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Biomedical subjects

M Weller

Publications and source records attributed to M Weller.

389 records · Page 22Linked to original sources
PubMedDate not supplied

Fish trypanosomes: their position in kinetoplastid phylogeny and variability as determined from 12S rRNA kinetoplast sequences.

Fish trypanosomes have traditionally been classified according to the host species from which they were isolated, each isolate being regarded as a distinct species. To test the soundness of this practice, the genetic variabilities of the kinetoplast 12S rRNA-encoding genes of different fish trypanosomes isolates were compared. The DNAs were extracted from trypanosomes cloned from blood samples of 15 donors representing ten different fish species in four orders from waters of three major river systems of Central and Northern Europe. Comparison with other trypanosomatid sequences revealed that the fish trypanosomes form a monophyletic group with Trypanosoma brucei as a sister group. Pairwise comparisons of genetic distances yielded a wide range of continuous variation with no indication of any discontinuities attributable to barriers to gene flow. The genetic distances did not correlate with either the identity of the host species or geography. The host specificity of fish trypanosomes appears to be limited.

Animals↗
PubMedDate not supplied

Mononuclear phagocytes in proliferative vitreoretinopathy (PVR). A specific role of microglial cells in non-traumatic disease?

Mononuclear phagocytes have been a focus of attention in the cellular biology of proliferative vitreoretinopathy (PVR) for more than ten years. The pattern of phagocyte participation in periretinal traction membrane formation in PVR depends on the etiology, i.e. trauma, rhegmatogenous retinal detachment, previous therapy, i.e. multiple surgical interventions, and the clinical stage of the disease. We have recently identified microglial cells as a distinct cellular population, in membranes from patients with non-traumatic PVR. Current evidence of mononuclear phagocyte function in PVR suggests a role for resident phagocytes of the vitreous and retina in PVR subsequent to rhegmatogenous detachment, and a role for blood-derived monocytes in post-traumatic PVR. The cellular biology of PVR may be much more heterogeneous than previously assumed.

Diabetic Retinopathy↗
PubMedDate not supplied

Thrombospondin: a new attachment protein in preretinal traction membranes.

Thrombospondin (TSP), an adhesive integrin-binding protein of plasma and platelets, was detected in preretinal traction membranes from patients with idiopathic (8/8) and traumatic (7/8) proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR) (6/8). TSP immunoreactivity was compared to the pattern of von Willebrand factor, plasma transglutaminase (blood coagulation factor XIII), fibronectin, and mononuclear phagocytes, using double-label immunofluorescence microscopy. TSP was partially colocalised with the endothelial cell marker, von Willebrand factor, in PDR. The codistribution of catalytic factor XIII and two cross-linking substrates, fibronectin and TSP, suggests a functional role of the enzyme in the extracellular matrix build-up in PVR and PDR. No significant TSP synthesis by mononuclear phagocytes was observed. Western blotting indicated a plasmin-mediated intravitreal breakdown of presumably plasmatic TSP in PVR and PDR.

Antibodies, Monoclonal↗
PubMedDate not supplied

Topotecan-based combination chemotherapy for human malignant glioma.

BACKGROUND: Topotecan has been considered a promising agent for the adjuvant chemotherapy of human malignant glioma because of its novel mode of action, its activity against other solid tumors, and its good penetration across the blood-brain barrier. However, the clinical effects of topotecan monotherapy in malignant glioma have been disappointing. MATERIALS AND METHODS: We sought to identify suitable partners for topotecan combination chemotherapy of malignant glioma using two well-characterized human malignant glioma cell lines, T98G and LN-229. The effects of co-exposure to topotecan and other chemotherapy drugs were assessed in cytotoxic and clonogenic cell death assays. RESULTS: We found additive, less-than-additive, or occasional antagonistic effects, but never synergistic activity of topotecan with either CCNU, VM26 or vincristine, in acute cytotoxicity or in clonogenic cell death assays, with simultaneous or sequential drug exposure. VM26 or vincristine followed by topotecan yielded the most favourable results. Further, prolonged exposure of the glioma cells to topotecan and either CCNU, VM26, vincristine, cisplatin, doxorubicin or cytarabine resulted in additive but not synergistic growth inhibition. CONCLUSIONS: The present study fails to identify a specific partner for topotecan-based combination chemotherapy of malignant glioma among the chemotherapeutic drugs examined here. While this does not exclude a possible synergy of the drug combinations examined here in vivo, a focus on novel partners for topotecan or topotecan-based chemoimmunotherapy may be more promising.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Irradiation induced clonogenic cell death of human malignant glioma cells does not require CD95/CD95L interactions.

