[Giant cell tumor (osteoclastoma) of the humerus].
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Adult↗
Biomedical subjects
A Fröhlich
Publications and source records attributed to A Fröhlich.
High-performance liquid chromatographic assay for the determination of the novel podophyllotoxin derivative dimethylaminoetoposide (NK611) in human plasma.
A simple, rapid and reproducible plasma assay for the determination of the novel epipodophyllotoxin derivative, dimethylaminoetoposide (NK611, I) and its N-demethyl metabolite (II) is reported. The method involves solid-phase extraction using an isolute C18 cartridge and HPLC separation on a reduced-activity C18 column (8 cm long) with a mobile phase of acetonitrile-water-0.1 M phosphoric acid (23:76:1, v/v/v); peaks are detected at 205 nm. The intra- and inter-day precision and accuracy are within 5 and 4% for I and II, respectively. The sensitivity is 20 ng/ml for both I and II. The assay is applicable to clinical pharmacokinetic studies. In one cancer patient who received both an oral and an intravenous dose of 10 mg of I the bioavailability was 82% and the clearance 20.8 ml/min.
Antineoplastic Agents↗
Cell recognition during synaptogenesis is revealed after temperature-shock-induced perturbations in the developing fly's optic lamina.
Houseflies (Musca domestica) were exposed to pulses of heat (1 h) or cold (several hours) during early pupal life, and the effects were investigated on the development of the first optic neuropile, or lamina, of the visual system. The treatments were designed to perturb the cellular organization of the cartridges, the unit synaptic structures of the lamina, so as to provide novel synaptic opportunities among the normally fixed composition of these modules, thereby testing the preferences of their component cells during synaptogenesis. Various abnormalities were identified, but these were not always consistent between flies: retinal abnormalities included the loss and fusion of rhabdomeres, especially of the central cells of the ommatidium, whereas in the lamina low frequencies of abnormal cartridges were found. These included seven that were studied with serial sections, which instead of the normal pair of L1 and L2 monopolar interneurons had supernumerary cells of this type. The normal pairing of L1 and L2 at postsynaptic sites of receptor terminal tetrad synapses was preserved in these cases, the cells eschewing pairings of homologous L1/L2 or L2/L2 partners. This meant that more than one L1 could pair with a single L2 and vice versa, even at the same terminal, and appeared to do so opportunistically on the basis of proximity, with cells closer to each other pairing more frequently. Thus the cells behave during synaptogenesis as if they recognize other cells only as cell types (receptor, L1 or L2) and not as individual cells.
Animals↗
The irregular chiasm C-roughest locus of Drosophila, which affects axonal projections and programmed cell death, encodes a novel immunoglobulin-like protein.
The axonal projection mutations irregular chiasm C of Drosophila melanogaster comap and genetically interact with the roughest locus, which is required for programmed cell death in the developing retina. We cloned the genomic region in 3C5 by transposon tagging and identified a single transcription unit that produces a major, spatially and temporally regulated mRNA species of approximately 5.0 kb. Postembryonic expression is strong in the developing optic lobe and in the eye imaginal disc. The gene encodes a transmembrane protein of 764 amino acids with five extracellular immunoglobulin-like domains and similarity to the chicken axonal surface glycoprotein DM-GRASP/SC1/BEN. Both known irreC alleles reduce the level of transcription, whereas the roughestCT mutation disrupts the intracellular domain of the protein.
Alleles↗
Antisense effect of oligodeoxynucleotides with inverted terminal internucleotidic linkages: a minimal modification protecting against nucleolytic degradation.
The synthesis of a new class of antisense oligonucleotide compounds with 3'-3' and 5'-5' end inversion (INV-oligonucleotides) is described. Besides the advantage of simplicity of synthesis, physico-chemical studies show that these compounds do not disturb Watson-Crick base-pairing. INV-oligonucleotides have a half-life of 30 h in human serum. We show that they are capable of inhibiting SV40 large T-antigen expression in COS-1 cells, both in vitro and in vivo, and by modulation of the expression of cellular oncoprotein p53 in vitro.
