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Biomedical subjects

A Becker

Publications and source records attributed to A Becker.

At least 37 records · Page 2Linked to original sources

Expression of a functional chimeric Ig-MHC class II protein.

We have generated a chimeric protein molecule composed of the alpha- and beta-chains of the MHC class II I-E molecule fused to antibody V regions derived from anti-human CD4 mAb MT310. Expression vectors were constructed containing the functional, rearranged gene segments coding for the V region domains of the antibody H and L chains in place of the first domains of the complete structural genes of the I-E alpha- and beta-chains, respectively. Cells transfected with both hybrid genes expressed a stable protein product on the cell surface. The chimeric molecule exhibited the idiotype of the antibody MT310 as shown by binding to the anti-idiotypic mAb 20-46. A protein of the anticipated molecular mass was immunoprecipitated with anti-mouse IgG antiserum. Furthermore, human soluble CD4 did bind to the transfected cell line, demonstrating that the chimeric protein possessed the binding capacity of the original mAb. Thus, the hybrid molecule retained: 1) the properties of a MHC class II protein with regard to correct chain assembly and transport to the cell surface; as well as 2) the Ag binding capacity of the antibody genes used. The generation of hybrid MHC class II molecules with highly specific, non-MHC-restricted binding capacities will be useful for studying MHC class II-mediated effector functions such as selection of the T cell repertoire in thymus of transgenic mice.

Animals

Kindling and its consequences on learning in rats.

To study the learning performance of pentylenetetrazol- and amygdala-kindled Wistar rats we used the following learning tests: short-term memory was tested in the response-to-change model, brightness discrimination was tested in a Y-chamber, and two-way active avoidance learning was tested in a shuttle-box. Short-term memory was not impaired by both kindling procedures. Considering two-way active avoidance learning the performance of pentylenetetrazol (PTZ)-kindled rats was significantly diminished. This effect persists over a period of 4 weeks. However, amygdala (AMY)-kindled rats acquired this task like the controls. In brightness discrimination reaction (BDR) the learning performance of PTZ-kindled animals was not influenced. Although the acquisition of BDR was nearly identical, the 24-h retention was remarkably diminished in AMY-kindled rats. It was hypothesized that the different kindling procedures interfere in different ways and extent with neuronal circuits resulting in different functional impairments.

Amygdala

The effects of infraocclusion: Part 2. The type of movement of the adjacent teeth and their vertical development.

This second article discusses how the inclusion of a vertical component (the infraocclusion of the deciduous molar) into the otherwise horizontal band of transseptal fibers affects the vertical development of the two adjacent teeth. From the hypothesis proposed in the first article of this series, it seemed logical to assume that the occlusal heights of the teeth adjacent to the affected tooth would themselves be lowered, when measured to the inferior border of the mandible and compared with the height of the occlusal table of the control side. Secondly, since the vertical component affects only one side of each adjacent tooth, these teeth would be tilted about a center of rotation which is much higher (coronal) than is seen in a tooth that merely tips forward as the result of available space in the immediate vicinity in the arch. In this study, both these assumptions were confirmed, with a very high degree of statistical significance.

Bicuspid

The effects of infraocclusion: Part 1. Tilting of the adjacent teeth and local space loss.

The normal arrangement of the transseptal fibers in the dentition is one of a completely horizontal system that links the mesial and the distal aspects of each tooth within the dental arch, from the most distal tooth of one side to the most distal tooth of the other, across the midline. This continuous fiber band is parallel to the occlusal plane, being attached to each tooth coronal to the level of the interradicular alveolar bone crest and apical to the cementoenamel junction. Alteration of the occlusal plane will be mirrored by a similar change in the plane of the transseptal fiber system. From the clinical observation of young people with infraoccluded deciduous teeth, over many years, the regular and concomittant occurrence of certain other, well-defined phenomena appears to be the rule. It was thought that these phenomena could be explained in terms of the inclusion of a vertical component (infraocclusion) into this horizontal system. Two of these phenomena are discussed here. The first and most obvious of these relates to the exaggerated tipping that affects the adjacent tooth mesially and distally. The second parameter measures the amount of actual horizontal (mesiodistal) space change that occurs locally, within the dental arch, between the two teeth adjacent to the infraoccluded tooth, measured at both the occlusal level and at the level of their root apices. With a high degree of statistical validity, it was found that infraocclusion is related to severe tilting of the two adjacent teeth toward the affected tooth, with minimal space loss in the dental arch at the occlusal level, but a wide separation of root apices.

