The in vitro results were mainly confirmed by animal experiments and indicated distinct effects of the physiochemical parameters to the bioavailability of insulin. The complex of poly-alpha-lysine and polyglycine were shown to be the most suited retard form, producing significant blood glucose lowering effects up to 12 hours.

[A simple method of preparation of keratin filaments and production of a polyclonal broad-spectrum anti-cytokeratin antiserum for immunohistochemical application in fixed and unfixed epithelial tissues]. / Ein einfaches Verfahren der Präparation von Keratinfilamenten und Herstellung eines polyklonalen Breitspektrum-Anti-Zytokeratin-Antiserums für die immunhistochemische Anwendung bei fixierten und unfixierten epithelialen Geweben.

Rabbits were immunized with 10 nm filaments of a mixture of cytokeratins which has been isolated from human heel callus material and reconstituted to filaments in vitro. The antisera to keratins (ASK) have been tested histologically at fixed and unfixed tissue samples by means of the indirect immunofluorescence and PAP technique. The ASK recognized specifically only the epithelial cells of skin, of the mucous membranes of mouth and digestive tract, of salivary glands, sweat gland and mammary gland, but did not react with hepatocytes or kidney cells. The following tumors, tested till now, reacted with the antikeratin antisera: epithelial and lymphoepithelial carcinomas of skin, mouth and digestive tract, carcinomas of salivary glands, mammary gland and thyroid gland, adamantinoma, basalioma of skin, and metastases from carcinomas.

Immuno-electron-microscopic analysis of the basal route of secretion in the subcommissural organ of the rabbit.

Low-temperature-embedded tissue of the subcommissural organ (SCO) of the rabbit was analyzed for the basal route of secretory product by means of indirect immuno-metal cytochemistry (protein A-gold technique) at the electron-microscopic level. By use of (1) an antiserum against bovine Reissner's fibre (see Sterba et al. 1981) and, thereafter, (2) particulate gold-marker solution, immunoreactive sites could be clearly visualized within the extracellular matrix of both (a) the basal part of the ependymal cell layer, and (b) the hypendyma proper. Abundant secretory material was identified within (i) dilated intercellular spaces (a + b) as well as (ii) branching basal lamina labyrinths and distinct perivascular spaces (b). All these compartments are thought to belong to a system of extracellular channels, which may function in secretion directed toward hypendymal blood vessels.

[Immunohistochemical investigations on the ontogenesis of the subcommissural organ]. / Immunhistochemische Untersuchungen zur Ontogenese des Subcommissuralorgans.

Using an antiserum raised against bovine Reissner's fiber a ventricle border of the matrix epithel reacting in the immunohistochemical procedure according to Sternberger et al. (1970) is visible in the very early stage of the embryonic brain of Pleurodeles waltli. In the basal region of the brain the immunoreactive border later develops into the flexural organ a secretory cell formation that is situated in the deuterencephalon and spinal cord. The cells of the flexural organ release a glycoprotein into the cerebrospinal fluid, where, among other things, the Reissner's fiber is formed. Later on, Reissner's fiber is produced no longer by the flexural organ, but the subcommissural organ. It is suggested that in the very early embryonic stage the immunohistochemically reactive ventricle border, too, contains a glycoprotein that might contribute to any events in the ontogeny of the nervous system.

Preparation and discharge of secretion in the subcommissural organ of the rat. An electron-microscopic immunocytochemical study.

The secretion of the subcommissural organ (SCO) of the rat was studied by means of immunocytochemistry at the electron-microscopic level with the use of (1) the polar embedding medium Lowicryl K4M at -30 degrees C, (2) the protein A-gold technique, and (3) a rabbit antiserum against bovine Reissner's fiber (see Sterba et al. 1981). Two different substructures of the ependymal and the hypendymal SCO-cells display a positive immunocytochemical reaction: (1) sacs containing flocculent secretion, which originate from the granular endoplasmic reticulum, and (2) vacuoles filled with fine granular secretion, which are pinched off from the Golgi apparatus. The secretory material of the sacs and the vacuoles is discharged both (i) apically into the cerebrospinal fluid and (ii) basally into intercellular spaces of the SCO-hypendyma. The apically released secretion is condensed to a lamina-like formation, which more caudally assumes the form of Reissner's fiber. The route of the basally released secretion remains, however, vague. The "periodically striated bodies", which were thought to be morphological mediators of the discharge of the secretion into the capillaries, are never labeled by gold particles.

[Immunocytochemical demonstration of neuropeptides (neurophysin and oxytocin) by the protein A-gold technic]. / Immuncytochemische Darstellung von Neuropeptiden (Neurophysin und Oxytocin) mit der Protein-A-Gold-Technik.

In the classic peptidergic neurosecretory system of vertebrates the neurohormone oxytocin is associated with the carrier protein neurophysin. By using small gold particles (3 to 12 nm) in the protein A-gold technique, both the hormone and the carrier-protein will be labelled, while larger particles (20 nm) label only the neurophysin. To bind the latter particles, a greater number of Fc-regions of antigen-IgG-complexes seems to be necessary.