Search PubMed⌕ Search

Biomedical subjects

C Zimmer

Publications and source records attributed to C Zimmer.

At least 199 records · Page 11Linked to original sources
PubMedDate not supplied

DNA binding properties of minor groove binders and their influence on the topoisomerase II cleavage reaction.

We present titrations of the human delta beta-globin gene region with DNA minor groove binders netropsin, bisnetropsin, distamycin, chromomycin and four bis-quaternary ammonium compounds in the presence of calf thymus topoisomerase II and DNase I. With increasing ligand concentration, stimulation and inhibition of enzyme activity were detected and quantitatively evaluated. Additionally we show a second type of stimulation, the appearance of strong new topoisomerase II cleavage sites at high ligand concentrations. The specific binding sites of the minor groove binders of the DNA sequence and their microscopic binding constants were determined from DNase I footprints. A binding mechanism for minor groove binders is proposed in order to explain these results especially when ligand concentration is increased.

Animals↗
PubMedDate not supplied

Molecular recognition between oligopeptides and nucleic acids: DNA binding selectivity of a series of 1,2,4-triazole-containing lexitropsins.

The synthesis of a series of 1,2,4-triazole-containing oligopeptide lexitropsins related to the natural antitumor antibiotic distamycin is described. The binding properties of these new agents to both native DNAs and synthetic polydeoxyribonucleotides were determined by UV absorption and circular dichroism studies. The DNA binding and sequence selectivity of these agents have been determined by complementary strand MPE footprinting on two restriction fragments of pBR322 DNA. The lexitropsins bearing one 1,2,4-triazole moiety bind to AT sequences like distamycin but also tolerate GC sites. However, 3, which contains two contiguous 1,2,4-triazole moieties, appears not to recognize AT stretches and demands two consecutive GC bases in the middle of a four-base recognition site. The triazole lexitropsins avoid ATTT (4264-4267) and AAAA (4273-4276) to which distamycin binds strongly to the EcoRI/Hind III fragment. Determination of pKa values indicates the 1,2,4-triazole units are protonated under physiological conditions. The avoidance of AT stretches and the recognition of GC base sites by 3 suggest molecular recognition in these cases is determined, not by electrostatic effects, but rather by invoking a hydrogen bond between the triazole 4-nitrogen and G-2NH2 in the minor groove.

Base Sequence↗
PubMedDate not supplied

Magnetic labeling of activated microglia in experimental gliomas.

Microglia, as intrinsic immunoeffector cells of the central nervous system (CNS), play a very sensitive, crucial role in the response to almost any brain pathology where they are activated to a phagocytic state. Based on the characteristic features of activated microglia, we investigated whether these cells can be visualized with magnetic resonance imaging (MRI) using ultrasmall superparamagnetic iron oxides (USPIOs). The hypothesis of this study was that MR microglia visualization could not only reveal the extent of the tumor, but also allow for assessing the status of immunologic defense. Using USPIOs in cell culture experiments and in a rat glioma model, we showed that microglia can be labeled magnetically. Labeled microglia are detected by confocal microscopy within and around tumors in a typical border-like pattern. Quantitative in vitro studies revealed that microglia internalize amounts of USPIOs that are significantly higher than those incorporated by tumor cells and astrocytes. Labeled microglia can be detected and quantified with MRI in cell phantoms, and the extent of the tumor can be seen in glioma-bearing rats in vivo. We conclude that magnetic labeling of microglia provides a potential tool for MRI of gliomas, which reflects tumor morphology precisely. Furthermore, the results suggest that MRI may yield functional data on the immunologic reaction of the CNS.

Animals↗
PubMedDate not supplied

Cerebrospinal fluid indices in cryptococcal and tuberculous meningitis: the spider web coagulum and its diagnostic significance.

The differentiation between a chronic cryptococcal meningitis and a chronic tuberculous meningitis may cause problems for the clinician only if standard microbiological methods are not applied to the diagnosis of both infections. In a male non-AIDS patient (50 y), 11 years after a suggested diagnosis of "tuberculous meningitis", meningoencephalitis with hydrocephalus was diagnosed and treated accordingly without success. Mycobacterium tuberculosis was never found. Because fibrin fibres of a spider web coagulum in the CSF resembled Aspergillus mycelium, the patient was then treated with amphotericin B + flucytosine. Finally, a mycological examination led to the true diagnosis: (1) In the CSF, resembling Aspergillus hyphae were found to be spider web coagulum fibres. (2) Cryptococcal meningoencephalitis based on the detection of Cryptococcus neoformans in CSF and its antigen in serum and CSF. - At post-mortem, cryptococcal meningoencephalitis was established as cause of death. Residual signs of tuberculosis could not be detected in the brain and the meninges. Common clinical similarities of cryptococcal and tuberculous meningitis and the possibility of a double infection are discussed. A comparison of the presence of Cr. neoformans in the meninges of non-AIDS and AIDS patients is made. The formation of spider web coagulum in the CSF is discussed. Proposals for the diagnosis, therapy and prophylaxis of cryptococcal meningitis are made.

