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Biomedical subjects

A Franke

Publications and source records attributed to A Franke.

At least 145 records · Page 8Linked to original sources

Thiol-proteindisulfide-oxidoreductase (proteindisulfide isomerase): a new plasma membrane constituent of mature human B lymphocytes.

The thiol-proteindisulfide-oxidoreductase (TPO, EC 1.8.4.2., proteindisulfide isomerase, EC 5.3.4.1.) is known as an cytoplasmatic enzyme, and is thought to be involved in the post-translational folding of disulfide containing proteins. Using monoclonal and polyclonal antibodies the authors were able to prove that this enzyme or an unknown homologous protein is localized also to the plasma membrane of B lymphocytes. In peripheral blood from healthy donors 11% of the mononuclear cells (PBMNC) expressed this surface antigen whereas in PBMNC of patients with B-cell chronic lymphocytic leukaemia 76% of the MNC were positive. This value correlates well with the known B-cell markers CD19 and CD20. However, this antigen is different from all known clustered B-cell markers. Immunoprecipitation analysis of PHA-stimulated PBMNC and of cells from patients suffering from chronic lymphocytic leukaemia revealed a membrane protein with the same molecular weight (61 kDa) as the TPO. These data suggest that this enzyme is present not only in the cytoplasm but also on the surface of B cells and that it is possibly involved in the regulation of the SH-SS status of the cell membrane proteins of B lymphocytes.

Adult↗

A synthetic C22 carotenoid inhibits carcinogen-induced neoplastic transformation and enhances gap junctional communication.

In 10T1/2 cells several dietary carotenoids have previously been shown to be capable of inhibiting carcinogen-induced neoplastic transformation. Two synthetic novel compounds, a C22 carotenoid, C22-polyene-tetrone-diacetal, and a C28 carotenoid, C28-polyene-tetrone, have now been tested in this system. The C22 compound was active in completely inhibiting 3-methylcholanthrene-induced transformation at 10(-5) M when added during the post-initiation phase of carcinogenesis. Gap junctional intercellular communication was strongly upregulated at this concentration. This activity has previously been shown to be highly correlated with, and has been proposed to be mechanistically linked to, inhibition of transformation by carotenoids in 10T1/2 cells. In contrast, the C28 compound, previously reported to be more active as a singlet oxygen quencher than C22, did not demonstrate activity in 10T1/2 cells in either assay system. This lack of activity was not due to chemical instability or lack of cellular uptake: the C28 compound was more stable in cell culture medium over 7 days and achieved higher cellular levels than the C22 compound (5 x 10(-11) mol/10(6) cells versus 0.5 x 10(-11) mol/10(6) cells). The activity of the C22 compound was not due to toxicity, since transformation occurred in carcinogen-treated cultures after its removal; neither was it due to antiproliferative effects on transformed cells, since the C22 compound did not prevent focus formation by transformed cells in reconstruction experiments. The demonstration that synthetic carotenoids possess biological activities comparable to the most potent naturally occurring compounds suggest that rational synthesis of compounds with improved pharmacological properties should be possible.

Acetals↗

Polycomb and polyhomeotic are constituents of a multimeric protein complex in chromatin of Drosophila melanogaster.

The polycomb group (Pc-G) genes are responsible for maintaining the repressed state of homeotic genes during development. It has been suggested that the Pc-G exerts its transcriptional control by regulating higher order chromatin structure. In particular, the finding of genetic and molecular similarities to components involved in heterochromatin formation, led to the proposal that homeotic genes are permanently repressed by mechanisms similar to those responsible for heterochromatin compaction. Because of synergistic effects, Pc-G gene products are thought to act in a multimeric complex. Using immunoprecipitation we show that two members of the Pc-G, Polycomb and polyhomeotic, are constituents of a soluble multimeric protein complex. Size fractionation indicates that a large portion of the two proteins are found in a distinct complex of molecular weight 2-5 x 10(6) Da. During embryogenesis the two proteins show the same spatial distribution. In addition, by double-immunofluorescence labelling we can demonstrate that Polycomb and polyhomeotic have exactly the same binding patterns on polytene chromosomes of larval salivary glands. We propose that some Pc-G proteins act in multimeric complexes to compact the chromatin of stably repressed genes like the homeotic regulators.

