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Biomedical subjects

N Vogt

Publications and source records attributed to N Vogt.

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

DNA hypomethylation in breast cancer: an independent parameter of tumor progression?

The global DNA methylation status was investigated on a series of 59 breast cancers by Southern blotting, using methylation sensitive restriction enzymes. By comparison to control DNA, almost all tumor DNAs were found globally hypomethylated. However, the demethylation was variable from tumor to tumor. Compared to other biological parameters, the methylation did not correlate with chromosome alterations, steroid hormone receptor status, or histopathological grading. Tumors which appeared to be the most evolved for other parameters were only mildly hypomethylated, whereas tumors with strongly hypomethylated DNA corresponded to those with slight alterations of the other parameters. Thus, DNA hypomethylation is a consistent characteristic of breast cancer, but its variations may not correlate with tumor progression of most breast cancers.

Age Factors↗
PubMed1996

Structural heterogeneity of hsr(11) in the MDA-MB-134 mammary carcinoma cell line.

The MDA-MB-134 cell line was characterized by the presence of two homogeneously staining region (hsr) carrier chromosomes containing sequences from 8p11-p12, 11q13, and 8q24. Using fluorescence in situ hybridization, a detailed study of the organization of this chromosome has been performed. The hsr carrier chromosomes are shown to be identical and to derive from a chromosome 11, on which large segments of the long arm of chromosome 8 are translocated, forming its short arm. The hsr segment is inserted in the long arm, distally to C1NH gene. It is formed by sequences from both chromosomes 8 and 11. For the genes investigated by both methods the number of copies detected by in situ hybridization is compatible with that expected by quantification of Southern blots. In spite of its complexity, a possible mechanism of formation is proposed.

Breast Neoplasms↗
PubMed1995

DNA-repeat instability is associated with colorectal cancers presenting minimal chromosome rearrangements.

The DNA-repeat [(CA)n] instability of colorectal cancer cells was studied relative to our previously defined classification based on chromosome alterations. Of the 23 tumors analyzed, 13 belonged to the "monosomic" type (MT) characterized by simultaneous loss of chromosome 18 and chromosome arm 17p, and many structural rearrangements, 7 to the "trisomic" type (TT) with many chromosome gains but few rearrangements, and 3 had a normal karyotype (NT). (CA)n repeat sequences were examined on chromosomes 2, 5, 11, 13, 18, and 20. We found sequence alterations in 12 tumors at 1 or several loci, 9 of which (1/13 MT, 5/7 TT, and 3/3 NT) exhibited a typical shift in allele size defined as microsatellite instability. Furthermore, a single alteration was observed for the MT tumor, whereas one NT tumor displayed instability on two and all the other tumors on three or more loci. These results suggest an inverse relationship between the occurrence of chromosome structural rearrangements and microsatellite instability, providing another argument for the subdivision of colorectal cancers into groups of distinct oncogenic pathways.

Adult↗
PubMed1995

Characterization and chromosomal location of two repeated DNAs in three Gerbillus species.

Two tandemly repeated DNA sequences of Gerbillus nigeriae (Rodentia) (GN1 and GN2) were isolated and characterized. Both share a 36bp repeated unit, which includes a 20bp motif also found in primate alphoid and other repeated DNAs. The localization of GN1 and GN2 sequences on metaphase chromosomes of three Gerbillus species, G. nigeriae, G. aureus and G. nanus, was studied by fluorescence in situ hybridization (FISH). In the G. nigeriae and G. aureus karyotypes, which were shown to possess large amounts of heterochromatin and to have undergone multiple rearrangements during evolution, both GN1 and GN2 sequences were observed at various chromosomal sites: centromeric, telomeric and intercalary. In contrast, the karyotypically stable G. nanus, which does not possess large amounts of heterochromatin and seems to be a more ancestral species, possesses only GN1 sequences, localized in the juxtacentromeric regions.

Animals↗
PubMed1995

In vivo inhibition profile of cytochrome P450TB (CYP2C9) by (+/-)-fluvastatin.

