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Biomedical subjects

C Zimmer

Publications and source records attributed to C Zimmer.

At least 109 records · Page 6Linked to original sources
PubMed1993

Studies on the ability of minor groove binders to induce supercoiling in DNA.

The effect of various non-intercalating minor groove binders on closed circular DNA in the presence of topoisomerase I has been studied by means of agarose gel electrophoresis. Analogues of the netropsin series (lexitropsins) and SN-6999 effectively produce positive supercoils, as indicated by analysis of the topoisomers in the presence of chloroquine and the evaluated linking number changes. Analogues of the distamycin series are less effective, and bisquaternary heterocycles, as well as DAPI and pentamidine, were found to be ineffective ligands. The large differences observed in the ability of minor groove binders to induce positive supercoils are discussed.

DNA Topoisomerases, Type I↗
PubMed1993

Binding to DNA of selected lexitropsins and effects on prokaryotic topoisomerase activity.

The binding behaviour toward DNA of some minor groove binders related to distamycin was studied by means of circular dichroism. In addition their influence on the activity of topoisomerases isolated from Streptomyces noursei has been investigated. The monocationic imidazole containing ligands (lexitropsins) show a decreased affinity to AT pairs but an increased affinity to GC pairs which contrasts the AT-preferred binding of Dst-2 and Dst-3. For the monocationic triimidazole containing lexitropsin the affinity for GC over AT pairs was most pronounced. It was also found that the imidazole containing lexitropsins are inhibitors of topoisomerases. These minor groove binders interfere more strongly with the DNA gyrase activity than with the prokaryotic topoisomerase I. Our results indicate that Dst-3 most effectively inhibits gyrase and topoisomerase I activity. However, the inhibitory effect is neither related to the base pair specificity nor to the binding strength of different ligands. The mechanism of interference of minor groove binders with topoisomerase activity is more complex. It is considered that different factors, such as the nature of the ligand together with their DNA binding parameters and the target sequences of the enzymes play a role in the inhibitory effects of minor groove binders.

Animals↗
PubMed1993

Minor-groove binders are inhibitors of the catalytic activity of DNA gyrases.

Non-intercalating DNA minor-groove binders may effectively inhibit the supercoiling activity of gyrases by influencing the enzyme recognition and cleavage site on DNA. For gyrase from Streptomyces noursei a wide range of inhibitory potency for different classes of ligands is observed. This can be explained by a number of structural and binding factors of the ligands competing with the gyrase on the target site of DNA, the mechanism of which is different from the classical gyrase inhibitors.

Animals↗
PubMed1993

Nerve reconstruction with glycerol-preserved allogenic grafts in the rat.

A variety of materials have been evaluated as potential nerve grafts. To date, none has been shown to be consistently equal with regard to functional outcome when compared to standard autogenous nerve grafts. In this study, nerves stored in glycerol were evaluated for their peripheral nerve regenerative capacity. Femoral nerves were harvested from Fischer rats and stored for a minimum of 100 days in 98% glycerol at 4 degrees C. They were grafted into femoral nerve gaps of Lewis rats. After 3 months, histologic, electrophysiologic, and morphometric (axon diameter) analyses revealed less regenerative response than nerve gaps grafted with fresh, syngeneic controls. The differences disappeared by 6 months, although neither graft technique achieved recovery comparable to unoperated nerves. Immunohistochemical evaluation demonstrated a modest immune response at 3 months, which subsided by 6 months. These findings are encouraging for the development of glycerol-preserved nerve graft banking.

Action Potentials↗
PubMed1993

Childhood asthma: mothers' affective attitude, mother-child interaction and children's compliance with medical requirements.