Animals↗
Synthetic oligonucleotides for biomedical applications.
New developments of oligonucleotides for biomedical applications are surveyed. Diagnostic probes were conveniently labelled by enzymatic immunogenic tailing with 5-bromo-deoxyuridine triphosphate. "Antisense" oligonucleotides of potential therapeutic value were stabilized against nucleolytic decay by inversion of terminal internucleotidic linkages. Introduction of 2'-deoxy-2'-fluoro-nucleotide units enhances duplex stability and conveys resistance to ribonucleases.
Base Sequence↗
Analysis of a multiple-contact synapse missing a normally obligatory postsynaptic neuron: an electron microscopic study in the compound eye of Musca domestica.
In the compound eye of the adult female fly Musca domestica, photoreceptors form populations of multiple-contact output synapses, stereotypic in their architecture and in the identity of the four postsynaptic elements. Two postsynaptic elements, always originating from monopolar interneurons L1 and L2, lie side by side beneath the elongated presynaptic bar. Beneath each end of the bar, a further postsynaptic contact is located. These contacts most often are two processes either of amacrine cells or of epithelial glial cells. Monopolar cell L3 may be postsynaptic as well, with either an amacrine or a glial process completing the tetrad. To learn more about the factors determining connectivity and synaptic architecture, a three-dimensional reconstruction of serial electron microscopic sections was used to analyze a population of photoreceptor synapses at which one of the normally obligatory postsynaptic neurons, L1, was missing. In this abnormal case, the synapses make the normal four postsynaptic contacts in only 39% of the cases, otherwise making three (39%) or two (22%) contacts. Specificity of connectivity is preserved faithfully except that beta processes of T1 cells were postsynaptic at 2% of the synapses, where they do not normally contribute. In contrast to normal synapses, where amacrine and glial cell processes are mutual exclusive, such pairings could coexist in the aberrant synapse (27% of all synapses). All postsynaptic cells contributed the normal number of processes to a synaptic site, except for three synapses each with a supernumerary amacrine cell process. The postsynaptic cells therefore may be involved in regulating the number of their contacts made to a synaptic site.
Animals↗
[Basic stimulation--possibilities of activating support and care].
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Adolescent↗
High frequency of Ki-ras codon 12 mutations in pancreatic adenocarcinomas.
The frequency of Ki-ras gene mutations was studied in 100 paraffin-embedded sections obtained from 63 pancreatic adenocarcinomas by in vitro amplification of target sequences via polymerase chain reaction (PCR) and selective oligonucleotide hybridization. Forty-seven (75%) of the tumors contained a Ki-ras mutation at codon 12. No predominant amino acid substitution or nucleotide transition at this codon was observed. Two carcinomas exhibited 2 distinct Ki-ras mutations. No particular correlation could be established between the incidence of Ki-ras mutation and clinical parameters (sex, age, survival), tumor grade or tumor stage.
Adenocarcinoma↗
Direct connections between the R7/8 and R1-6 photoreceptor subsystems in the dipteran visual system.
Musca and related flies have three main photoreceptor subsystems. The R1-6 group has short axons that terminate in the cartridges of the first optic neuropile, the lamina. The cartridges are bypassed by the longer axons of R7 and R8, which run together to terminate at different levels in the underlying medulla neuropile. The present account describes a shallow, previously unidentified zone in the lamina within which R7/8 make glancing contact with R1-6. At the distal border of the cartridge over no more than 3-4 microns depth, the tangentially directed short axon of R6 squeezes between the pair from R7 and R8, forming quite large areas of mutual contact (approximately 7 microns2). Less frequently, R1 is contacted. At least some of these sites contain smaller membrane specialisations indistinguishable from the more numerous gap junctions found more proximally that interconnect the terminals of R1-6. The R7/8 junctions with R6 are of comparable size (0.15 micron 2) and likewise possess symmetrical membrane densities. They provide proposed pathways for direct electrical interaction to account for observed electrical input from R7/8 to the R1-6 subsystem. In two cases R7/8 was possibly postsynaptic to R1-6 at a multiple-contact synapse, but even if functional, these sites were so rare that they are unlikely to have much operational significance.