BACKGROUND: (+/-)-Fluvastatin is a synthetic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor that selectively and competitively inhibits P450TB (CYP2C9) in vitro. The potential for kinetic interactions in vivo between fluvastatin and P450TB substrates was therefore investigated in healthy volunteers. METHODS: Diclofenac (25 mg orally) oxidation was used as a marker of P450TB activity on days 0, 1, and 8 of fluvastatin treatment (40 mg/day). RESULTS: Diclofenac peak concentration (Cmax) increased over time (0.28 [SD, 0.12], 0.38 [0.20], and 0.45 [0.4] mg/L on days 0, 1, and 8, respectively). Oral clearance was reduced on days 1 and 8 (14% and 15%, respectively). A time-dependent decrease in urinary metabolic ratio (MR, 4'-hydroxydiclofenac/diclofenac) was noted (1.07 [0.34], 0.90 [0.23] and 0.70 [0.18] on days 0, 1, and 8, respectively [p < 0.0001]) for the first 4 hours. The interaction was clear in only some individuals; MR reduction was related to baseline MR and it was more pronounced in subjects with a higher baseline MR (p < 0.01). Fluvastatin Cmax (0.18 [0.11] and 0.32 [0.1] mg/L on days 1 and 8, respectively) and area under the curve (0.28 [0.12] and 0.43 [0.15] hr.mg/L on days 1 and 8, respectively; p < 0.001) increased over time. Diclofenac MR reduction was correlated with fluvastatin concentrations. CONCLUSIONS: Interactions between fluvastatin and P450TB substrates (phenytoin, oral anticoagulants, oral hypoglycemic agents, and nonsteroidal antiinflammatory drugs) may occur, at least in some patients.

Adult↗
PubMed1994

[Clinical pharmacology in practice].

A university-hospital clinical pharmacology consult service was evaluated for: spontaneous use by clinicians (reflecting the competence conferred to clinical pharmacologists and the information clinicians seek), subject matters of postgraduate teaching to internal medicine trainees (needs perceived by the clinical pharmacologist), and finally, prescription profile of these trainees (clinical reality). Over 14 months, 663 requests were received (86% for a specific patient). Topics included adverse events (AE) (53%), pharmacokinetics (PK) (20%), treatment indications (T) (19%), and product identification (Id) (8%). In the service holding regular teaching sessions in clinical pharmacology, spontaneously requested consults pertained to: T 49% (mainly pain management, a domain of expertise of this particular clinical pharmacology service), AE 34%, PK 12% and Id 5%. In contrast, teaching covered PK 42%, T 39% (half on pain), and AE 16% of the time. The prescription profile included 201, mostly elderly patients, 40% with an estimated creatinine clearance < or = 50 ml/min. Of the renally compromised patients, only 14% were clearly identified as such by the doctor in charge, although 63% received at least one drug requiring dosage adjustment, which was done in 44% of cases. Interactions were present in 9% of treatments, which were appropriately adjusted in two thirds following routine in-hospital monitoring of low therapeutic index drugs, even though the possibility of an interaction was not explicitly charted. In conclusion, despite increasing complexity of therapeutics, reliance on clinical pharmacologists is variable.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

[Evaluation of chronic pain in geriatric patients].

This retrospective study considers the influence of chronological age on the perception and consequential effects of chronic non-cancer pain in 203 patients referred to an ambulatory pain clinic. One patient in four (50) was 65 years or older. Pain had existed for more than a year in 66%. It was referred to an "unbearable" by 54% of elderly adults vs 44% (NS) of the younger adult population, and as "intense" by 61% vs 44% (p < 0.05). A higher proportion of neurogenic pain (54% vs 26%, p < 0.05) could explain this significant difference. Cognitive factors could also have amplified the painful syndrome since 59% (vs 54%) of the elderly considered they had received insufficient information on the potential consequences of their painful condition. However, despite a higher occurrence of other severe illnesses in the elderly (52% vs 35%, p < 0.05), they appear to worry less about their health problems (58% vs 78%, p < 0.01). Finally, in spite of increased severity of pain in the elderly, depression scores and consequential effects are similar in the two populations. In conclusion, the intensity of chronic pain appears to be more severe in the elderly, perhaps due to its more frequent neuropathic origin. Nonetheless, its repercussions on daily life activity seem no worse than for younger adults, and could reflect better coping strategies towards chronic pain.

Activities of Daily Living↗
PubMed1994

Skewed inactivation of an X chromosome deleted at the dystrophin gene in an asymptomatic mother and her affected daughter.