Animals↗

A short multilingual quality of life questionnaire--practicability, reliability and interlingual homogeneity.

International cooperative clinical trials require a multilingual quality of life questionnaire. The 'International Society for Chemo- and Immunotherapy' therefore designed a study to develop and test a 'health accentuated' quality of life questionnaire in the eight languages spoken in this society. The objective was to examine practicability, reliability and interlingual homogeneity. Versions of the questionnaire in Czech, German, Hungarian, Italian, Kroatian, Polish, Romanian and Slovakian have been prepared. The results are based on data of 1,104 adult patients. They demonstrate that the developed questionnaire is practicable. Patients need 10-15 min to answer it, usually without assistance. The proportion of missing values is for all but two questions less than 3%. The questionnaire also found high acceptance reflected by only 2.7% refusals. It is reasonably reliable in each language. Interlingual homogeneity could be shown by demonstration of strong structural similarities between the different versions using multidimensional scaling, factor analysis and comparison of mean profiles.

Adolescent↗

Analysis of the functional role of the Polycomb chromo domain in Drosophila melanogaster.

The chromo domain was identified as a homologous protein motif between Polycomb (Pc)--a member of the Pc-group genes encoding transcriptional repressors of the homeotic genes--and HP1--a heterochromatin-associated protein encoded by the suppressor of position effect variegation gene Su(var)205. Together with previous genetic studies, this molecular similarity supports the suggestion of a common mechanism used for generating heterochromatin and for repressing homeotic genes. The evolutionary conservation of the chromo domain throughout the animal and plant kingdoms implies an important functional role for this protein motif. We have used transgenic lines as well as transient expression assays employing Drosophila tissue culture cells to study the functional role of the Pc chromo domain. Wild-type Pc protein is endogenously expressed in SL2 cells and is found in large immunologically visible complexes. Mutated Pc proteins were expressed as Pc-beta-galactosidase fusion proteins, and their nuclear distribution was examined by indirect immunofluorescence in tissue culture cells and on polytene chromosomes of transgenic larvae. We show that carboxy-terminal truncations of the Pc protein do not affect chromosomal binding of the fusion protein. However, mutations affecting only the chromo domain including in vitro generated deletions, as well as point mutations, abolish chromosomal binding. Our results demonstrate for the first time that the chromo domain is important for the function of Pc and that it is absolutely required for binding of Pc protein to chromatin. Some of the nuclear patterns generated by the mutated forms of the fusion proteins suggest, furthermore, that the chromo domain could be involved in a packaging mechanism, essential for compacting chromosomal proteins within heterochromatin or heterochromatin-like complexes.

Alleles↗

Complicated duodenal ulcer, vagotomy or distal resection--own experience.

An analysis of clinical material through 10-year-period (1980-1989) is presented. There were 708 gastric operations performed for gastroduodenal ulcer disease. Most frequently distal gastric resections (585) were used, 233 in B. I. and 352 in B II. modification. Selective proximal vagotomy (SPV) was less frequently used (only 116 cases). Authors think there is no reason for a general use of SPV for each form of duodenal ulcer because of very serious competition with the H2 blockers. A different individual proved choice of the method as well as an appropriate subtle operating technique is considered to be essential.

Duodenal Ulcer↗

[Characterization of T lymphocyte defects in patients with Hodgkin's disease using enzyme chemical markers].

Patients suffering from lymphogranulomatosis were studied with respect to cellular immune deficiencies. For this purpose, mononuclear cells from venous blood were separated and subjected to analysis of lymphocyte markers. T-lymphocytes were enumerated by means of the sheep erythrocyte (SE) rosette test. T cell subpopulations were determined using enzyme cytochemical staining for dipeptidyl peptidase IV (DP IV) and unspecific acid alphanaphthylacetate esterase (ANAE). In 18 patients with M. Hodgkin a significant reduction in the T lymphocyte count in peripheral blood was found. This T cell defect is due to a selective decrease in the TM-subpopulation as identified by enzyme cytochemical markers DP IV and ANAE (focal reaction). From these results it is concluded that patients with lymphogranulomatosis have characteristic abnormalities in the immune system in the sense of a disturbed equilibrium of immune regulatory cells.

