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Biomedical subjects

G Roos

Publications and source records attributed to G Roos.

At least 37 records · Page 2Linked to original sources
PubMed2001

[Sudden cardiac death from unrecognized cardiac sarcoidosis].

Sarcoidosis is a systemic disease of young adults. Cardiac involvement is rarely diagnosed clinically. It presents with arrhythmias, conduction disorders, increasing myocardial insufficiency, or sudden death. We report a 42-year-old man with cardiac conduction disturbances of unknown cause who died of sudden cardiac death. Sarcoidosis with prominent cardiac involvement was diagnosed only at autopsy. Cardiac sarcoidosis should be considered in young patients with unexplained conduction disorders.

Adult↗
PubMed2001

Detailed clonality analysis of relapsing precursor B acute lymphoblastic leukemia: implications for minimal residual disease detection.

Genetic instability has important implications for detection of minimal residual disease (MRD) when the target is a clonal genetic marker revealed at diagnosis. A successful MRD detection approach requires a stable marker and for lymphoid leukemias clonal rearrangements of immunoglobulin (Ig) and T cell receptor (TCR) genes are commonly used. In the present study, Ig heavy chain (IgH) and TCR (gamma and delta) genes were studied in 18 consecutive, relapsing precursor-B ALL patients. At least one clonal rearrangement was found in all cases at presentation (IgH 94%, TCRgamma 39% and TCRdelta 28%). An altered rearrangement pattern between diagnosis and relapse was demonstrated in 14 patients (78%). At least one stable molecular target was found in 13 out of 18 cases (72%). Clonal differences between diagnostic and relapse samples were explained by: (1) loss of original rearrangements; (2) V(H) to DJ(H) joining; (3) V(H) gene replacement; (4) appearance of new rearrangements. In two cases with apparently new IgH gene rearrangements at relapse extended sequencing of the diagnostic samples revealed minor clonal rearrangements identical to the relapse clones. Interestingly, one patient displayed instability on both the IgH and TCR gene loci, whereas a stable Igkappa rearrangement was found at presentation and relapse. These data show that clonal diversity is common in precursor-B ALL and strongly suggest that MRD detection should include multiple gene targets to minimize false-negative samples. Even so, five of our 18 relapse cases (28%) lacked stable clonal markers and should have been unsuitable for MRD detection.

Adult↗
PubMed2001

Isoterchebulin and 4,6-O-isoterchebuloyl-D-glucose, novel hydrolyzable tannins from Terminalia macroptera.

Two new hydrolyzable tannins, isoterchebulin (1) and 4,6-O-isoterchebuloyl-D-glucose (2), together with six known tannins, 3-8, were isolated from the bark of Terminalia macroptera. Their structures were elucidated by extensive 1D and 2D NMR studies, MS, and chemical transformations. Biological activities of all compounds were evaluated against the snail Biomphalaria glabrata, the bacteria Bacillus subtilis and Pseudomonas fluorescens, the nematode Caenorhabditis elegans, and four cancer cell lines (Hep G2, MCF-7/S, MDA-MB-231, and 5637 cells). All compounds except 3 showed antimicrobial activities against B. subtilis (MIC 8-64 microg/mL), whereas only 1 was active against C. elegans (100 microg/mL) and B. glabrata(LC(100) = 60 microg/mL). 3 and 8 were toxic against 5637 cells with LC(50) = 84.66 and 41.40 microM, respectively.

Africa↗
PubMed2001

Recycling of petroleum-contaminated sand.