Ankylosis

The effects of infraocclusion: Part 3. Dental arch length and the midline.

The third and final article in this series examines the effect of infraocclusion on the midline of the mandibular dental arch. From clinical observation, a shift in the dental midline to the side affected by infraocclusion seemed very common, and this could be explained within the terms of the hypothesis proposed in the first article. A method was devised on a panoramic radiograph to define and to distinguish the anatomic (skeletal) midline and the dental midline. This confirmed the existence of a dental shift to the affected side. The hemiarch length of each side was measured on the film, from the distal of the second deciduous molar/second premolar to both constructed midlines, and was found to be longer on the affected side, confirming an abnormally distal position of the first molar on that side.

Ankylosis

Bioassay of a tracheal smooth muscle-constricting factor released by respiratory epithelial cells.

Epithelium-derived factors of unknown identity have been proposed to modulate airway smooth muscle tone. We developed a novel sensitive bioassay system that allows serial perfusion of cultured respiratory epithelial cells and guinea pig trachea (GPT). GPT responses were assessed as diameter changes by computerized video microscopy (resolution, 15 microns). A permanent hamster lung epithelial cell line was grown on microcarrier beads and perfused in a cell column. When the outflow tubing from the epithelial cell column was connected to the inflow cannula, the detector GPT contracted, reaching 28 +/- 6% of the maximum methacholine (100 microM)-induced contraction (n = 12, P less than 0.001). Perfusion of the cell column with diclofenac (10 microM) or lysin-mono-acetylsalicylic acid (100 microM) abolished the GPT contraction, whereas selective perfusion of the detector GPT with either agent did not block the contraction. Analysis of the effluent of the epithelial cell column demonstrated a significant basal release of prostaglandins F2 alpha and E2 (PGF2 alpha and PGE2) and 6-ketoprostaglandin F1 alpha, whereas only marginal amounts of thromboxane B2 were detected. When given exogenously, PGF2 alpha, PGE2, PGI2, and U-46619 all contracted the GPT. It is concluded that lung epithelial cells can contract GPT by releasing a transferable factor. This factor is likely to be a constrictor cyclooxygenase product that is not produced in epithelium-denuded GPT.

Animals

Mechanisms of loss of heterozygosity in retinoblastoma.

Retinoblastoma (RB) tumors arise when both alleles of the RB1 gene are inactivated by two mutational events (M1 and M2). M1 can be an initial germline or somatic mutation; M2 is frequently loss of heterozygosity (LOH), which makes the cell homozygous or hemizygous for the original mutation. LOH is the major mechanism by which many cancers are initiated. To further delineate the mechanism of LOH, we screened a total of 37 RB tumors for LOH by Southern blot analysis. The tumors were from 17 bilaterally and 17 unilaterally affected patients. Nineteen of 30 informative tumors (63%) from 27 patients showed LOH. Proximal and distal flanking markers on chromosome 13 were informative in 13 tumors, allowing evaluation of the mechanisms by which LOH occurred. Mitotic recombination was implicated in 6 (46%) of the 13 tumors.

Blotting, Southern

2-alpha-(N-dansyl-4-aminophenylthio)-N-acetyl-9-O-acetylneuraminic acid. A new specific and highly sensitive substrate in sialate-O-acetylesterase assay.

