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Biomedical subjects

L Anker

Publications and source records attributed to L Anker.

8 recordsLinked to original sources
PubMed1996

Enhancement of radiosensitivity in human malignant glioma cells by hypericin in vitro.

Hypericin, an antidepressant and antiviral agent being evaluated in phase I and II trials for patients with HIV infection, is known to be a potent protein kinase C inhibitor. We have investigated its effects on cellular response to radiation via a tetrazolium-formazan cell growth rate assay using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide and clonogenic assay in three human glioblastoma cell lines, U87-MG, A-172, and T98G, and a low-passage malignant glioma culture, 93-492. At a concentration of 5 microM, hypericin inhibited these cells slightly but caused significant radiosensitization (e.g., the cell survival rate after the radiation treatment was 50.2 and 26.0% in cells treated with 6 Gy and 6 Gy plus 5 microM hypericin in U87-MG cells, respectively; P = 0.0285). Hypericin also enhanced the radiosensitivity significantly in the low-passage glioma 93-492 cells. These findings suggest that hypericin represents a potential new agent in combination with radiation therapy of malignant gliomas.

Anthracenes↗
PubMed1994

Lovastatin induces growth inhibition and apoptosis in human malignant glioma cells.

The competitive HMG-CoA reductase inhibitor lovastatin has been shown to suppress growth and induce morphological changes in a variety of non-glioma tumor cell lines. This study assesses the effects of this agent on the growth and survival of the human malignant glioma cell lines A172 and U87-MG. The response to the drug was investigated using a cell proliferation assay which revealed significant dose-dependent growth inhibition. Treatment with as little as 100 nM lovastatin over a period of 72 hours led to DNA degradation into nucleosome-sized fragments characteristic of apoptosis. Our data suggest that HMG-CoA reductase inhibitors such as lovastatin merit further investigation as potential therapeutic agents for the treatment of malignant gliomas.

Apoptosis↗
PubMed1993

p53 protein accumulation and gene mutations in human glioma cell lines.

Mutations in, and aberrant expression of, the p53 tumor suppressor gene were assessed in 17 cell lines derived from human malignant brain tumors (glioblastoma multiforme). Exons 5 through 8 were screened by single strand conformational polymorphism analysis (SSCP), followed by direct DNA sequencing. Mutations were found in 6 of 17 glioma cell lines, i.e., at a frequency similar to that found in primary malignant gliomas. Loss of the wild type allele was observed in 4 of the mutated cell lines. Two cell lines had the same mutation (CGG-->TGG; Arg-->Trp) in codon 248. Five of 6 mutations were transitions, 4 of which occurred at CpG dinucleotides. In one cell line a 10-bp deletion at the intron 4/exon 5 junction was found. Five of 6 glioma cell lines contained a mutation identical to that in the respective primary tumor despite prolonged in vitro culture (140-221 passages). Thus, the acquisition of p53 mutations during culture appears to be infrequent. Two cell lines derived from heterozygous tumors maintained the wild type p53 allele during long term culture. p53 protein levels were assessed by immunofluorescence cytochemistry and immunoprecipitation followed by Western blot analysis and revealed elevated levels of the p53 protein, although to a variable extent, in all cell lines with p53 mutations. A marked p53 protein accumulation was also observed in two cell lines lacking p53 mutations in exons 5 through 8, indicating that a prolonged half life of the gene product is not solely dependent on an aberrant coding sequence. The remaining cell lines had either low levels or no detectable p53 protein; one of the latter contained a gross rearrangement of the p53 gene. Our results suggest that with respect to p53 gene status, glioma cell lines usually resemble the original tumors and may, therefore, be suitable for studying the biological changes associated with p53 mutations in glial tumors.

Base Sequence↗
PubMed1992

Filling the gaps. Systems offer two models of care management: community outreach and inpatient care.