The environmental impact of using petroleum-contaminated sand (PCS) as a substitute in asphalt paving mixtures was examined. An appreciable component of PCS is oily sludge, which is found as the dregs in oil storage tanks and is also produced as a result of oil spills on clean sand. The current method for the disposal of oily sludge is land farming. However, this method has not been successful as an oil content of < 1% w/w is required, and difficulty was encountered in reaching this target. The reuse of the sludge in asphalt paving mixtures was therefore considered as an alternative. Standard tests and environmental studies were conducted to establish the integrity of the materials containing the recycled sludge. These included physical and chemical characterization of the sludge itself, and an assessment of the mechanical properties of materials containing 0%, 5%, 22% and 50% oily sludge. The blended mixtures were subjected to special tests, such as Marshall testing and the determination of stability and flow properties. The experimental results indicated that mixtures containing up to 22% oily sludge could meet the necessary criteria for a specific asphalt concrete wearing course or bituminous base course. To maximize the assay from the recycled material, the environmental assessment was restricted to the 50% oily sludge mixture. Leachates associated with this particular mixture were assayed for total organic residue and certain hazardous metal contaminants. The results revealed that the organics were negligible, and the concentrations of the metals were not significant. Thus, no adverse environmental impact should be anticipated from the use of the recycled product. Our research showed that the disposal of oily sludge in asphalt paving mixtures could possibly yield considerable savings per tonne of asphalt concrete, and concurrently minimize any direct impact on the environment.

Conservation of Natural Resources↗
PubMed2001

Isolation from Cussonia barteri of 1'-O-chlorogenoylchlorogenic acid and 1'-O-chlorogenoylneochlorogenic acid, a new type of quinic acid esters.

1'-O-Chlorogenoylchlorogenic acid and 1'-O-chlorogenoylneochlorogenic acid, a new type of quinic acid esters, have been isolated, in addition to six known quinic acid esters, rutin, and a mixture of saponins, from the methanol extract of Cussonia barteri Seemann (Araliaceae) leaves collected in Cameroon. Structure determination was achieved by NMR, mass, IR, and UV spectroscopy. All compounds were tested for inhibitory activity on 5-lipoxygenase and cyclooxygenase-1, for antimicrobial activity against Bacillus subtilis, Pseudomonas fluorescens, and Cladosporium cucumerinum, and for haemolytic activity.

Anti-Infective Agents↗
PubMed2001

Disparities in vegetable and fruit consumption: European cases from the north to the south.

OBJECTIVE: To present disparities in consumption of vegetables and fruits in Europe and to discuss how educational level, region and level of consumption influence the variation. DESIGN: A review of selected studies from 1985 to 1997. SETTING/SUBJECTS: 33 studies (13 dietary surveys, nine household budget surveys and 11 health behaviour surveys) representing 15 European countries were selected based on criteria developed as part of the study. Association between educational level and consumption of vegetables and fruits was registered for each study and common conclusions were identified. RESULTS: In the majority of the studies, with the exception of a few in southern and eastern Europe, consumption of vegetables and fruits was more common among those with higher education. The results suggest that in regions where consumption of vegetables and fruits is more common, the lower social classes tend to consume more of these than the higher social classes. CONCLUSIONS: The differences in the patterns of disparities in vegetable and fruit consumption between regions, as well as within populations, need to be considered when efforts to improve nutrition and health are planned.

Educational Status↗
PubMed2001

Diagnosis of renal cell carcinoma by bone marrow aspiration biopsy.

We report a patient who presented with persistent unclear fever, anaemia and leucopenia. A bone marrow aspiration biopsy was performed due to these symptoms, revealing malignant adenocarcinoma cells with a suspicion of renal origin. A computerized tomography confirmed the diagnosis. The patient progressed rapidly and died of widespread metastatic papillary renal cell carcinoma.

Biopsy, Needle↗
PubMed2001

Vanillic acid 4-O-beta-D-(6'-O-galloyl) glucopyranoside and other constituents from the bark of Terminalia macroptera Guill.et Perr.

A new phenolic glucoside gallate, vanillic acid 4-O-beta-D-(6'-O-galloyl) glucopyranoside (1) was isolated from the bark of Terminalia macroptera Guill.et Perr., together with 3,3',4'-tri-O-methylellagic acid (2) and two triterpene glucopyranosyl esters, 24-deoxysericoside (3) and chebuloside II (4). Compounds 2-4, not described previously for this plant, showed antimicrobial activities against Bacillus subtilis, while 3 and 4 possessed haemolytic properties. In both assays 1 was found to be inactive.

Bacillus subtilis↗
PubMed2001

Intratumoral variations in DNA ploidy and s-phase fraction in human breast cancer.