Maternal critical attitude (CA) and negative mother-child verbal interaction in families with an asthmatic child and in controls were investigated in the present study. Twenty-eight children with bronchial asthma (6-13 yr) and 23 healthy children with their mothers participated in the project. Mothers were asked to describe their child (Five Minute Speech Sample; FMSS). Mother and child were then asked to discuss a mutual problem (Problem Discussion; PD). Tape recordings were taken. The mothers' responses during the FMSS were used to assess CA. Negative verbal behavior during PD was coded by means of a reliable coding system for dyadic interaction. Significantly more mothers of the asthmatic children than of the controls showed CA during the FMSS. Mothers of the asthmatic children made significantly more critical remarks and offered more negative solutions during the PD. Within the asthma group mothers who made more critical remarks had to make more effort to have their child comply with the medical requirements. Additionally, mothers showing a higher total amount of negative verbal behavior had children with rather high IgE levels. There was no systematic difference between children having CA mothers with high vs low face-to-face contact.

Adaptation, Psychological↗
PubMed1993

Mechanisms of distamycin A/DAPI chromosome staining. I. Competition binding effects of nonintercalative DNA groove-binding agents in situ and in vitro.

The molecular mechanism underlying distamycin A-induced differential DAPI fluorescent staining of metaphase chromosomes was studied in Sus scrofa domestica both cytologically, using, besides DAPI, two isomeric derivatives of DAPI (D288.45 and D288.48), and molecularly, by in vitro competitive-binding studies using S. scrofa satellite DNA and synthetic DNA polymers. Significant differences in heterochromatin staining were observed between D288.45 and D288.48. Distinct distamycin A/DAPI bands were obtained with DAPI and D288.45 but not with D288.48. Circular dichroism measurements were performed to characterize the displacement of DAPI from its DNA binding sites by distamycin A and also netropsin. Distamycin A was most effective in displacing DAPI when DAPI was bound to contiguous clusters of AT base pairs and much less effective in displacing DAPI bound to GC or mixed AT/GC base-pair sequences. The results of these competitive-binding studies provide the basis of a molecular explanation of the quenching phenomenon of distamycin A counterstaining on chromosomal DAPI fluorescence.

Animals↗
PubMed1992

Age-related immunoreactivity pattern in medulloblastoma.

Thirty-five paraffin-embedded medulloblastomas (19 from children and 16 from adults; 24 classic medulloblastomas, 10 desmoplastic medulloblastomas, 1 tumor with neuronal differentiation) were examined for reactions with antibodies against glial fibrillary acidic protein (GFAP), cytokeratins KL1 and MNF116, desmin, and vimentin. Only the tumor from the youngest patient, a 152-day-old boy, showed a positive immunoreaction for cytokeratins. Because of this age-related expression of cytokeratins in medulloblastomas primarily in very young children, cytokeratin positivity was interpreted as a sign of tumor immaturity. Five medulloblastomas showed scattered GFAP-positive reactive astrocytes and/or other positive, probably neoplastic, cells. Only two tumors showed GFAP immunoreactivity in unequivocally neoplastic cells. Of six tumors that reacted with vimentin, three showed strong reactivity throughout, one being the tumor from the 152-day-old boy. The remaining three demonstrated nests of vimentin-positive cells with weak or intense somatic immunoreactivity for vimentin. None of the 35 cases showed positivity for desmin; indicating that mesenchymal differentiation is restricted to the rare so-called medullomyoblastomas.

Adolescent↗
PubMed1992

Stereotactic brain biopsy in AIDS.

