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Biomedical subjects

C Zimmer

Publications and source records attributed to C Zimmer.

At least 127 records · Page 7Linked to original sources

Cytokeratin expression in a congenital multipotential primitive neuroectodermal tumor.

A case of an uncommon congenital primitive neuroectodermal cerebellar tumor (PNET) in a 5-month-old child is reported. After subtotal surgical resection, the residual tumor did not respond to radiation and chemotherapy. Histologically, the tumor was composed of small, round, undifferentiated cells and several other patterns like astrocytomatous, oligodendrogliomatous, and ependymomatous structures. Immunostaining was positive for most of the cells for vimentin and S 100, fewer were positive for glial fibrillary acid protein (GFAP) and neuron-specific enolase, and only a few for synaptophysin. Surprisingly, the tumor showed strong expression of several monoclonal cytokeratins (CK) with different molecular weights, together with epithelial membrane antigen. Furthermore, we found a coexpression of the tumor cells for CK and vimentin, while CK-GFAP and CK-S 100 were negative. Ultrastructurally, intracytoplasmic intermediate filaments could be observed corresponding to immunohistochemical CK expression. The very strong CK and vimentin expression in this case was interpreted as a sign of the embryonic nature of the tumor.

Biomarkers, Tumor↗

Type 2a fibre rhabdomyolysis in myoadenylate deaminase deficiency.

A 31-year-old woman developed an acute, potentially fatal rhabdomyolysis of undetermined origin. Muscle biopsy revealed selective lysis involving exclusively type 2a fibers. Myoadenylate-deaminase (MAD) deficiency was proven by a negative histochemical reaction as well as by an enzymatic biochemical determination. The significantly greater energetic dependence of type 2a fibres on MAD explains their selective damage. The patient's mother also suffers from a similar muscle disease of still unclarified origin.

AMP Deaminase↗

Oxalate-induced encephalitis after infusions of sugar surrogates.

The case of a 55-year-old female with oxalate-induced lethal encephalitis following infusions of sugar surrogates is reported. Renal failure and subsequent central coma developed following the use of xylitol, fructose and sorbitol above the recommended dosages. The patient died due to raised intracranial pressure. Cerebral damage was caused by encephalitis due to calcium oxalate crystals. Oxalosis induced by sugar surrogates may be explained either by dose-dependent toxic effects or genetically fixed intolerance.

Biopsy↗

Altered glial fibrillary acidic protein immunoreactivity in rat brain following chronic hypoxia.

Glial fibrillary acidic immunoreactivity in brain was examined in normal animals and in rats subjected to chronic hypoxia. Animals were exposed to a chronic normobaric adaptive hypoxia with decreasing amounts of oxygen (finally 6%) for a period of 59 and 114 days, respectively. In paraffin-embedded sections the glial fibrillary acidic protein immunoreactivity in normal and hypoxic animals was examined at three coronal levels. A mild glial fibrillary acidic protein immunoreactivity in the perivascular glial layer, external glial limitans membrane and periventricular astrocytes, as well as in some areas of hippocampus and cerebellum, was noted in normal animals. Chronic hypoxia for 114 days resulted in a marked increase of glial fibrillary acidic protein immunoreactivity in dentate gyrus of hippocampus, Bergmann glia of the cerebellum, internal capsule and pyramidal tract. On the other hand, the glial fibrillary acidic protein activity following 59 days hypoxic exposure was almost the same as controls. These results show that systemic deep chronic hypoxia (depending on the intensity and the duration) activates the endogenous expression of glial fibrillary acidic protein in astrocytes of specific brain regions. The probable significance of this finding is discussed.

Animals↗

[Sudden blindness in an AIDS patient. Simultaneous infection with cytomegalovirus and herpes simplex viruses and development of malignant non-Hodgkin lymphoma].

A 50 year old patient with non-diagnosed HIV-infection at onset of his illness developed impairment of vision and temporary double vision combined with severe hemianopsia. With normal fundus and suspicious Herpes simplex iritis therapy with Acyclovir was started. Primarily the patient showed a good response to the therapy and loss of vision could be prevented. After 4 weeks CMV-retinitis developed. In spite of Gancyclovir therapy manifestation of total loss of vision after 6 weeks. Autopsy demonstrated signs of simultaneous a CMV-infection of the retina and a herpes simplex-infection of the optic nerve combined with a Non-Hodgkin-Lymphoma of the optic tract.

Acquired Immunodeficiency Syndrome↗

Strategy for diagnosis of Toxoplasma gondii in stereotactic brain biopsies.