To study intratumoral DNA ploidy heterogeneity and S-phase fraction (SPF) variability, we prospectively collected five different samples from 48 breast carcinomas and each sample was analysed separately by flow cytometry. Aneuploidy rate was 89.6% after analysis of four or five samples. DNA ploidy heterogeneity, i.e., different samples classified as either DNA euploid or DNA aneuploid in the same tumor was seen in 17%, and DNA index heterogeneity, i.e., tumor populations with different DNA indices (DIs) seen in different samples was 44%. A statistical model defining SPF heterogeneity is proposed. SPF heterogeneity as defined by us was 71%, and as expected the SPF heterogeneity rate increased significantly with increasing number of analysed samples. Four or more samples are needed to detect the most deviant (highest) SPF values. An unrecognized intratumor heterogeneity of DNA ploidy and SPF may partly explain the conflicting results reported in the literature on the above prognostic indicators.

Breast Neoplasms↗
PubMed2000

Modulation of extracellular matrix adhesiveness by neurocan and identification of its molecular basis.

Neurocan is one of the major chondroitin sulfate proteoglycans of perinatal rodent brain. HEK-293 cells producing neurocan recombinantly show changes in their behavior. The expression of full-length neurocan led to a detachment of the secreting cells and the formation of floating spheroids. This occurred in the continuous presence of 10% fetal bovine serum in the culture medium. Cells secreting fragments of neurocan-containing chondroitin sulfate chains and the C-terminal domain of the molecule showed a similar behavior, whereas cells expressing fragments of neurocan-containing chondroitin sulfate chains but lacking parts of the C-terminal domain did not show spheroid formation. Cells secreting the hyaluronan-binding N-terminal domain of neurocan showed an enhanced adhesiveness. When untransfected HEK-293 cells were plated on a surface conditioned by spheroid-forming cells, they also formed spheroids. This effect could be abolished by chondroitinase treatment of the conditioned surface. The observations indicate that the ability of the chondroitin sulfate proteoglycan neurocan to modulate the adhesive character of extracellular matrices is dependent on the structural integrity of the C-terminal domain of the core protein.

Cell Adhesion↗
PubMed2000

Long-term cultured IL-2-dependent T cell lines demonstrate p16(INK4a) overexpression, normal pRb/p53, and upregulation of cyclins E or D2.

Acquisition of an immortal phenotype by circumvention of the normal senescence program can be an important step in tumor development and progression. The regulation of life-span checkpoints is complex and abrogation of these processes can occur at different levels. To better understand these mechanisms in long-term cultured lymphocytes we have characterized two human long-term cultured IL-2-dependent T cell lines regarding telomere length, telomerase activity, and the expression of selected cell cycle regulators (pRb, p53, cyclin E, cyclin D1, cyclin D2, cyclin D3, cdk4, p16(INK4a), p21(WAF1), p27(KIP1), c-myc, bcl-2, and NPAT). We compared these cell lines with a primary T lymphoblast population with a limited life span from the same donor. Both T cell lines with extraordinary growth capacity showed telomere length stabilization, high telomerase activity and demonstrated wild-type pattern of pRb and p53 but strong p16(INK4a) protein expression. The growth inhibitory activity of p16(INK4a) seemed to be abrogated by enhanced expression of cyclin D2, cdk4, and c-myc in one T cell line and overexpression of cyclin E in the second T cell line.

Cell Culture Techniques↗
PubMed2000

Telomere length and telomerase activity in malignant lymphomas at diagnosis and relapse.

Telomere length maintenance, in the vast majority of cases executed by telomerase, is a prerequisite for long-term proliferation. Most malignant tumours, including lymphomas, are telomerase-positive and this activity is a potential target for future therapeutic interventions since inhibition of telomerase has been shown to result in telomere shortening and cell death in vitro. One prerequisite for the suitability of anti-telomerase drugs in treating cancer is that tumours exhibit shortened telomeres compared to telomerase-positive stem cells. A scenario is envisioned where the tumour burden is reduced using conventional therapy whereafter remaining tumour cells are treated with telomerase inhibitors. In evaluating the realism of such an approach it is essential to know the effects on telomere status by traditional therapeutic regimens. We have studied the telomere lengths in 47 diagnostic lymphomas and a significant telomere shortening was observed compared to benign lymphoid tissues. In addition, telomere length and telomerase activity were studied in consecutive samples from patients with relapsing non-Hodgkin's lymphomas. Shortened, unchanged and elongated telomere lengths were observed in the relapse samples. The telomere length alterations found in the relapsing lymphomas appeared to be independent of telomerase and rather represented clonal selection random at the telomere length level. These data indicate that anti-telomerase therapy would be suitable in only a fraction of malignant lymphomas.

