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M Pauly

Publications and source records attributed to M Pauly.

At least 37 records · Page 2Linked to original sources
PubMed1997

Ki-ras oncogene and p53 tumour suppressor gene mutations in colorectal carcinomas from the European Saar-Luxembourg region are less frequent than predicted by the classic adenoma-carcinoma sequence model.

Recent investigations of colorectal cancer (CRC) have suggested that the accumulation of specific alterations in cell-growth regulating genes trigger the stage-wise progression to malignancy and that at least some of them could be useful for prognosis. In this study, the frequency, location and type of mutations of the Ki-ras proto-oncogene exons 1-2 and p53 tumour-suppressor gene exons 5-9 were analysed in colorectal carcinomas of 72 patients from the European Saar-Luxembourg region using PCR-SSCP screening and direct sequencing. The incidences of Ki-ras activating and p53 inactivating point mutations in these European samples were much lower (Ki-ras: 5 (6.9%) and p53: 13 (18.1%)) than reported for both genes in American studies (40-50% at least) (P < 1 x 10(-3)). These results suggest that other genetic mechanisms than those proposed for the classic adenoma-carcinoma sequence model can frequently underlie CRC development and that Ki-ras and p53 mutations should not be considered as universal markers for CRC.

Adenoma↗
PubMed1997

Multidrug resistance: molecular and clinical aspects.

Clinical drug resistance, a common and compromising side-effect during anticancer chemotherapy, is an acquired cellular resistance simultaneously to several cytotoxic drugs. Expression of the multidrug resistance gene (mdr) is one of the most-studied potential underlying mechanisms. The human mdr gene family encompasses two homologous members, the first of which, called the mdr1 gene, is the best-characterized so far. The human mdr1 gene has been shown to encode a membrane P-170 glycoprotein that, on the basis of its structure, is considered to act as a drug-efflux pump excreting various drugs from cells. The human mdr1 gene is thus a major regulated gene playing an important role in the molecular mechanism of multidrug resistance. Its bipartite structure of two similarly organized halves is explained by a gene fusion event during evolution. However, the clinical significance of this particular feature, if it seemed obvious in the 1980s as a factor producing chemoresistance, is currently revised-being a marker of tumor aggressiveness rather than the cause of drug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Substitution of L-fucose by L-galactose in cell walls of Arabidopsis mur1.

An Arabidopsis thaliana mutant (mur1) has less than 2 percent of the normal amounts of L-fucose in the primary cell walls of aerial portions of the plant. The survival of mur1 plants challenged the hypothesis that fucose is a required component of biologically active oligosaccharides derived from cell wall xyloglucan. However, the replacement of L-fucose (that is, 6-deoxy-L-galactose) by L-galactose does not detectably alter the biological activity of the oligosaccharides derived from xyloglucan. Thus, essential structural and conformational features of xyloglucan and xyloglucan-derived oligosaccharides are retained when L-galactose replaces L-fucose.

2,4-Dichlorophenoxyacetic Acid↗
PubMed1996

Improved protocol for the formation of N-(p-nitrobenzyloxy)aminoalditol derivatives of oligosaccharides.

An improved procedure has been developed for the rapid derivatization of oligosaccharides with UV-detectable p-nitrobenzylhydroxylamine (PNB). The improved conditions used result in quantitative derivatization of neutral oligosaccharides. Sialylated oligosaccharides can also be quantitatively PNB-derivatized without detectable desialylation. Of the oligosaccharides tested, only the derivatization of oligogalactosyluronic acids was incomplete (yield approximately 70%). PNB-derivatization of tamarind seed xyloglucan oligosaccharides results in products with improved chromatographic properties during HPAEC. These PNB derivatives were also subjected to hydrophilic interaction chromatography (HILIC) and analyzed by on-line LC-MS. On-line LC-MS is readily usable with HILIC, as this chromatographic technique does not require salt-containing solvents. Approximately 10 pmol of a PNB-derivatized oligosaccharide can be identified and quantitated utilizing this method.

Carbohydrate Conformation↗
PubMed1995

Metabolism of xyloglucan generates xylose-deficient oligosaccharide subunits of this polysaccharide in etiolated peas.

Oligosaccharide subunits of xyloglucan were isolated from the stems and roots of etiolated pea plants and structurally characterized. The two most abundant subunits of pea xyloglucan are the well-known nonasaccharide, XXFG, and heptasaccharide, XXXG. In addition, significant amounts of oligosaccharides that have not previously been reported to be subunits of pea xyloglucan were detected, including a decasaccharide, XLFG, two octasaccharides, XLXG and XXLG, a pentasaccharide, XXG, and a trisaccharide, XG. Several novel oligosaccharide subunits, including the octasaccharide, GXFG, and the hexasaccharide, GXXG, were also found. Xyloglucan oligosaccharides generated by treatment of intact pea stem cell walls were compared to oligosaccharides generated by endoglucanase treatment of xyloglucan polysaccharides obtained by subsequent alkali extraction of the same cell walls. The results suggest that the xyloglucan in etiolated pea stems is distributed between at least two domains, one of which is distinguished by its enzyme accessibility. We further hypothesize that the chemical modification of a xyloglucan during cell-wall maturation depends on its physical environment (i.e., the domain in which it resides). For example, only the endoglucanase-released material, representing the enzyme-accessible xyloglucan domain, contains significant amounts of the two unusual oligosaccharide subunits, GXXG and GXFG, both of which have a nonreducing terminal glucosyl residue. This structure may be generated during cell-wall maturation by the sequential action of an endolytic enzyme (such as xyloglucan endotransglycosylase or endoglucanase) and an alpha-xylosidase.