Animals↗
Acute myeloid leukemia: analysis of ras gene mutations and clonality defined by polymorphic X-linked loci.
In vitro DNA amplification and synthetic oligonucleotide hybridization was used to analyze 57 acute myelocytic leukemias (AML) for the presence of ras gene mutations. We demonstrated mutated alleles in 19% of primary AMLs (10/51) as well as in five of six secondary leukemias. Mutations occurred predominantly at N-ras codons 12, 13, or 61 (13 cases) and twice at Ki-ras codons 12 and 13. Ras gene mutations were preferentially associated with an M4 morphology according to the FAB (French-American-British) classification, but no particular correlation was observed with respect to clinical parameter (sex, age, course of disease) or immunophenotype and karyotype. Mutated ras alleles were absent in nine mutation-positive cases analyzed during remission. However, a more complex pattern emerged from the five patients analyzed in relapse exhibiting identical ras mutations in three cases, absence of a mutated allele in one patient, and acquisition of a N-ras mutation in yet another case, in which no mutation had been detected initially. Moreover, restriction fragment length polymorphisms (RFLP) of the X-chromosome genes hypoxanthine phosphoribosyl transferase (HPRT) and phosphoglycerate kinase (PGK) were studied in 19 of the AML patients. Nine cases (47%) were heterozygous for BglI or BamHI RFLPs at the PGK or HPRT loci, respectively, and therefore suitable for clonal analysis investigating X-chromosome inactivation. All of the patients exhibited a monoclonal leukemic cell population at presentation. In addition, five of seven cases studied in remission showed reemergence of a polyclonal pattern. However, two children exhibited persistence of monoclonal hematopoiesis despite complete clinical/hematological remission and a corresponding loss of a mutated ras allele in one of the patients. These data indicate the value of molecular genetic approaches for evaluation of the heterogeneous nature of remission and relapse in AML.
Adolescent↗
Review of studies with plasminogen concentrates and proposals for further therapeutic strategies with plasminogen concentrates.
Since the introduction of thrombolytic treatment based on the activation of plasminogen (PLG) by streptokinase (SK) and urokinase (UK) the search for new and improved methods has been continuing. The pivotal issue is how to achieve clot-specific fibrinolysis without producing systemic fibrinogenolysis. One out of various approaches to enhance lysis rates has been the use of PLG either alone or in combination with UK or SK in the light of the fact that fibrinolytic treatment, particularly using SK, is associated with a consumption of PLG, and that thrombi contain relatively small amounts of native PLG, however, are capable of incorporating added PLG in vitro. PLG-concentrates from various manufactures have been administered intravenously for treatment of deep venous thrombosis, mainly in combination with SK, and of pulmonary embolism in combination with UK. Local intracoronary and intraarterial administration in combination with UK has been reported in patients with myocardial infarction, and peripheral arterial occlusions, respectively. Lysis rates obtained in these studies were in most cases superior to results obtained with SK or UK alone, without increasing the incidence of bleeding complications. In addition, excellent results in larger group of patients with cerebral thrombosis were obtained with PLG alone. The encouraging results of these studies may be explained by the fact that all of the preparations used contained partially activated forms of PLG (commonly designated lys-PLG) to a greater or lesser extent. Lys-PLG has a higher affinity for fibrin than the native glu-PLG and is activated by UK or SK by a manyfold faster. These properties allow for a rapid formation of plasmin which--bound to fibrin--is also protected from the attack of neutralizing antiplasmin. The design and results of previous studies with lys-PLG concentrates will be reviewed and approaches to further improve fibrinolytic regimens with lys-PLG-concentrates discussed.
Fibrinolysis↗
Regulation of synaptic frequency: comparison of the effects of hypoinnervation with those of hyperinnervation in the fly's compound eye.