The growing number of vulnerable people, such as the elderly and people with long-term disabilities, calls for healthcare providers to offer more programs to ensure a continuum of care. Client-focused care management programs offer access to such a continuum. Care managers understand services and reimbursement and can pull it all together for the client. The Sisters of Charity Health Care Systems, Cincinnati, have two models of care management. St. Joseph Coordinated Care provides extensive outreach to a large, culturally diverse New Mexico community, serving urban and rural clients. Penrose-St. Francis Healthcare System offers inpatient medical care management in Colorado. Coordinated Care at St. Joseph Healthcare System in Albuquerque is comprehensive, covering a wide spectrum of client needs--medical, social, and psychological. The program's central goal is to help individuals remain safely at home. Persistence and devotion to the client are the hallmarks of effective care management and the foundation of the new geriatric care management program at Penrose-St. Francis Healthcare System in Colorado Springs, CO. The program's goals are to improve inpatient geriatric care, smooth the patient's transition to alternative care settings, and ensure efficient and effective resource use during the patient's hospital stay.

Aged↗
PubMed1981

A theoretical conformational study of substituted O-anisamides as models of a class of dopamine antagonists.

The quantum mechanical PCILO method has been used to investigate the conformational behaviour of N-(2-aminoethyl)- and N-(2-dimethylaminoethyl)-o-anisamide, two model molecules of substituted benzamides. The molecules are shown to have only limited conformational freedom due to the presence of two intramolecular hydrogen bonds acting as conformational locks. The molecules in their preferred conformation are characterized by a distance between the centre of the aromatic ring and the nitrogen atom of almost 6 A, i.e. almost 1 A longer than in the fully extended dopamine conformers. Some implications at the receptor level of this topographical dissimilarity are discussed.

Benzamides↗
PubMed1975

[General methods and specifications].

The reasons are explained why general methods are described in pharmacopeias. With the help of examples taken from European Pharmacopeias, the United States Pharmacopeia, and the International Pharmacopeia, the author reports the general chemical and physical methods that were used in compiling these pharmacopeias. The description of these general methods, and particularly of the instruments, goes often beyond the actual bounds of a pharmacopeia and may fulfill a didactic function. The methods used in the various pharmacopeias, especially the chemical ones, are here compared and subjected to the author's critical analysis. The author explains also that technical progress in the analytical field should not be hampered by the rigidity of the pharmacopeia's rules; this can be easily avoided by resorting to alternate methods.

Chemistry, Pharmaceutical↗
PubMedDate not supplied

Systematic determination of telomerase activity and telomerase length during the progression of human breast cancer in cell culture models.

The purpose of the study was to determine systematically the expression of telomerase activity and the length of telomere repeat arrays by utilizing two different cell culture models that derive from normal individual donors, and probably represent various stages of human breast oncogenesis in cell culture. The models consist of mortal, non-tumorigenic immortal and tumorigenic immortal human mammary epithelial cell (MEC) lines. Using a recently developed polymerase chain reaction (PCR)-based telomeric repeat amplification protocol (TRAP) assay, telomerase activity was undetectable in mortal MEC cells. In contrast, the immortal MEC that were nontumorigenic or tumorigenic in immunosuppressed athymic mice, showed telomerase activity. The absence of telomerase activity in mortal and its presence in both non-tumorigenic and tumorigenic immortal cell lines did not reflect their proliferative rate, as demonstrated by the similar pattern and intensity of reactivity of these cell lines with anti-Ki 67 antibody which recognizes a human nuclear cell proliferation--associated antigen. Southern blot analyses of Hinf I-digested genomic DNA hybridized with a (TTAGGG)4 probe revealed arrays of telomeric repeat lengths ranging from 3 to 5, 3.5 to 9, 3.2 to 9 or 3 to 15 kilobase pair (kbp) for mortal, nontumorigenic immortal, and tumorigenic immortal or established MEC lines respectively. These results suggest that telomerase activity and stable telomeric repeat lengths may be a molecular phenotype of the early stages in the progression of breast cancer.

Animals↗