Cryptococcosis↗
PubMedDate not supplied

[Effect of DNA local conformation on the affinity and binding specificity of bis-netropsins to DNA].

The interaction of short nucleotide duplexes with bis-netropsins, in which netropsin fragments are linked in the tail-to-tail orientation via cis-diammineplatinum group (<--Nt-Pt(NH3)-Nt-->) or aliphatic pentamethylene chain (<--Nt-(CH2)5-Nt-->), has been studied. Both the bis-netropsins have been shown to bind to DNA oligomer 5'-CCTATATCC-3' (I) as a hairpin with parallel orientation of netropsin fragments in 1:1 stoichiometry. Monodentate binding has been detected upon binding of bis-netropsins to other duplexes of sequences 5'-CCXCC-3'--where X = TTATT (II), TTAAT (III), TTTTT (IV), and AATTT (V)--along with the binding of bis-netropsins as a hairpin. The formation of dimeric antiparallel motif between the halves of two bound bis-netropsin molecules has been observed in the complexes of <--Nt-(CH2)5-Nt--> with DNA oligomers IV and V. The ratio of binding constant of bis-netropsin as a hairpin (K2) to monodentate binding constant (K1) has been shown to correlate with the width and/or conformational lability of DNA in the binding site. The share of bis-netropsin bound as a hairpin decreases in the order: TATAT > TTATT > TTAAT > TTTTT > AATTT, whereas the contribution of monodentate binding rises. The minimal strong binding site for <--Nt-Pt(NH3)-Nt--> and <--Nt-(CH2)5-Nt--> binding as a hairpin has been found to be DNA duplex 5'-CGTATACG-3'.

Anti-Bacterial Agents↗
PubMedDate not supplied

Immuno-lectin histochemistry and ultrastructure in two cases of globoid cell leukodystrophy (Krabbe's disease).

Two cases of globoid cell leukodystrophy (Krabbe's disease) have been studied by means of conventional histological, immunohistochemical and ultrastructural methods. Lectins specific for several different carbohydrates, Ricinus communis (RCA-1), peanut agglutinin (PNA), wheat germ agglutinin (WGA) and Concanavalin A (Con A) have been utilized both at optical and ultrastructural level. In both cases a strong positive labeling of the globoid cells could be observed light-microscopically. Ultrastructurally immunogold deposits only of RCA-I and WGA in the typical Krabbe's inclusions have been clearly demonstrated.

Acetylgalactosamine↗
PubMedDate not supplied

Status epilepticus as a risk factor for postencephalitic parenchyma loss evaluated by ventricle brain ratio measurement on MR imaging.

BACKGROUND AND PURPOSE: Cerebral atrophy following herpes simplex encephalitis has formerly been described. We aimed to quantify atrophy after encephalitis of various causes. Additional objectives were to define which initial or long-term clinical factors correlate with volume loss and to search for any correlate in global clinical outcome measures. METHODS: MR imaging was performed in 40 subjects in the acute stage of encephalitis and > or =6 months after onset of symptoms. The ventricle brain ratio (VBR) was measured on corresponding images from disease onset and follow-up, and the change in VBR (VBR delta) was calculated as a percentage value of the starting measure. Clinical outcome was evaluated by interview and neurologic examination and characterized by using an encephalitis-adapted version of the modified Rankin Scale. RESULTS: The VBR delta ranged from -5%-102% (median, 5.93%; lower quartile, 1.8%; upper quartile, 14.55%; mean, 14.43%; SD, 23.75%). We found significant differences in the VBR delta between those patients who required intensive care (P = .027), had more than 2 epileptic seizures or a status epilepticus during the acute stage (P = 0.021), or developed postencephalitic epilepsy (P = .015) and their respective counter-subgroups. Three patients were rated to have unfavorable outcome (modified Rankin Scale, 3-5). Patients with unfavorable clinical outcomes tended to show greater VBR delta values, but a statistical evaluation was impossible because of small numbers. CONCLUSION: More than 2 epileptic seizures or a status epilepticus during the acute stage of encephalitis is associated with a greater loss of parenchyma.

Acute Disease↗
PubMedDate not supplied

Light microscopic and ultrastructural study on CNS lesions in infantile Gaucher's disease.

We report on the light microscopic and ultrastructural CNS findings and the clinical course in a boy with infantile Gaucher's disease who died at 6 1/2 months. Besides the morphological alterations described in the literature, like perivascular Gaucher cells and nerve cell loss, our case was characterized by an unusually extensive proliferation of GFAP-positive astrocytes in the vicinity of stored material but also in regions where no storage was detected. Electron microscopy revealed massively enlarged lysosomes in the storage cells. The lysosomes showed twisted tubular structures, some of them penetrating the outer membrane. Isolated tubules were found to lie free in the cytosol. These tubules correspond to stored crystallized glucocerebroside molecules, which are most stable in this twisted arrangement.

Astrocytes↗