Carbohydrate Sequence↗
PubMed1995

The human mdr1 (multidrug-resistance) gene harbours a long homopyrimidine.homopurine sequence next to a cluster of Alu repeated sequences in intron 14.

In order to identify specific DNA sequences useful as 'genetic landmarks' in the construction of a complete map of the human mdr1 (multidrug-resistance) gene, we investigated the introns in the central region. In intron 14, we identified a long stretch of a homopyrimidine.homopurine sequence most probably adopting an unconventional DNA conformation, followed by a cluster of three Alu repeated sequences in an inverted orientation. Here, we describe the structure, formation and nucleotide sequence of these DNA elements.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Repetitive DNA sequences located in the central region of the human mdr1 (multidrug resistance) gene may account for a gene fusion event during its evolution.

The mdr1 gene, first member of the human multidrug-resistance gene family, is a major gene involved in cellular resistance to several drugs used in anticancer chemotherapy. Its product, the drug-excreting P-glycoprotein, shows a bipartite structure formed by two similar adjacent halves. According to one hypothesis, the fusion of two related ancestral genes during evolution could have resulted in this structure. The DNA sequence analysis of the introns located in the region connecting the two halves of the human mdr1 gene revealed a highly conserved poly(CA).poly (TG) sequence in intron 15 and repeated sequences of the Alu family in introns 14 and 17. These repeated sequences most likely represent "molecular fossils" of ancient DNA elements which were involved in such a recombination event.

Base Sequence↗
PubMed1994

Hydrophilic-interaction chromatography of complex carbohydrates.

Complex carbohydrates can frequently be separated using hydrophilic-interaction chromatography (HILIC). The mechanism was investigated using small oligosaccharides and a new column, PolyGLYCOPLEX. Some carbohydrates exhibited anomer separation, which made it possible to determine the orientation of the reducing end relative to the stationary phase. Amide sugars were consistently good contact regions. Relative to amide sugars, sialic acids and neutral hexoses were better contact regions at lower levels of organic solvents than at higher levels. HILIC readily resolved carbohydrates differing in residue composition and position of linkage. Complex carbohydrate mixtures could be resolved using volatile mobile phases. This was evaluated with native glycans and with glycans derivatized with 2-aminopyridine or a nitrobenzene derivative. Both asialo- and sialylated glycans could be resolved using the same set of conditions. With derivatized carbohydrates, detection was possible at the picomole level by UV detection or on-line electrospray mass spectrometry. Selectivity compared favorably with that of other modes of HPLC. HILIC is promising for a variety of analytical and preparative applications.

Animals↗
PubMed1994

Comprehensive discharge planning for the hospitalized elderly. A randomized clinical trial.

OBJECTIVE: To study the effects of a comprehensive discharge planning protocol, designed specifically for the elderly and implemented by nurse specialists, on patient and caregiver outcomes and cost of care. DESIGN: Randomized clinical trial. SETTING: Hospital of the University of Pennsylvania. PATIENTS: 276 patients and 125 caregivers. Patients were 70 years and older and were placed in selected medical and surgical cardiac diagnostic-related groups. MEASUREMENTS: Group differences in patient outcomes (length of initial hospital stay, length of time between initial hospital discharge and readmission, and rehospitalization rates) and charges for care (charges for initial hospitalization, rehospitalizations, health services after discharge, and nurse specialist services) were measured 2, 6, and 12 weeks after discharge. RESULTS: From the initial hospital discharge to 6 weeks after discharge, patients in the medical intervention group had fewer readmissions, fewer total days rehospitalized, lower readmission charges, and lower charges for health care services after discharge. No differences in these outcomes were found between the surgical intervention and control groups during this period. CONCLUSIONS: Study findings support the need for comprehensive discharge planning designed for the elderly and implemented by nurse specialists to improve their outcomes after hospital discharge and to achieve cost savings. The findings also suggest that this intervention had its greatest effect in delaying or preventing rehospitalization of patients in the medical intervention group during the first 6 weeks after discharge.

Aged↗
PubMed1992

The initiation accuracy of the SV40 early transcription is determined by the functional domains of two TATA elements.