A girl with severe Becker muscular dystrophy and apparently normal chromosomes had a heterozygous deletion for exons 51, 52, and 53 of the dystrophin gene. This deletion was transmitted by her mother, who was unaffected. To differentiate the normal and the deleted X chromosomes, fluorescence in situ hybridization (FISH) was applied to metaphase chromosomes, using probes for both exons 51 and 52, which are only 388 and 113 base pairs long, respectively. FISH signals were observed in one or both chromatids of one chromosome, but never on both chromosomes, suggesting the lack of hybridization on the deleted X chromosome. Using 5-bromodeoxyuridine incorporation to differentiate the late (inactive) and the early replicating (active) X chromosomes, 77% of the signals were observed on the active X chromosomes in the mother. This percentage was only 18% in the daughter, suggesting that skewed inactivation of the X chromosomes was responsible for the phenotypic differences.

Adolescent↗
PubMed1994

[Comparison of 5% human albumin and 6% 200/0.5 HES as exclusive colloid components in large surgical interventions].

OBJECTIVE: It was the purpose of the following study to compare effects of 6% hydroxyethyl starch 200/0.5 (HES) and albumin 5% (HA5) on haemostasis, haemodynamics, oncotic function and plasmatic homoeostasis. METHODS: In 2 randomised groups of 20 patients each undergoing large surgery (criteria of exclusion: anaemia, renal, liver, and coagulation disorders, ASA classification > III) we treated up to 1000 ml with colloid solution, from 1000 ml up to 5000 ml with packed red blood cells (PRBC) and colloid solution (1:1) and above 5000 ml with PRBC and fresh frozen plasma (1:1). Group HES received HES and group HA5 albumin as exclusive colloid component and both continuously lactated Ringers' at a rate of 500 ml/h. We measured the parameters before operation, after each 1000 ml colloid up to 3000 ml application and at the end of operation and we registered total blood output/intake. RESULTS: We found comparable amounts of blood loss and blood intake (mean total amount of colloid solution: HES 2044 +/- 579 ml; HA5 2547 +/- 980 ml). We didn't find any differences in haemodynamics nor in haematocrit, platelets or global coagulation parameters which only showed dilutional influences. Differences existed in total serum protein (HES 32.8 +/- 6.5 gr/l; HA5 54 +/- 5.5 gr/l at OP's end); however COP was maintained in both groups during the whole study period at normal ranges. Plasmatic haemostasis showed to a large extent corresponding values. Remarkable was the development of a metabolic acidosis in the HA5 group. CONCLUSION: Regarding total blood output/intake, haemodynamic functions, haematological parameters, coagulation, oncotic function, and plasmatic homoeostasis, HES is a safe colloid if contra-indications are taken into account, capable of replacing albumin 5% entirely as a colloid component of treatment of even large blood losses intraoperatively above the recommended dose of 20 ml/kg BW/d.

Adult↗
PubMed1994

Increased FISH efficiency using APC probes generated by direct incorporation of labeled nucleotides by PCR.

Probes of various sizes from the adenomatous polyposis coli gene (APC) were directly biotinylated by polymerase chain reaction (PCR) from genomic DNA. PCR labeling gave high efficiency in detection of fluorescence in situ hybridization (FISH) signals. Probes as small as 250 base pairs could be visualized through a fluorescence microscope without any image processing.

Adenomatous Polyposis Coli↗
PubMed1994

In situ hybridization approach at infragenic level on metaphase chromosomes.

Analysis of the retinoblastoma locus (RB1) by in situ hybridization at the infragenic level was done using human chromosomes. A high level of resolution was attained with nonisotopic in situ hybridization on banded chromosomes in both fluorescence and electron microscopy. DNA sequences less than 100 kb apart could be positioned on band 13q14 in the order expected from molecular mapping. These observations suggest that the DNA target of hybridized probes on metaphase chromosomes may correspond to nucleoprotein loops giving a resolution comparable to that obtained in interphase nuclei.

Genes, Retinoblastoma↗
PubMed1993

[Drug prices in Switzerland: European comparison of "comfort" drugs].

We compared the average Swiss prices of so-called "comfort medicines" with the prices operating in several other European countries. These drugs, which are numerous in Switzerland, were defined as having no demonstrable efficacy or as being prescribed for physiopathological entities of uncertain scientific basis. The comparison shows that the average price of comfort medicines in Switzerland is not different from the German price (-17%, ns), but is higher than in Sweden (+35%, p < 0.05), France (+61%, p < 0.01) and Italy (+65%, p < 0.01). Furthermore, the average price of innovative new chemical entities is strongly correlated with that of the comfort medicines in all the countries considered and despite the vastly different therapeutic value of these two categories of drugs.