The colloidal gold method using polyclonal antitoxoplasma antibodies was used to detect Toxoplasma organisms in stereotactic brain biopsies of patients with AIDS. For comparison, conventional histologic staining and additional other immunohistochemical methods were also studied in the same cases. Compared to the other stains, a reliable diagnosis of Toxoplasma gondii could be established with the colloidal gold method in all patients investigated. This method was highly specific and sensitive and stained both the encysted and the tachyzoite forms of the organism. Stronger contrast of the single parasite and better identification is possible if it is applied together with silver enhancement. Conventional staining and immunohistochemical peroxidase techniques are not advantageous, because they allow a diagnosis only by observation of the rare pseudocysts and not by free parasites in tissue, so the colloidal gold method appears to be the preferred method for a rapid diagnosis of cerebral toxoplasmosis, especially in cases where only small amounts of tissue can be obtained.

Acquired Immunodeficiency Syndrome↗

[Brain biopsies in HIV-infected patients].

Stereotactic brain biopsies of 25 HIV-seropositive patients (age range between 20 and 56 years, 23 males, 2 females) were retrospectively studied. Biopsy material was examined cytologically, histologically, immunohistochemically and electron microscopically. A definitive diagnosis could be established in 23 cases (92%). Diagnosis included non-Hodgkin's lymphoma (10 cases), toxoplasmosis (10 cases), progressive multifocal leukoencephalopathy (PML) (2 cases) and combined toxoplasmosis and lymphoma (1 case). Two biopsies were non-diagnostic. All lymphomas were B-cell lymphomas of high malignancy including one K1-lymphoma. In six cases, in which autopsy was performed, biopsy diagnosis could be confirmed. In one patient suffering from toxoplasmosis, autopsy demonstrated an additional cytomegalovirus infection. Conventional histology was not sufficiently decisive for toxoplasmosis, for some lymphomas and for PML. Stereotactic brain biopsy appears to be an effective method in the diagnosis of HIV-associated brain lesions.

Adult↗

Experience with the intraoperative frozen section technique for stereotaxic brain tumor biopsies.

The smear preparation technique is usually employed intraoperatively for stereotaxic brain tumor biopsies, whereas the frozen section technique is used in conventional operations, where larger tissue specimens can be obtained. 130 brain tumor biopsies were processed with the frozen section technique and postoperatively submitted to immunohistochemical examination. Subsequent paraffin embedding was not performed. In our study, frozen section diagnosis corresponded in 84% with the immunohistochemistry. Broggi et al. (1984) and Kleihues et al. (1984) demonstrated a similar positive correlation between intraoperative smear preparations and postoperative paraffin embedding. In our investigation, the greatest difficulties arose in cases of suspected lymphoma. Postoperatively, all lymphomas could be immunohistochemically clarified. Due to insufficient material 8% of the cases remained unclarified. Compared to smear preparation, the intraoperative frozen section technique during intervention provided a more accurate assessment of the histology. Furthermore the time needed for the procedure is not much longer than for smear preparation techniques. Reliable antibodies can be used in the remaining frozen material for further differentiation.

Biopsy↗

Microbial DNA topoisomerases and their inhibition by antibiotics.

Supercoiling of bacterial DNA is regulated by topoisomerases and influences most of the metabolic processes involving DNA. The present review is devoted to a brief outline of the supercoiled state of DNA in bacteria and to all microbial topoisomerases hitherto described. Recent studies on topoisomerases of archaebacteria led to the discovery of a so-called reverse gyrase, the properties of which are also discussed. Special emphasis is given to a selective treatment of the effects of those antibiotics which act as gyrase inhibitors.

Anti-Bacterial Agents↗

Variation of DNA sequence specificity of DNA-oligopeptide binding ligands related to netropsin: imidazole-containing lexitropsins.

CD binding studies of nonintercalative oligopeptides related to netropsin, named lexitropsins, have been carried out with synthetic duplex DNAs and natural DNA. While netropsin possesses a high dA.dT sequence specificity, these ligands show a progressive lowering of the ability to bind to dA.dT basepairs in DNA and a dramatic reduction of the sequence specificity seen at high salt concentration due to a replacement of pyrrole moieties by imidazoles. This variation in DNA sequence specificity of lexitropsins is mirrored in corresponding large differences in the template inactivation of poly(dA-dT).poly(dA-dT) in the RNA polymerase reaction by these drugs. The presence of imidazole permits binding of the oligopeptide to dG.dC pairs, which is most effective for the triimidazole peptide. Results at increasing salt concentration reveal, however, that a tight binding to pure dG.dC sequences does not occur. A proper sequence containing dG.dC and dA.dT pairs is supposed to be required for a higher specificity. The CD data accord well with previously reported melting studies and are in favor of recent theoretical results suggesting that the diminished AT preference may be due to an increase in the complexation energy with the dG.dC pairs.