Adult↗

Electrostimulation of healing abdominal incisional hernias by low frequency, bipolar, symmetrical rectangular pulses. An experimental study.

A total of 107 male Wistar rats had abdominal hernias repaired (3 weeks after they had been artificially induced) by a two layer closure of the abdominal wall--the Mayo technique. The wounds of 56 rats were subjected to constant stimulation by an electric flow field. An implanted stimulation unit provided a low frequency (0.87 Hz), bipolar, symmetrical rectangular pulsed current (+/- 25 microA). A control group were given units that did not transmit current. In 39 of the 51 animals in the control group the muscle margins of the abdominal scars separated by between 1 and 5 mm. The scars of the electrostimulated animals were distinguished histologically by early formation of fibroblasts and deposition of collagen and the rapid maturation and longitudinal alignment of the collagen fibres. 46 of 56 of these scars were not separated. This technique may have a clinical application as adjuvant treatment for relapses of incisional hernias.

Abdominal Muscles↗

[Bipolar impulses or direct current as an adjuvant treatment of incisional hernia? Comparative experimental animal study].

The electrostimulation of the cicatricial healing in the abdominal wall were tested in 119 Wistar rats by means of bipolar rectangularly pulsed current (0.87 Hz, +/- 25 mu A) and direct current (1 mu A). Doubling of the fascia of an abdominal wall hernia was carried out in three groups of rats. In the first group the operational region was stimulated by rectangularly pulsed current, strong proliferated cicatrices were formed with premature production of fibroblasts and collagenous fibres, fast maturation, and high strength. In the second group it was stimulated by direct current, a less exact longitudinal orientation of the collagenous fibres and a slower cicatricial maturation were shown. The third group applied as a control showed a cicatricial distension up to 5 mm. The electrostimulation of the proliferation of connective tissue and cicatricial healing could be pointed out between different tissues (peritoneum and fascia).

Animals↗

[Retinopathic visual loss in hemorrhagic necrotizing pancreatitis].

Pancreatic retinopathies have been described with reference to case histories since 1975. Descriptions differed greatly from each other with regard to onset, development, and residual vision along with impairment. Two of the author's own cases are reported in this paper. Agreement with pathological patterns published elsewhere (alcohol-related genesis, age) are compared to points of difference (juncture of manifestation, final condition). Aetiology has proved to be of multifactorial nature, with presence and involvement of fat embolism or granulocyte aggregation being possible. Reference is made to elements with relevance to prognosis. The demand is made for no-delay treatment and routine checks.

Acute Disease↗

[Treatment of plasmacytoma with hyperviscosity syndrome].

It is reported on the treatment of three patients with a hyperviscosity syndrome in IgG-plasmocytoma. Before every polychemotherapy cycle a plasma exchange was carried out, when the total protein in the serum and the immunoglobulins were essentially increased and clinical symptoms of the hyperviscosity syndrome were existing. The results and the possible effects on the efficacy of the therapy with cytostatic agents are discussed. In the light of our experiences we can recommend the membrane plasma filtration treatment as symptomatic therapeutic measure in the hyperviscosity syndrome.

Aged↗

[Computerized tomography of the mediastinum--results of a retrospective study].

The results of the CT-investigations of the mediastinum on 500 patients can be described in the following way: the assessment of mediastinal lymph nodes was clearly improved by the CT. About half the positive mediastinal findings in malignant lymphomas was to be proved only in the CT. The diagnostics of mediastinal space-occupations was elevated to a higher degree. Statements concerning the coarse tissue are possible. In myasthenia gravis pseudoparalytica the computed tomography is the best method for demonstrating the morphologic relations. The individual changes of the thymus gland are, however, not certainly to be differentiated from each other. Among the vascular changes aneurysms and an arcus aortae dexter with right descending thoracic aorta can unequivocally be demonstrated. A particular advantage of the computer tomography consists in the possibility to separate the perfused lumen from the thrombotically closed one. The search for a primary tumour in the mediastinum is not useful in negative conventionally radiographic findings.

