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Biomedical subjects

A Winter

Publications and source records attributed to A Winter.

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

Pharmacokinetics of gallic acid and its relative bioavailability from tea in healthy humans.

Gallic acid (GA), a food component that is especially abundant in tea, is an antimutagenic, anticarcinogenic and anti-inflammatory agent. We conducted a study using acidum gallicum tablets that contained 10% GA and 90% glucose and a black tea brew that contained 93% of its GA in free form to determine the pharmacokinetics and relative bioavailability of GA in healthy humans. After the administration of a single oral dose of acidum gallicum tablets or tea (each containing 0.3 mmol GA) to 10 volunteers, plasma and urine samples were collected over various time intervals. Concentrations of GA and its metabolite, 4-O-methylgallic acid (4OMGA), were determined, and the pharmacokinetic parameters were calculated. GA from both the tablets and tea was rapidly absorbed and eliminated with mean half-lives of 1.19 +/- 0.07 and 1.06 +/- 0.06 h and mean maximum concentrations of 1.83 +/- 0.16 and 2.09 +/- 0.22 micromol/L (plasma), respectively. After oral administration of the tablets and black tea, 36.4 +/- 4.5 and 39.6 +/- 5.1% of the GA dose were extracted in urine as GA and 4OMGA, respectively. The relative bioavailability of GA from tea compared with that from the tablets was 1.06 +/- 0.26, showing that GA is as available from drinking tea as it is from swallowing tablets of GA.

Adult↗
PubMed2001

A UML-based ontology for describing hospital information system architectures.

To control the heterogeneity inherent to hospital information systems the information management needs appropriate hospital information systems modeling methods or techniques. This paper shows that, for several reasons, available modeling approaches are not able to answer relevant questions of information management. To overcome this major deficiency we offer an UML-based ontology for describing hospital information systems architectures. This ontology views at three layers: the domain layer, the logical tool layer, and the physical tool layer, and defines the relevant components. The relations between these components, especially between components of different layers make the answering of our information management questions possible.

Hospital Information Systems↗
PubMed2000

Quantitative expression analysis of the cellular specificity of HECT-domain ubiquitin E3 ligases.

We evaluated the expression of 28 gene sequences with homology to the carboxy terminal of HECT E3 ubiquitin ligases in nine human cell lines using RT-PCR, to determine whether gene expression could be associated with cell-specific functions (HECT is "homologous to E6AP C-terminus"). In general, HECT-domain E3 ligases are constitutively expressed at low levels with a broad range between cell types. hecth3, 21, and 23 had higher levels in three leukocytic lines (Jurkat, MM6, THP1); hecth11 was more abundant in HepG2 and A495; and hecth15 and hecth12 were differentially expressed in lung fibroblasts derived from normal and severe emphysema patients (CCD16 and CCD29, respectively). Absolute quantitation showed that most HECT E3s have about 20-100 copies of mRNA per Jurkat cell. By comparison, UBCH7 (an ubiquitin-conjugating E2) is 10-fold more abundant in Jurkat cells and 30-fold more abundant than E2 UBCH5A. We interpret the broad range of transcript levels to be consistent with the hypothesis that the concentrations of E3 are important for ubiquitination selectivity, leading us to conclude that substrate activation is necessary but not sufficient for selectivity.

Amino Acid Sequence↗
PubMed2000

Targeted inhibition of transcription elongation in cells mediated by triplex-forming oligonucleotides.

Triple-helix-forming oligonucleotides (TFOs) bind in the major groove of double-stranded DNA at oligopyrimidine small middle dotoligopurine sequences and therefore are candidate molecules for artificial gene regulation, in vitro and in vivo. We recently have described oligonucleotide analogues containing N3'-P5' phosphoramidate (np) linkages that exhibited efficient inhibition of transcription elongation in vitro. In the present work we provide conclusive evidence that np-modified TFOs targeted to the HIV-1 polypurine tract (PPT) sequence can inhibit transcriptional elongation in cells, either in transient or stable expression systems. The same constructs were used in transient expression assays (target sequence on transfected plasmid) and in the generation of stable cell lines (target sequence integrated into cellular chromosomes). In both cases the only distinguishable feature between the cellular systems is the presence of an insert containing the wild-type PPT/HIV-1 sequence, a mutated version with two mismatches, or the absence of the insert altogether. The inhibitory action induced by np-TFOs was restricted to the cellular systems containing the complementary wild-type PPT/HIV-1 target, and consequently can be attributed only to a triple-helix-mediated mechanism. As a part of this study we also have applied an imaging technique to quantitatively investigate the dynamics of TFO-mediated specific gene silencing in single cells.