BACKGROUND: Radiotherapy is the single most effective therapy for malignant gliomas. Targeting the CD95 apoptotic pathway is a promising experimental approach to these neoplasms. Here, we asked whether irradiation modulates CD95-mediated apoptosis of human malignant glioma cells in vitro. MATERIALS AND METHODS: LN-18, LN-229 and T98G human malignant glioma cell lines were irradiated with dosages from 0-8 Gy and treated with CD95L (CD95 ligand). CD95 expression was assessed by flow cytometry. Caspase activity was determined by DEVD cleavage. Cytotoxic effects were assessed by crystal violet staining of cells in a 96-well plate assay. Clonogenic cell death was determined by a standard colony forming assay. RESULTS: We find that (i) CD95L-induced apoptosis, but not irradiation-induced clonogenic cell death, involves caspase 3 activation and is blocked by the viral caspase inhibitor, crm-A. (ii) Irradiation does not modulate CD95 expression either in p53 wild-type or in p53 mutant glioma cell lines, and does not enhance CD95L-evoked caspase 3 activity or CD95L-induced clonogenic cell death. CONCLUSIONS: We conclude that endogenous CD95/CD95L interactions are not involved in radiation-induced clonogenic cell death and that the killing cascades of CD95L and irradiation are independent in human malignant glioma cells.

Apoptosis↗
PubMedDate not supplied

Hyperthermia enhanced chemosensitivity of human malignant glioma cells.

In an effort to overcome chemoresistance of human malignant glioma cells, the modulation of drug-induced cell death by hyperthermia was assessed in 4 human malignant glioma cells lines, LN-18, LN-229, T98G and U87MG. Compared to normothermic conditions, pulsed 24 h drug exposure enhanced the sensitivity of glioma cells most strikingly with teniposide, treosulfan, topotecan and cisplatin, moderately with vincristine, CCNU and doxorubicin, but not with gemcitabine. Susceptibility to hyperthermia-mediated drug sensitization, varied significantly with T98G and LN-229 being strongly sensitized and U87MG being most resistant to the effects of hyperthermia. Hyperthermia did not significantly modulate drug-induced changes in cell cycle distribution. The degree of sensitization was independent of p53 status and of multidrug resistance (mdr) activity. Hyperthermia may thus be a useful approach to overcome, chemoresistance of human malignant glioma cells.

Antineoplastic Agents↗
PubMedDate not supplied

Heat shock protein expression in human gliomas.

BACKGROUND: Heat shock proteins (HSP) are cytoprotective, antiapoptotic proteins which may predict clinical prognosis in various types of cancer. Here, we asked whether the differential response to radiochemotherapy and different overall prognosis for astrocytic and oligodendroglial tumours can be accounted for by differences in HSP expression. MATERIAL AND METHODS: We examined aB-crystallin, HSP27, HSP70, HSC70 (HSP73) and HSP90 expression in 44 human gliomas (5 anaplastic and 5 low-grade astrocytomas, 5 anaplastic and 5 low-grade oligodendrogliomas and 24 glioblastomas) by immunohistochemistry. RESULTS: HSP were expressed in the tumour parenchyma of all high-grade and most low-grade gliomas, including oligodendrogliomas. Endothelial cells were more often positive for HSC70 and HSP90, but more often negative for HSP27, in glioblastomas than in the other tumours. HSP were also observed in macrophages/microglial cells, but not in a tumour-specific pattern. CONCLUSION: Different patterns of HSP expression seem not to account for the differential response of these tumours to adjuvant cytotoxic therapy.

Astrocytoma↗
PubMedDate not supplied

Identification by suppression subtractive hybridization of p21 as a radio-inducible gene in human glioma cells.