Aortic Aneurysm↗

Tricyclic epines. Novel (E)- and (Z)-11H-dibenz[b,e]azepines as potential central nervous system agents. Variation of the basic side chain.

The synthesis and pharmacological activity of new (E),(Z)-[6-(alkylamino)-11H-dibenz[b,e]azepin-11- ylidene]acetonitriles 12-45 and (E),(Z)-[6-(aminoalkoxy)-11H-dibenz[b,e]azepin-11-ylidene] acetonitriles 46-51 are described. The introduction of the cyanomethylene group into the 11-position of the 11H-dibenz[b,e]azepine framework has been carried out by a Wittig-Horner reaction under mild conditions. The (E),(Z) isomers were separated by fractional crystallization, assignment being achieved by X-ray analysis. A number of (E),(Z)-[6-(alkylamino)-11H-dibenz-[b,e]azepin-11-ylidene] acetonitriles (12, 14, 16, 20) show potent neuroleptic activity (2-7 times that of clozapine) in animal tests. The screening included tests for sedative and anticholinergic activity in mice, apomorphine and tryptamine antagonism in rats, and muscle-relaxing activity in rabbits. The divergence in the activity profile in the case of the separated (E),(Z) isomers has been observed as an interesting new aspect: the (Z) isomers show a significantly higher sedative and muscle-relaxant activity, whereas the (E) isomers possess a higher anticholinergic efficacy and somewhat greater apomorphine antagonism. Broad changes in the basic side chain were made in order to investigate structure-activity relationships. The important geometrical parameters for the molecules, obtained by X-ray analysis, were compared with the corresponding features in dopamine agonists and antagonists.

Animals↗

Dipeptidyl peptidase IV in human T-lymphocytes: cytochemical and histochemical investigations in patients with non-Hodgkin's lymphoma.

The occurrence of DP IV-reactive T-lymphocytes in patients with aleukemic non-Hodgkin's lymphoma (NHL) was studied using mononuclear cells (MNC) obtained from peripheral blood, bone marrow aspirates and lymph nodes, as well as cryostat sections of lymph nodes. These patients were found to have a reduced percentage of DP IV-reactive T-cells in MNC from peripheral blood (32%) in comparison to a healthy control group (44%). Patients suffering from chronic lymphocytic leukemia (B-type CLL) also had significant reduced level of DP IV-reactive cells (5% DP IV-reactive cells in the MNC fraction corresponding to about 40% of the T-cell fraction) in peripheral blood, whereas in lymph nodes of these patients 72% of the T-cells expressed DP IV. Among the MNC from lymph nodes of patients with aleukemic NHL about 24% were DP IV positive corresponding to 57% of the T-cell fraction. MNC from bone marrow of these patients were shown to contain about 21% T-lymphocytes and 18% DP IV-reactive cells. In addition to that, cryostat sections of lymph nodes were analysed for the occurrence and distribution of DP IV. In normal lymph nodes and tonsils DP IV-positive cells have the same distribution pattern like T-cells in general. In lymph node sections from patients with NHL of B-cell origin, such as B-CLL, the DP IV-reactive cells are sparsely and irregularly distributed and displaced by the proliferating B-cells. It is concluded that DP IV is a useful marker not only for T-lymphocytes in proliferating lymphatic tissue but also an indicator of imbalances between regulatory T-cell subsets in peripheral blood.

Bone Marrow↗

[Non-Hodgkin lymphoma (NHL) as a primary finding in the central nervous system].

The clinical picture is dealt with on the basis of seven cases of primarily recognised non-Hodgkin's lymphomas in the CNS treated by us. Because of the frequently serious initial situation immediate surgical intervention can on the one hand improve or remove the paralysis and, on the other, it will lead to histological diagnosis. Elderly patients with a lower degree of malignity show a better prognosis.

Humans↗