Base Composition↗

Female labour force activity and the sex differential in mortality: comparisons across developed nations, 1950-1980.

This paper examines the macro-level relationship between female labor force activity and the sex differential in mortality among developed nations. Discrimination, protection, and null relationship hypotheses are tested using aggregate data for 18 high income nations over 7 time points from 1950 to 1980. High levels of female labor force activity--controlling for a variety of general social conditions--increase the longevity advantage women have over men. In some models the effects are immediate; in other models the effects occur after a substantial lag; but in no cases are there harmful effects for women's longevity. Also important for the differential are consumption of cigarettes and alcohol, and the level of income inequality in a society.

Alcohol Drinking↗

DNA binding protein from Streptomyces hygroscopicus: detection of binding by gel retardation, sedimentation and effects on the transcriptional activity in vitro.

The binding to supercoiled plasmid DNA as well as to double-stranded short DNA fragments of the DNA binding protein. ASBIII, from S. hygroscopicus has been demonstrated by gel retardation asay. As further revealed by sedimentation analysis, the protein-DNA complex formation also involves condensation of DNA and an aggregation step at higher total protein-to-DNA ratio (w/w). In vitro studies of the transcriptional activity of DNA-protein complexes showed that the ASBIII protein inhibits the overall template activity in the RNA polymerase II system to nearly similar extents for various DNA's. Preincubation of ASBIII-DNA complexes of different GC content, however, suggested a selective inhibitory effect on GC-rich DNA due to the higher stability of this complex. The results also indicate that the initiation of transcription of the GC-rich DNA template is affected by the ASBIII protein. The present results on the DNA binding properties and inactivation of the transcription of the ASBIII protein suggest that this protein may be a potential candidate for the local compaction of chromosomal DNA in Streptomyces hygroscopicus.

Animals↗

Binding of nonintercalative antitumor drugs to DNA-polymers: structural effects of bisquaternary ammonium heterocycles.

The binding of the antitumor agents SN-16814 nd SN-13232 to various DNA's in solution was monitored by CD and UV absorption measurements. In addition comparative studies with dA.dT containing duplex DNA of the related ligands SN-6136 and SN-6324 were included with respect to effects of structural variations. In general all four ligands show a dA.dT preference in their binding affinity to DNA. Differences were observed for the reaction of SN-16814 which contains bicyclic ring system: it has a lower base pair selectivity, shows some affinity to poly(dG-dC).poly(dG-dC), poly(rA).poly(rU) and poly(rU). The binding mechanism of SN-16814 is associated with a significant time dependent binding effect in CD spectra and UV absorption in case of reaction with poly(dA).poly(dT) and poly(dI).poly(dC) indicating a slow kinetics. The preferred binding to dA.dT base pairs in DNA decreases in the order from SN-61367 greater than SN-13232 greater than SN-6324,SN-16814 as judged from CD titration studies, salt dissociation and melting temperature data. Competitive binding experiments with netropsin (Nt) or distamycin-5 revealed that SN-16814 and SN-13232 are displaced from poly(dA.dT).poly(dA-dT) suggesting that both ligands are less strongly bound than Nt and Dst-5 within the minor groove of B-DNA. These studies are consistent with results of the DNAse I cleavage of poly(dA-dT).poly(dA-dT) which show the same relative order of inhibition of the cleavage reaction due to ligand binding. The results suggest that the variability of the DNA binding and dA.dT sequence specificity may reside in the adaptability of benzamide-type ligands in the helical groove which is influenced by distinct structural modifications of the ligand conformation.

Antineoplastic Agents↗

Interaction of the nonintercalative antitumour drugs SN-6999 and SN-18071 with DNA: influence of ligand structure on the binding specificity.

Binding to DNA's of the non-intercalative ligands SN-6999 and SN-18071 has been studied by means of circular dichroism, UV absorption, thermal melting and for SN-6999 by viscosity measurements. Both antitumour drugs show a preference for dA.dT rich DNA's, but the base pair selectivity of SN-18071 is lower as indicated by some affinity to dG.dC containing duplex DNA. The dA.dT base pair specificity of SN-6999 is comparable to that of netropsin. It forms very stable complexes with dA.dT containing duplex DNA and competes with netropsin binding on DNA. The ligands SN-18071 and pentamidine are totally released from their complexes with poly(dA-dT).poly(dA-dT) by competitive netropsin binding. The results demonstrate that hydrogen bonding capacity of the ligand in addition to other factors strongly contribute to the base sequence specificity in the recognition process of the ligand with DNA. A binding model of SN-6999 with five dA.dT pairs in the minor groove of B-DNA is suggested.

Antineoplastic Agents↗