BACKGROUND: Radio-gene therapy involves the delivery, to tumor cells, of a therapeutic transgene whose expression is controlled by irradiation. MATERIALS AND METHODS: Here, we sought to identify novel radio-inducible transcripts in U87MG human malignant glioma cells using suppression subtractive hybridization (SSH). RESULTS: Of 998 clones from a subtracted library of irradiated U87MG cells, 24 candidate clones were identified by dot blot and 3 clones were confirmed as having been induced by irradiation by Northern blot analysis. All three clones showed 99-100% homology to the cyclin-dependent kinase (cdk) inhibitor, p21(Waf/Cip1). A screening of 12 human malignant glioma cell lines revealed that irradiation increased p21 mRNA expression and p21 protein levels levels in all of the five cell lines retaining p53 wild-type activity in a p53 reporter assay, but in none of seven p53 reporter-negative cell lines. CONCLUSION: Irradiation induces p21 mRNA expression in a strictly p53-dependent manner and may only enhance the expression of a limited number of genes in glioma cells. We conclude that the identification of radio-inducible genomic sequences suitable for radio-gene therapy may turn out to be difficult.

Cyclin-Dependent Kinase Inhibitor p21↗
PubMedDate not supplied

[Prevention of secondary cataract by intracapsular administration of the antimitotic daunomycin].

Pharmacological inhibition of capsule opacification e.g. using antimitotics such as daunomycin is a promising concept. Our own in vitro studies on cultured porcine lens epithelial cells have shown, that daunomycin penetrates the cells within at least 5 minutes. It possesses a low acute cytotoxicity and significantly inhibits epithelial cell proliferation at dose dependent concentrations ranging from 2.5 to 7.5 mg/l. In addition, in vitro studies on isolated pig corneas showed almost no corneal endothelial toxicity. After 10 resp. 30 min. exposure to 7.5 mg/l daunomycin, there was only 4.8 +/- 1.6 resp. 6.1 +/- 1.5% endothelial damage that dit not significantly differ from BSS serving as control. Encouraged by our clinical experience of good anterior segment tolerance of 7.5 mg/l daunomycin when used during vitrectomy in PVR, we started a prospective clinical trial to assess the effect to daunomycin on capsular opacification after ECCE with endo-capsular IOL implantation using the envelope technique. After agreement of the medical ethic commission we chose 6 patients with a mean age of 78 (72-83), no other ocular or general diseases and bilateral cataract of identical morphology and density. After written consent of the patients their first eye was operated using BSS as control. At least 4 weeks later the second eye was operated and received 0.5 ml of daunomycin (7.5 mg/l) applied during 5 minutes into the cleaned capsular bag, leaving the anterior capsular flap and a Healon filled anterior chamber to protect the surrounding intraocular structures. Mean postoperative control time actually is 12 (6-17) months for the controls and 10 (5-14) months for the eyes treated with daunomycin.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMedDate not supplied

Antioxidants specifically inhibit cisplatin cytotoxicity of human malignant glioma cells.

BACKGROUND: Human malignant gliomas are resistant to chemotherapy. Here, we examine the modulation of drug-induced cytotoxicity and clonogenic cell death of glioma cells by antioxidants. MATERIALS AND METHODS: We studied the effects on drug toxicity of three structurally unrelated antioxidants, N-acetylcysteine, superoxide dismutase or phenyl-N-tert-butyl-alpha-phenylnitrone, in acute cytotoxicity and clonogenic cell death assays in LN-18, LN-229 and T98G cells. Two fluorescent dyes, 2',7'-dichlorodihydroJluorescein diacetate (DCF-Hr2) and dihydro-rhodamine-123, were used to monitor free radical formation after drug exposure. RESULTS: The antioxidants inhibited acute cytotoxicity and clonogenic cell death induced by cisplatin in all cell lines but had little effect on the toxicity of BCNU, doxorubicin, VM26, vincristine, cytarabine or camptothecin. Cisplatin toxicity was not associated with free radical formation and was not potentiated by L-buthionine-[S,R]-sulfoximine-induced glutathione depletion. CONCLUSION: Antioxidants specifically inhibit cisplatin cytotoxicity of human malignant glioma cells in the absence of drug-induced free radical formation.

Acetylcysteine↗