At the anterior rim of the first optic neuropile, or lamina, of the housefly's (Musca domestica) compound eye, the terminals of photoreceptors (R) innervate postsynaptic neurons in variable numbers to provide a continuous range of natural hypo- and hyperinnervations. Frequencies of photoreceptor synapses have been measured from quantitative electron microscopy on single sections of the lamina's unit synaptic modules, called cartridges. These are normally innervated by six photoreceptor terminals (6R cartridges). At the lamina's edge hypoinnervated cartridges (2R-5R) are found, whereas hyperinnervated cartridges (7R, 8R) are located at the equator between dorsal and ventral eye halves. In 2R cartridges each presynaptic terminal forms up to 1.5 times the normal, 6R cartridge number of synapses, thereby offsetting the reduced number of terminals and partially conserving the input upon the postsynaptic neurons. Thus the terminals have a reserve synaptogenic capacity never normally revealed. By comparison, terminals in 8R cartridges form about the same numbers of synapses as in "normal" eye regions, so that their postsynaptic neurons have a synaptic input increased by the extra number of terminals. The number of synapses formed between input terminals and target neurons is therefore not fixed but changes as a function of the total receptor terminal complement. The size of a photoreceptor terminal covaries to a certain extent with the number of its presynaptic sites; the spacing density of presynaptic sites over the terminals' surface in a 2R cartridge compared with an 8R cartridge increases far less (only 17%) than the increase in the number of sites (43%). The pair of postsynaptic cell interneurons in each 2R cartridge also shows a decrease in axonal diameter compared with those in 8R cartridges. Thus both the pre- and postsynaptic cells show size changes correlated with changes in their synaptic engagement.
Animals↗
Freeze-fracture study of an invertebrate multiple-contact synapse: the fly photoreceptor tetrad.
Bow-shaped particle arrays on the P-faces of the photoreceptor terminals R1-R6 in the lamina ganglionaris of the house fly represent the presynaptic sites of chemically mediated multiple-contact synapses (Shaw and Stowe, '82, Saint Marie and Carlson, '82). A particle array consists of two polar patches of regularly arranged particles and a central patch of irregularly arranged ones. Corresponding to these P-face arrays, the receptor E-faces have lattices of pits opposite the polar patches, and pits and some particles at the center. The presynaptic particle array corresponds in its dimensions to the electron-dense bar found in thin sections. The center-to-center spacing of the regularly arranged particles agrees with the spacing of striations found in the bar overlying the two polar elements of the postsynaptic tetrad. The elements in the two medial postsynaptic positions are hyperpolarizing monopolar cells L1 and L2, which show a strip of P-face particles within an otherwise bare postsynaptic membrane enclosed by a ridge, and a bare E-face. Comparison with other invertebrate synapses reveals two types of organization of postsynaptic membranes. IMPs fracture with the postsynaptic P-face in GABAergic and/or inhibitory synapses and with the E-face in glutaminergic and/or excitatory synapses; the fly photoreceptor synapse thus fits in the former category.
Animals↗
[Intraabdominal hemorrhage as an unusual complication of liver cirrhosis].
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Abdomen↗
Advancement of very severely handicapped children.
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Child↗
[Evaluation of results from the Landstuhl school experiment for the general development of severely handicapped children in schools for the physically handicapped].
The concept of integrated developmental intervention with profoundly disabled children has been evolved and tested in the school trial carried out at the Landstuhl Rehabilitation Centre Westpfalz. In its basic stage the intervention programme encompasses the availability of a good caring relationship between caregiver and child, with reliable satisfaction of needs and gentle child-centered care. This serves as a basis for systematic perceptual development by Basal Stimulation, movement development and initiation of communicative behaviour. The second stage in this developmental approach includes facilitation of continued growth of the children by experiencing concrete doing and meaning contexts. In line with the particular life situation of the parents and their children, parent involvement takes on a special dimension. Developmental intervention with profoundly disabled children presupposes the existence of an appropriate general framework.
Adolescent↗