2-alpha-(N-Dansyl-4-aminophenylthio)-N-acetyl-9-O-acetylneuraminic acid (10) was prepared as a new specific and highly sensitively detectable sialate-9-O-acetyl-esterase substrate. It is built up from a sialidase-stable aminophenyl-alpha-thioketoside of N-acetylneuraminic acid. By labeling this thioketoside with dansyl chloride a fluorescent neuraminic acid derivative was prepared which allows determinations down to the picomol range. Regioselective acetylation with trimethylorthoacetate results in the corresponding 9-O-acetyl derivative. After incubation with esterase from bovine brain the hydrolysis products were separated on a HPLC column and fluorimetrically detected at 334 nm excitation and 564 nm emission. The Km value of 2.5 mM was in the range between the values of the completely unspecific methylumbelliferyl acetate and the less sensitively detectable N-acetyl-9-O-acetylneuraminic acid which have been used up to now as standard substrates.

Acetylesterase

Indication for the identity of palmoplantar keratoderma type Unna-Thost with type Vörner. Thost's family revisited 110 years later.

Palmoplantar keratoderma (PPK) type Unna-Thost is known to be the most common form of a hereditary disorder of keratinization of palms and soles. The disease is clinically identical with PPK type Vörner which is histologically characterized by epidermolytic hyperkeratosis. By reinvestigation of the family originally seen by Thost in 1880, the features of epidermolytic hyperkeratosis were found histologically confirming the diagnosis PPK of Vörner. This proves the identity of PPK type Thost with PPK of Vörner. Because of the histological variability of epidermolytic hyperkeratosis, detailed light and electron microscopic studies are necessary in cases of diffuse types of PPK.

Adult

[The potentiality of antero-posterior orthodontic extraoral traction: clinical and cephalometric results].

Heavy posterior orthopedic forces used for massive retropositioning of maxillary bone are among the orthopedic treatments preconised during mixed dentition. The clinical and cephalometric results of twelve cases treated by these means indicate that only dental movements can be obtained without the possibility of any orthopedic remodeling. These results corroborate those of other studies and it is possible to conclude that heavy orthopedic forces represent a very imprecise therapy which lead to side effects that are greater than the desired objectives.

Cephalometry

[The use of growth prediction and V.T.O.: special concepts].

Growth induces very important modifications of the skeletal positions of the maxilla and the mandible and the precise position of the teeth is not foreseeable before an attempt to evaluate the situation the bones will be in by the end of the treatment has been made. Predictability factors are examined and a specific construction of V.T.O. is suggested. Then a new superposition is proposed which allows to determine the direction and range of teeth displacements.

Cephalometry

[Pharmacokinetic aspects of a combination of metoclopramide and paracetamol. Results of a human kinetic study and consequences for migraine patients].

An open trial was carried out in eight healthy male and female volunteers to examine the bioavailability as well as the main kinetic parameters of Migränerton (metoclopramide and paracetamol; CAS 364-64-5 and CAS 103-90-2, resp). in comparison with reliable literature data. The results reported here clearly show that the absorption of both active ingredients from the fixed combination is complete and that therapeutically relevant plasma concentrations are achieved within 30 min. Bioavailability as well as tmax, t1/2, and time-lag are comparable with data resulting from reliable and internationally acknowledged kinetic studies. The fixed combination was shown to be kinetically compatible with regard to all parameters determined for metoclopramide and paracetamol.

Acetaminophen

Isolation of Drosophila genes encoding G protein-coupled receptor kinases.

G protein-coupled receptors are regulated via phosphorylation by a variety of protein kinases. Recently, termination of the active state of two such receptors, the beta-adrenergic receptor and rhodopsin, has been shown to be mediated by agonist- or light-dependent phosphorylation of the receptor by members of a family of protein-serine/threonine kinases (here referred to as G protein-coupled receptor kinases). We now report the isolation of a family of genes encoding a set of Drosophila protein kinases that appear to code for G protein-coupled receptor kinases. These proteins share a high degree of sequence homology with the bovine beta-adrenergic receptor kinase. The presence of a conserved family of G protein-coupled receptor kinases in vertebrates and invertebrates points to the central role of these kinases in signal transduction cascades.

Amino Acid Sequence

[Change in acylneuraminic acid content of T-lymphocytes and in plasma in breast cancer].