In the hope of finding a treatable condition, the need for rapid diagnosis in HIV-seropositive patients with brain lesions is apparent. In order to evaluate the efficacy of stereotactic brain biopsy in AIDS patients, we retrospectively studied 25 HIV-infected patients undergoing stereotactic biopsy. Brain lesions were identified with gadolinium-enhanced MRI and/or contrast CT. Brain biopsy was performed using the system of Riechert. From 8 up to 15 small tissue samples from one or two targets were obtained in every patient. The biopsy material was examined cytologically, histologically (including electron microscopy), immunohistochemically and, in part, by animal test and polymerase chain reaction (PCR). A definite diagnosis was achieved in 92%. Diagnosis included primary central nervous system lymphoma (PCNSL) (10), toxoplasmosis (10), progressive multifocal leukoencephalopathy (2) and one case of co-existing toxoplasmosis and cytomegalovirus infection. Two biopsies were non-diagnostic. All PCNSLs showed polymorphic B-cell populations of high malignancy; accurate classification according to the Kiel classification was not possible. In 3 lymphomas Epstein-Barr nuclear antigen (EBNA) 2-mRNA could be detected by PCR and confirmed immunohistochemically by EBNA 2 expression. In 6 cases autopsy confirmed the biopsy diagnosis. Conventional histology was not sufficiently decisive for toxoplasmosis and progressive multifocal leukoencephalopathy, so that immunohistochemistry and animal tests became very important for a final diagnosis. With the help of different morphological and molecular biological techniques stereotactic brain biopsy appears to be an effective method in the diagnosis of HIV-associated brain lesions. In view of the marked radio- and chemosensitivity of PCNSLs it is mandatory to establish an early and accurate histological diagnosis for adequate treatment.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Melanoma-associated antigens in tumours of the nervous system: an immunohistochemical study with the monoclonal antibody HMB-45.

The aim of this study was to determine the specificity and sensitivity of the commercially available, monoclonal anti-melanoma antibody HMB-45 in brain tumours and peripheral nerve sheath tumours. Hence, a series of 155 different non-melanotic tumours of the central and peripheral nervous system were examined immunohistochemically. The brain lesions consisted of primary tumours and metastases from various carcinomas. Twenty melanotic tumours (cerebral metastases of malignant melanomas, meningeal melanomatosis, meningeal melanocytomas) and dermal blue cell naevi served as controls. All melanotic tumours stained positive. Furthermore, a positive immunohistochemical reaction was observed in the following non-melanotic tumours: gliosarcomas, primitive neuroectodermal tumours, ependymoma, malignant schwannomas and different intracranial hamartomas. Two plasmacytomas and 4 metastatic carcinomas also revealed positive staining for HMB-45. Our results confirm the necessity for cautious interpretation of HMB-45 immunoreactivity as a tool in the immunohistochemical characterization of nervous system tumours.

Antibodies, Monoclonal↗
PubMed1992

Childhood asthma: paternal critical attitude and father-child interaction.

The study investigated paternal critical attitude (CA) and negative father-child communication in families with an asthmatic child and in controls. Twenty-seven children with bronchial asthma (6-13 yr) and 23 healthy children with their fathers participated in the project. Fathers were asked to describe their child (Five Minute Speech Sample; FMSS). Additionally, father and child discussed a mutual problem (Problem Discussion; PD). Tape recordings were taken. Critical attitude (CA) was assessed from the fathers' responses during the FMSS. Negative verbal behavior during PD was coded for father and child. During the FMSS, significantly more fathers of the asthmatic children than of the controls showed CA. During the PD, fathers of the asthmatic children made significantly more critical remarks than their controls. Significantly more long sequences of negative verbal communication occurred in father-child dyads with an asthmatic child than in the control dyads. No significant relationship was found between either the fathers' attitudes or amount of negative verbal communication and the children's severity of asthma, compliance, or IgE status.

Adolescent↗
PubMed1992

Acute systemic heat stress increases glial fibrillary acidic protein immunoreactivity in brain: experimental observations in conscious normotensive young rats.

