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A Fröhlich

Publications and source records attributed to A Fröhlich.

At least 19 recordsLinked to original sources
PubMed2001

A scanning electron-microscopic study of apical contacts in the eye during postembryonic development of Drosophila melanogaster.

The apical surface of the ommatidium plays a major role during development of the compound eye. Cell-cell contacts leading to induction seem to be initiated at this surface. The pupal eye of Drosophila was examined, using scanning electron microscopy, from a few hours after eversion of the imaginal disc (19 h after pupariation, 25 degrees C) until shortly after the onset of the corneal secretion (46 h after pupariation, 25 degrees C). At 19 h, the primary pigment cells are in the process of encircling the cone cells. At this time, tufts formed by the cone cell microvilli are the most prominent feature of the eye's surface. Shortly thereafter, the interommatidial cells become more prominent. Their surfaces are raised to form ridges that enclose primary pigment cells and cone cells. From 21 h onwards and lasting for 5-6 h, the interommatidial cells form slim cytoplasmic extensions that spread over the surfaces of the surrounding cells. These extensions contact neighbouring interommatidial or primary pigment cells, but also non-adjacent cells such as cone cells. The fates of these interommatidial cells presumably are determined during that time. The cell-cell interactions may play a role in determining cell fates, for example by providing positional information.

Animals↗
PubMed2000

Neurite morphogenesis of identified visual interneurons and its relationship to photoreceptor synaptogenesis in the flies, Musca domestica and Drosophila melanogaster.

The first neuropile, or lamina, of the fly's optic lobe comprises a model set of identified neurons that are arrayed in cylindrical modules, called cartridges. The cartridge acquires adult form only in the second half of the fly's pupal life. All cells are by then correctly located within each of the lamina's cartridges (Drosophila, Musca), becoming invested by glial cells after 75% of pupal development (P + 75%). In adult cartridges, two lamina cells, L1 and L2, receive input from photoreceptor terminals R1-R6, at so-called tetrad synapses that form in the pupa when these cells' dendrites contact R1-R6. Single-section electron microscopy (EM, Drosophila) and serial-EM reconstructions of L1 and L2 (Musca) reveal relationships between the morphogenesis of L1/L2 dendrites and the formation of tetrads. Neurite outgrowth is initially (P + 55%) random and neurites are unbranched; many neurites invaginate surrounding terminals of R1-R6 but, later, embrace the outer surfaces of these. The maximum profusion of neurites at P + 74% coincides with peak numbers of nascent tetrads; neurites then branch vertically, in the lamina's depth. Later, neurites failing to reach R1-R6's outer surfaces regress. Down the length of their axons, L1 and L2's neurites initially form a random sequence, L1 partnering L1 as often as L2, etc., but beginning at P + 74%, L1 partners L2, and L2 partners L1, with progressive strictness. L1 has more neurites overall than L2. These observations are consistent with the following hypotheses: a neurite only survives if it contacts a presynaptic site; a synapse only survives if it progressively acquires the appropriate number and combination of postsynaptic neurites, culminating in a tetrad; an interaction exists between the neurites of L1 and L2, so that the growth of one respects the pattern of growth of the other.

Animals↗
PubMed1999

Detection of liver metastases from pancreatic cancer using FDG PET.

UNLABELLED: We evaluated the potential of the glucose analog [18F]fluorodeoxyglucose (FDG) as a PET tracer for the hepatic staging in 168 patients designated for resective pancreatic surgery. METHODS: Metastatic liver disease was confirmed or excluded during surgery or with CT follow-up for at least 6 mo. Proven metastases were then retrospectively identified on preoperative CT (gold standard). Hepatic PET scans of all patients were interpreted blindly. Any focal FDG uptake was considered malignant. Both proven hepatic metastases and suspicious hepatic PET lesions were then compared, lesion by lesion, with CT. Standardized uptake values (SUV) and tumor-to-liver ratios (T/L) were determined for the most intense lesion of each patient. RESULTS: Sensitivity of FDG PET was 68% (15 of 22 patients). The lesion detection rate was 97% (28 of 29 metastases) for lesions >1 cm and 43% (16 of 37 metastases) for lesions < or = 1 cm. Specificity was 95% (138 of 146 patients). Six of eight patients with false-positive results had marked intrahepatic cholestasis (versus 3 of 15 patients with true-positive lesions), one had an infrahepatic abscess and one had a right basal pulmonary metastasis. The SUV and T/L were 4.6+/-1.4 and 2.3+/-1.1, respectively, for malignant lesions and 4.1+/-1.5 and 1.9+/-0.3, respectively, for false-positive lesions and therefore are of limited value. CONCLUSION: FDG PET provides reliable hepatic staging for lesions >1 cm. False-positive results are associated with the presence of marked intrahepatic cholestasis. For lesions < or = 1 cm, FDG PET can define malignancy in 43% of suspicious CT lesions in the absence of dilated bile ducts.

Aged↗
PubMed1994

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1988

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↗
PubMed1987

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↗