Drug Costs↗
PubMed1992

Secondary pyeloureterostomy after ureter necrosis in renal transplant recipients.

After kidney transplantation, urological complications account for significant morbidity necessitating reoperation in a substantial number of patients. In cases with urinary tract necrosis after renal transplantation secondary pyeloureterostomy represents an accepted method for urinary tract reconstruction. In our institution 2% of all kidney grafts required secondary pyeloureterostomy. In all cases the recipient's own ureter was investigated before reoperation by retrograde pyeloureterography. Pyeloureterostomy was performed with a standard technic, the recipients own kidney being removed in all but 5 patients. All 25 patients had normal kidney function immediately after secondary pyeloureterostomy. Urological complications occurred in 7 patients (anastomotic leakages in 4, stenosis in 3); 5 out of 7 complications were managed conservatively (nephrostomy, transureteral stenting). Two patients needed reexploration for reanastomosis. Our results confirm the simple and safe technic of pyeloureterostomy for urinary reconstruction in patients with ureter necrosis after renal transplantation.

Adult↗
PubMed1992

Influence of the pH-value on the growth of Staphylococcus epidermidis, Staphylococcus aureus and Propionibacterium acnes in continuous culture.

A cutaneous isolate of Staphylococcus epidermidis, Staphylococcus aureus and Propionibacterium acnes was grown in continuous culture at varying pH-values ranging from 5.0 to 8.5. In terms of the specific growth rate as well as the bacterial density during the plateau phase there were remarkable differences. In particular, Propionibacterium acnes grew much better in the pH 6.0 to 7.0 range than in a more acidic or alkaline milieu. Staphylococcus epidermidis resembled Staphylococcus aureus showing no major difference at pH 5.5 and 7.0. These findings substantiate the hypothesis that minor changes of the pH in the pH 5.5 to pH 6.0 range as to be induced by chemically neutral or alkaline skin cleansers on the human skin surface can increase the number of propionibacteria but not staphylococci remarkably due to the relative alkalinity by itself.

Culture Media↗
PubMed1989

The E2 trans-activating protein of bovine papillomavirus type 1 (BPV1) is serine-phosphorylated in vivo.

The E2 open reading frame of bovine papillomavirus 1 (BPV1) encodes both positive and negative transcriptional regulatory factors. The full-length E2 gene polypeptide is a strong transcriptional transactivator that acts on enhancers within the papillomavirus long control region (LCR), and two shorter E2 proteins function as transcription repressors. A vaccinia recombinant virus harboring the full length E2 coding sequence of BPV1 directs the synthesis of a 48 kD phosphoprotein with specific DNA binding activity. We show that in BPV1-transformed cells the full-length transactivator is a phosphoprotein, whereas truncated E2 proteins were not detectably phosphorylated.

Amino Acids↗
PubMed1988

A study of the B-Z transition of the AC-rich region of the repeat unit of a satellite DNA from Cebus by means of chemical probes.

The conformational changes induced by negative supercoiling in the AC-rich region of the repeat unit of a Cebus satellite DNA has been studied by chemical probes sensitive to alterations in DNA conformation. This region is constituted of a (GT/CA)n stretch (15 less than or equal to n less than or equal to 18) associated to a sequence rich in GT/CA. At high superhelical density, at least 100 base pairs in the AC-rich region adopt the Z conformation as judged by diethyl pyrocarbonate reactivity. This is confirmed by diethyl pyrocarbonate footprinting of the complex between antibodies to Z-DNA and the AC-rich region. Osmium tetroxide and hydroxylamine reveal some distortions of the Z double helix in the (GT/CA)n stretch also. The terminal T residues of the stretch are hyperreactive with osmium tetroxide; the terminal left C residues but not the terminal right C residues are hyperreactive with hydroxylamine. Substitution of a few base pairs in the middle of the (GT/CA)n stretch induces also some distortions of the Z double helix. In the GT/CA-rich sequence, distortion of the Z double helix is also supported by the hyperreactivity of osmium tetroxide with several T and C residues.

Animals↗