Humans↗
PubMed2000

Granulocytic sarcomas in body cavities in childhood acute myeloid leukemias with 11q23/MLL rearrangements.

Three childhood acute monoblastic leukemias (AML M5) with granulocytic sarcomas (GSs) are described. All displayed 11q23/MLL abnormalities, t(9;11)(p22;q23) in two cases and t(11;17)(q23;q21) in one case, constituting around 20% of all 11q23-positive AML cytogenetically investigated in our department. Two of the patients had GS in multiple locations, and all three had abdominal GS. In two of them, t(9;11)-positive GS was diagnosed prior to the diagnosis of AML. Fourteen (1.9%) of 752 published AML cases with 11q23 aberrations have had GS, either as a presenting feature or during disease progression. The incidence of GS has varied significantly (P < 0.05) between children (3.8%) and adults (0.8%). The most common AML subtype has been AML M5 ( approximately 75%) and the most frequent GS sites have been the skin, abdomen, orbit, and thorax. Considering the possibility of underreporting of GS in published cases and the relatively high frequency in our own series, we believe that 11q23/MLL rearrangements may predispose to GS development. Although extramedullary infiltrates in the skin are known to be frequent in cases of AML M5, which is often associated with 11q23 aberrations, the present findings indicate that GS in the abdomen, orbit, and thorax may also be common, especially in pediatric AML. Thus, the possibility of 11q23/MLL-positive GS should be suspected when tumors of uncertain derivation occur in these sites. Finally, the identification of 11q23/MLL abnormalities in GSs in two patients without overt AML underscores the importance of using cytogenetic and molecular genetic investigations as a diagnostic approach in the evaluation of tumorous lesions of unknown origin. Genes Chromosomes Cancer 27:136-142, 2000.

Abdomen↗
PubMed2000

Adenovirus-mediated overexpression of p15INK4B inhibits human glioma cell growth, induces replicative senescence, and inhibits telomerase activity similarly to p16INK4A.

The genes encoding the cyclin-dependent kinase inhibitors p16INK4A (CDKN2A) and p15INK4B (CDKN2B) are frequently homozygously deleted in a variety of tumor cell lines and primary tumors, including glioblastomas in which 40-50% of primary tumors display homozygous deletions of these two loci. Although the role of p16 as a tumor suppressor has been well documented, it has remained less well studied whether p15 plays a similar growth-suppressing role. Here, we have used replication-defective recombinant adenoviruses to compare the effects of expressing wild-type p16 and p15 in glioma cell lines. After infection, high levels of p16 and p15 were observed in two human glioma cell lines (U251 MG and U373 MG). Both inhibitors were found in complex with CDK4 and CDK6. Expression of p16 and p15 had indistinguishable effects on U251 MG, which has homozygous deletion of CDKN2A and CDKN2B, but a wild-type retinoblastoma (RB) gene. Cells were growth-arrested, showed no increased apoptosis, and displayed a markedly altered cellular morphology and repression of telomerase activity. Transduced cells became enlarged and flattened and expressed senescence-associated beta-galactosidase, thus fulfilling criteria for replicative senescence. In contrast, the growth and morphology of U373 MG, which expresses p16 and p15 endogenously, but undetectable levels of RB protein, were not affected by exogenous overexpression of either inhibitor. Thus, we conclude that overexpression of p15 has a similar ability to inhibit cell proliferation, to cause replicative senescence, and to inhibit telomerase activity as p16 in glioma cells with an intact RB protein pathway.

Adenoviridae↗
PubMed1999

Application of high-performance liquid chromatography coupled to nuclear magnetic resonance spectrometry, mass spectrometry and bioassay for the determination of active saponins from Bacopa monniera Wettst.