The possibility that astrocytes participate in the pathophysiology of thermal brain injury caused by systemic heat exposure was examined in conscious young rats. The temporal and regional pattern of the astrocytic response to thermal injury was characterized by demonstrating the immunoreactivity of glial fibrillary acidic protein (GFAP) using monoclonal antibody and avidin-biotin complex technique. Exposure of conscious young animals to heat at 38 degrees C for 4 h in a biological oxygen demand incubator resulted in a marked increase of the GFAP immunoreactivity in specific brain regions as compared with the intact controls. The intensity of the increased GFAP immunoreactivity was mainly noted in pons, medulla and cerebellum, followed by thalamus, hypothalamus, hippocampus and caudate nucleus. The cerebral cortex of heat-exposed animals showed only a mild increase in GFAP immunoreactivity which was predominantly concentrated in cingulate, parietal and pyriform cortices. The immunostaining in general was seen in the perivascular glia, within the neuropil and the glia limitans. This increase in GFAP immunoreactivity was absent in animals exposed to the same ambient temperature (38 degrees C) for 1 h and 2 h, or at a lower temperature (36 degrees C) for 4 h. These results show that (i) astrocytes actively participate in the pathophysiology of heat stress, (ii) endogenous thermal brain injury elicits activation and hypertrophy of astrocytes ("reactive gliosis") depending on the magnitude and duration of the ambient heat stimulus, and (iii) the astrocytic reaction (observed as increased GFAP immunostaining) could be induced much more rapidly within a very short survival period of 4 h, not reported earlier.

Animals↗
PubMed1992

Proliferating cell nuclear antigen (PCNA) in atypical and malignant meningiomas.

Because it is not easy to determine the tumor status of meningiomas by current diagnostic procedures, we investigated these tumors immunohistochemically using the monoclonal antibody PC 10. This antibody recognizes a fixation- and processing-resistant epitope of the proliferating cell nuclear antigen (PCNA), which is a 36-KD nuclear antigen associated with the cell cycle. We studied paraffin-embedded and formalin-fixed tissue specimens of a group of 21 atypical/malignant meningiomas together with 18 benign meningiomas. PCNA staining results were compared with the mean number of silver-stained nucleolar organizer region-associated proteins (AgNORs), tumor grading, and mitotic indices of these tumors. The percentage of PCNA-positive cells was found to range between 0.1% and 40%, irrespective of the tumor grade. When all tumors were collectively considered, no positive correlation was found between PCNA scores and histologic grading and only a weak one between PCNA score and mitotic index. A higher correlation was seen between AgNOR counts and tumor grading. Our results suggest that PCNA labeling and histologic grading seem to be independent parameters. The correlations found between AgNOR counts and tumor grading should be substantiated in further series.

Antigens, Nuclear↗
PubMed1992

Neuropathy with lysosomal changes in Marinesco-Sjögren syndrome: fine structural findings in skeletal muscle and conjunctiva.

The light- and electron-microscopical findings in the skeletal muscle and conjunctiva of 6 patients with Marinesco-Sjögren syndrome (MSS) were presented. All patients were related and showed the cardinal clinical symptoms of the syndrome: congenital cataracts, mental retardation, delayed statomotor development, and cerebellar ataxia. The most prominent alteration found in the skeletal muscle of four patients was extensive neurogenic atrophy with conspicuous groups of atrophic muscle fibers. Additional findings were vacuolar degeneration and secondary, unspecific changes like slight mitochondrial alterations and increased variability in muscle fiber calibers. The ultrastructural examination revealed double-membrane structures near to, but not in direct contact with the nucleus. The nuclear changes described earlier (7, 20) were not found in any of the cases. Conjunctival biopsies revealed a marked increase in the number of lysosomes in fibroblasts. In summary, to the well known myopathic damage of muscles in MSS a neurogenic component should be added. Disturbed lysosomal function is to be considered as the basic abnormality, though the enzyme defect has not yet been identified. In cases of clinically suspected MSS, examination of a conjunctival biopsy is highly recommended.

Conjunctiva↗
PubMed1992

DNA binding of the nonintercalative ligands SN-6132, SN-6131 and SN-6113: minor variations of the ligand structure may cause changes in the base pair preference.