Increased sialic acid levels reflecting tumor burden are found on the surface of T-lymphocytes and in the plasma of patients with carcinoma of the mammary gland. The data of the determinations of sialic acid content and distribution on T-cells, using microanalytical methods such as HPLC and a colorimetric test, show that the total sialic acid content is increased by about 60% and that nearly 80-90% of the sialic acids consist of N-acetyl-9-O-acetyl-neuraminic acid, in comparison to the healthy controls (not containing O-acetylated neuraminic acid). Investigations on lymphocytes of malignant melanoma patients show similar changes of sialic acid content and distribution on the cell surface. Increased sialic acid levels are also found in the plasma of patients with cancer but no O-acetylated derivative can be found. Furthermore the examinations show that the separation of the T-lymphocytes from the total lymphocyte fraction is not required. Determination of sialic acids in the total lymphocyte fraction can be a simplification in carrying out further diagnostic investigations. A high level of sialic acids as "antirecognition factor" seems to be not only a marker of tumor cells but also an attribute of T-lymphocytes, involved in the defence against the malignoma (malignant melanoma, breast cancer). Considering the possible contribution of sialic acid to the immunoregulatory protective mechanism during the first stage of pregnancy, sialic acid content and distribution on T-cells of pregnant women are investigated. Both an increase and a change in the distribution of sialic acids can be excluded.

B-Lymphocytes

Gangliosides improve a memory deficit in pentylenetetrazol-kindled rats.

Epileptic patients often show impairments in a number of cognitive functions. Kindling is considered to be a useful experimental model for human epilepsy. Recently we have demonstrated a learning impairment in a shuttle box experiment in pentylenetetrazol (PTZ)-kindled rats. This model offers the possibility to investigate the relation between repeated convulsions and their consequences on learning and on the other side to test the effectiveness of substances on both processes. Although systemic application of gangliosides has neither an effect on the development of seizures induced by repeated injections of PTZ, nor on seizures induced by PTZ in kindled animals, the treatment protects against the memory-impairing effect of convulsions. These findings suggest a new useful strategy in the therapy of epileptic patients with the aim of diminishing the psychosocial problems in persons with seizure disorders: a combination of the anticonvulsive basic therapy and gangliosides.

Animals

Pharmacological effects on two inbred substrains of AB mice.

Mice of the two substrains AB/Gat and AB/Hal from the Jena AB inbred strain differ in behavior from each other by their aggressiveness occurring especially in the latter group after maturity. In order to ascertain the neurobiological background of aggressiveness, we injected mice of both substrains with either haloperidol, diazepam, or hexobarbital and measured their response on motor activity. In a second experiment, the reaction to a seizure evoking agent (pentylenetetrazol) was determined. Mice of both substrains were found to differ significantly in their reaction to haloperidol or diazepam injection. In contrast to that no changes in motor activity could be detected following hexobarbital administration. Animals of the aggressive AB/Hal substrain reacted more pronounced to pentylenetetrazol than those of the AB/Gat group. In conclusion, the varying aggressiveness of both AB mice substrains may be due to differences in dopaminergic and GABAergic neurotransmission.

Aggression

Pattern of NADPH-diaphorase active neurons in rat forebrain is unchanged after pentylenetetrazol kindling.

The activity of NADPH-diaphorase in rat telencephalic structures has been revealed by use of a histochemical method. Multiple neurons belonging to different nuclei were found to contain the enzyme. Furthermore, diaphorase reactive nerve fibres and terminal fields were observed to be widely distributed throughout rat brain. Chemical kindling induced by pentylenetetrazol (PTZ) did not effect the regional distribution and cellular localization of the enzyme in the rat CNS.

Animals

Poor development of outer dense fibers as a major cause of tail abnormalities in the spermatozoa of asthenoteratozoospermic men.

For a reasonable analysis of sperm motility, consideration should be given to the morphology of the flagellum. Among various tail disturbances, the present paper describes a structural shaft defect that is characterized by variations in diameter, poor outline and/or lacking endpiece. Electron microscopical examinations, especially the negative staining technique, have shown that in addition to membrane alterations there is one essential cause for the limited extension of the outer dense fibres. This disturbance may be of genetic origin or due to toxic or inflammatory influences. Further molecular biological studies are required to detect the actual cause of this defect, for which there is so far no adequate therapy.

Humans