To locate the boundaries of the TATA element in the SV40 early promoter, point mutations have been constructed such as to cover the whole T + A-rich region of the replication origin. The effects of these mutations on the rate of transcription in vivo show that this region actually contains two TATA elements I and II, each independently directing the accurate initiation of transcription from a specified set of start sites, EES1 and EES2, respectively. The sequence of TATA element I fits best with the compiled 'consensus' sequence found in eukaryotic gene promoters and is the most efficient in directing transcription initiation. Mutations which improve this fit can still increase the rate of transcription, confirming the theory of a correlation between the nucleotide sequence of a TATA element and its functional efficiency. Moreover, some mutations which simultaneously modify the angle of DNA curvature in the T + A-rich promoter region and the rate of transcription reveal a correlation between DNA bending and transcription initiation.

Base Sequence↗
PubMed1992

Genetic aspects of multidrug resistance.

Gene amplification is responsible both for dihydrofolate reductase induced methotrexate resistance, and for the P-glycoprotein encoding multigene family induced multidrug resistance. The 6 pairs of hydrophobic regions of the P-glycoprotein fold up in a snake-like structure through the lipidic layers of the cell membrane. Other detoxification mechanisms include the glutathione S-transferase 'pi', but without gene amplification.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

The genetic basis of multidrug resistance.

Cellular multidrug resistance, a common side-effect of anticancer chemotherapy frequently leading to failure of the treatment, has been characterized as an acquired resistance to several antimitotic drugs simultaneously. Multidrug resistance could mainly be attributed to the overexpression of the P-170 glycoprotein, considered as a drug-efflux pump encoded by the mdr 1 gene. Overexpression of this protein can be induced either by an accidental amplification or activation or both of the mdr 1 gene. Recent investigations focused on these mechanisms, aiming at a better understanding of the appearance of multidrug resistance during a chemotherapy. P-glycoprotein mediated drug resistance, however, is only one, albeit quite an important detoxification pathway, and some observations revealed genetic interactions with other systems. On the basis of this new knowledge, the development of novel therapeutic strategies to circumvent this clinical side-effect of cancer treatment has already begun.

Antineoplastic Agents↗
PubMed1991

Impact of Phase I Pew National Dental education Program on U.S. schools of dental medicine.

This paper presents the results of four telephone surveys conducted by the Leonard Davis Institute of Health Economics (LDI), University of Pennsylvania, as part of its evaluation of the Pew National Dental Education Program (PNDEP), a five year, +4F8.7 million program established by The Pew Charitable Trusts to help dental schools respond to the changing health care environment. The four annual surveys were conducted between 1985 and 1988. The interviews were conducted with the deans from nearly all dental schools operating in the United States at the time of study or the principal investigators of the schools funded under Phase I and Phase II PNDEP grants. Their purpose was to determine the level of each school's involvement in PNDEP and in specific strategic planning activities, as well as to evaluate the impact of the Pew Program on both the individual schools and dental education nationwide. All systematic differences between schools funded (FD) PNDEP and those not funded (NFD) were examined. Overall, schools gained a better understanding of their environment. Schools also reported increased participation in and commitment to planning among their different constituencies (e.g., faculty, administration, students, alumni). By the end of Phase I, more PNDEP Phase I funded schools reported being involved in implementing strategic plans. Funded schools also were more likely to report PNDEP increased their understanding of strategic planning, improved communication, and helped encourage the emergence of new leaders.

Administrative Personnel↗
PubMed1990

The regulation of gene expression and the molecular basis of cancer.

Over the last few years, the advent of new genetic techniques allowed a detailed analysis of the structural and functional organization of the genome and the genes in a living cell. After the discovery of cellular oncogenes, genes which are implicated in cell growth control and differentiation, recent investigations provided evidence to a crucial role played by certain gene regulatory DNA elements and oncoproteins in the molecular mechanisms of carcinogenesis.

Cell Transformation, Neoplastic↗
PubMed1987

Colonoscopic therapy of acute pseudoobstruction of the colon.

All patients with the diagnosis of acute colonic pseudoobstruction at the University of California, Davis Medical Center from 1979-1985 were reviewed. These 25 patients were initially treated conservatively (nasogastric tube/rectal tube/enemas) and this was successful in eight of 25 patients (32%). The remaining 17 patients (68%) unresponsive to conservative therapy received endoscopic intervention, either colonoscopic suction decompression (CSD) or colonic suction decompression with proximal colonic tube placement (CDT) for continuous decompression. Of the endoscopic procedures performed, 13/17 (76%) resulted in successful acute decompression. Recurrences occurred in 6/13 (45%) (3/7 in the colonoscopic suction decompression group and three of six in the colonic tube placement group). In the 10 failures, six further procedures were attempted, but only one was successful. These patients were then treated conservatively. There were no instances of colonic perforation. Acute pseudoobstruction in our experience is a benign entity that can be safely and successfully treated nonsurgically. Colonoscopic suction decompression is often initially successful but has a high frequency of recurrence. Newer techniques to prevent recurrence, i.e., colonic tube placement, are of potential benefit but presently have technical problems.

Acute Disease↗