The DNA binding selectivity of three ligands of a series of antitumor agents of bisquaternary ammonium heterocycles has been investigated by means of CD spectroscopy and melting measurements. From the spectroscopic results and binding data it is concluded that the agents SN-6132, SN-6131 and SN-6113 have relatively high affinity to AT base pair sequences whereas the binding to GC pairs is very low. The binding selectivity to AT base pair sequences decreases in the order netropsin > SN-6132 > SN-6113 > SN-6131. Poly(dA).poly(dT) has the highest binding preference for SN-6132 relative to that of SN-6131. The different binding behavior of the ligands is related to their distinct changes in the chemical structure and to the DNA minor groove properties which determines the adaptability of the ligands in the groove.

Antineoplastic Agents↗
PubMed1992

Influence of preoperative dexamethasone therapy on proliferating cell nuclear antigen (PCNA) expression in comparison to other parameters in meningiomas.

We conducted a trial in 42 benign and malignant meningiomas to assess a possible influence of preoperative dexamethasone therapy on mitotic index, labelling indices of proliferating cell nuclear antigen (PCNA), progesterone receptor, epidermal growth factor receptor (EGF-R), c-erbB-2 oncoprotein, cathepsin D, gamma-gamma enolase as well as the mean number of silver-stained nucleolar organizer region-associated proteins (AgNORs). Tumors with preceding dexamethasone therapy for more than 1 day display significantly less immunohistochemical staining for PCNA. A correlation between the labelling index of PCNA and the degree of malignancy could not be identified. There was no significant effect of preoperative dexamethasone therapy on the other parameters. Our data suggest that dexamethasone may selectively inhibit the expression of PCNA in the G1/S-phase of the cell cycle. Thus, we emphasize the necessity to heed factors, e.g. dexamethasone, which may affect the expression of proliferating markers.

Adult↗
PubMed1992

[Changes of microenvironment and tumor cell heterogeneity--consequences for bioptic diagnosis].

During the last several decades, immunohistochemical studies of tumors, along with other approaches, have suggested that the clinical and biological progression results, at least in part, from the sequential appearance within the neoplasm of cellular subpopulations whose new characteristics reflect specific somatic genetic changes. However, CNS may provide a different microenvironment for activation and proliferation than other tissues. The tissue-specific distribution of intermediate filament proteins, in particular the keratins, permits their use as marker in histopathology, but several important exceptions are recognized. In this connection, it is of interest that, according to the other reports, glial tumors may be positive for different anti-keratin antibodies. However, the gliomas did not show an immunoreaction in any of the cases when HEA-125 and Ber-EP4 were applied. The great number of multihormonal pituitary adenomas and possible change of the immunohistochemically detectable hormone status in cases of recurrent tumors have particularly re-emphasized the need for new thinking about patterns of classification. The diagnosis of malignant melanoma has been considerably facilitated recently by the introduction of immunohistological labelling with antibodies selective against melanoma antigen (HMB-45). Our results confirmed the necessity of cautious interpretation of HMB-45 immunoreactivity because a HMB-45 expression can be observed in several non-melanotic tumors.

Adenoma↗
PubMed1991

Immunohistochemistry of primitive neuroectodermal tumors in infants with special emphasis on cytokeratin expression.

Eleven primitive neuroectodermal tumor (PNET) biopsies from infants under the age of 3 years were studied for the presence of various differentiation markers for neuroectodermal stem cells. Special emphasis was placed on the expression of cytokeratin proteins. The tumor cells expressed different cytokeratin proteins (CK8, CK13, CK18, CK19, KL1, AE1/AE3, MNF16) in 3 of 11 cases. These cases were furthermore characterized by a strong expression of glial fibrillary acidic protein, S-100 protein and vimentin. Vimentin and cytokeratin proteins were co-expressed; cross-reactivity between these two intermediate filaments could be excluded by immunoblotting. It is noteworthy that the three positive tumors were all from infants in their 1st year. We assume that PNETs in early infancy are characterized by a particularly wide range of differentiation patterns. The presence of cytokeratin proteins in these cases seems to be associated with the expression of vimentin and must be regarded as an indicator of an early developmental stage of the tumor cells.

Child, Preschool↗