Reversed-phase high-performance liquid chromatographic separation coupled to (structurally informative) spectroscopic methods like NMR and MS and an efficient bioassay have been used to determine the active compounds from a crude fraction of Bacopa monniera. The fraction containing a mixture of saponins with closely related structures was found to show a significant anthelmintic activity against Caenorhabditis elegans (used as a model test organism for determining anthelmintic activity). The activity was correlated to two dammarane type triterpenoidal saponins containing at least three sugar units. The optimization of separation for 1 mg of the crude sample on column and the sensitivity of on-flow one- and two-dimensional NMR experiments to the high-molecular-mass compounds (M(r) 890-930) has been demonstrated.

Animals↗
PubMed1999

Cyclin-D1 expression in human renal-cell carcinoma.

Cyclin-D1 over-expression represents one of several common alterations in the G1-S transition associated with malignancies. Conclusive evidences indicate that cyclin D1 is a proto-oncogene and the gene is amplified or rearranged in different tumour types. Since very little is known about aberrations in the G1-S transition in human renal-cell carcinoma (RCC), we have characterized the expression of cyclin D1 in 80 human renal-cell carcinomas and 12 normal kidney cortex tissues using Western blotting. The cyclin-D1-protein content varied considerably and 75% of the tumours expressed higher levels than normal kidney cortex, in contrast to 25% of the tumours either lacking cyclin D1 or with low protein levels. Although it is difficult to define aberrant expression of cyclin D1, the results might indicate that the proto-oncogene was activated in a sub-set of RCC. It is also possible that low expression of cyclin D1 represents an aberrant down-regulation of the protein. Immunohistochemical assessment of cyclin D1 in a sub-set of the tumours showed large variations in the fraction of cyclin-D1-positive cells, supporting the Western-blot analyses. Surprisingly, cyclin-D1 expression did not correlate with proliferation determined by Ki-67-antigen expression or S-phase analyses. In non-papillary renal-cell carcinomas, high cyclin-D1 expression was associated with a diploid DNA profile and smaller tumour size, but there was no association between cyclin-D1 expression and tumour stage or nuclear grade. In nonpapillary tumours, high cyclin-D1 expression was further significantly associated with a better prognosis according to univariate and multivariate analyses (p = 0.005 and 0.002 respectively), as compared with highly aggressive tumours with low cyclin-D1 levels.

Adult↗
PubMed1999

Cyclin E dependent kinase activity in human breast cancer in relation to cyclin E, p27 and p21 expression and retinoblastoma protein phosphorylation.

The cell cycle machinery is regulated by cyclin dependent kinases and sets of activating and inhibitory proteins. The G1-S control mechanism is often deregulated in tumours supposedly leading to increased kinase activity, phosphorylation of substrates and subsequent S phase entrance. Increased kinase activity has been proposed to be essential in cell cycle aberrations, but few studies have actually shown enhanced kinase activity related to specific cell cycle defects in primary tumours. In the present study we have determined the cyclin E dependent kinase activity (cyclin E(kinase)) in 59 primary breast cancers, using an H1-kinase assay, and related the activity to the expression of cyclin E, p27 and p21. In a subgroup of 48 tumours, we further characterized the association between cyclin E(kinase), in vivo phosphorylation of the retinoblastoma protein (pRb) and proliferation. The cyclin E(kinase) correlated significantly with cyclin E content and inversely with p27 and p21 expression. P27, but not p21, was associated with low cyclin E(kinase) in specimens with normal/low levels of cyclin E. At elevated cyclin E levels, suppression of cyclin E(kinase) seemed to require high levels of both p21 and p27. The cyclin E(kinase) correlated with the phosphorylation status of pRb as well as with proliferation. Surprisingly, pRb phosphorylation did not correlate with proliferation. Our results support that pRb is a substrate for cyclin E(kinase) in primary breast cancer and that deregulation of cyclin E and p27 act through increased CDK-kinase activity, but cyclin E associated events beside pRb phosphorylation might be rate-limiting for entrance into S phase.

Breast Neoplasms↗