Animals↗
PubMed2000

Emergency coronary artery bypass grafting after failed coronary angioplasty: what has changed in a decade?

BACKGROUND: We assessed the impact of patient and procedural characteristics on the outcome after emergency coronary artery bypass grafting (CABG) for failed percutaneous transluminal coronary angioplasty (PTCA) and temporal changes in these factors. METHODS: Patients who underwent PTCA and subsequent emergency CABG were identified from the databases of the Departments of Cardiology and Cardiothoracic Surgery. RESULTS: Two periods of clinical practice were compared. In 1989 to 1993, 2,880 PTCAs were performed, 64 patients underwent emergency CABG (2.3%), and 7 patients died (10.9%). During 1994 to 1998, 46 patients of 3,801 PTCAs underwent emergency CABG (1.2%, p < 0.01), and 7 patients died (15.2%, NS). The average rate of stenting increased from 0.8% to 24% in 1994 to 1998 as well as the frequency of arterial bypass grafts (0% vs 39%). In the latter period, patients were older, were more often females, had more cardiovascular risk factors, a higher Cleveland score (each p < 0.05), and suffered more often from periprocedural myocardial infarctions (p < 0.001) and nonfatal periprocedural complications (p < 0.01). CONCLUSIONS: Although the frequency of emergency CABG after failed PTCA declined, perioperative mortality tended to increase according to an unfavorable shift in patient risk factors and morbidity.

Adult↗
PubMed2000

Decision support in medicine: a survey of problems of user acceptance.

Computer-based clinical decision support systems (CDSSs) are still today not in widespread use, although there has been extensive research and development for several decades. We have, based on the literature of the last years, summarised some of the problems that may lead to low user acceptance and that should be addressed more extensive in future developments of CDSSs. We describe different aspects of the usefulness of CDSSs according to the elements (relevance, validity, and work) of a formula of usefulness of information, and, in a short section, refer to the discussion about clinical guidelines.

Attitude of Health Personnel↗
PubMed2000

Purpose and structure of strategic plans for information management in hospitals.

Information management in hospitals requires a strategic plan that gives directives for the construction and development of a hospital information system. The paper describes the purpose and a suggested structure for those strategic plans. This structure is a central component for a guideline that may be used for creating and updating strategic plans.

Germany↗
PubMed1999

Vaccination with the plasminogen activator from Streptococcus uberis induces an inhibitory response and protects against experimental infection in the dairy cow.

Two antigens comprising either concentrated culture filtrate containing the plasminogen activator, PauA (total antigen) or the same preparation from which PauA had been selectively removed by incubation with a PauA-specific monoclonal antibody and immobilisation on Protein-G agarose (depleted antigen) were combined with either Freund's incomplete adjuvant (FIA) or a commercially used adjuvant (SB62) and used to vaccinate dairy cows by a subcutaneous route. Immunisation of four animals with depleted antigen combined with FIA conferred no protection to mastitis following intramammary challenge with S. uberis 0140J. However, immunisation of two groups of four animals with the total antigen combined with either FIA or SB62 induced protection in 3 out of 8 and 5 out of 8 similarly challenged quarters, respectively. Protection corresponded to the production of an inhibitory antibody response to PauA.

Animals↗
PubMed1999

Early autonomic dysfunction in patients with diabetes mellitus assessed by spectral analysis of heart rate and blood pressure variability.

Patients with diabetes mellitus (DM) often have alterations of the autonomic nervous system (ANS), even early in their disease course. Previous research has not evaluated whether these changes may have consequences on adaptation mechanisms in DM, e.g. to mental stress. We therefore evaluated whether patients with DM who already had early alterations of the ANS reacted with an abnormal regulatory pattern to mental stress. We used the spectral analysis technique, known to be valuable and reliable in the investigation of disturbances of the ANS. We investigated 34 patients with DM without clinical evidence of ANS dysfunction (e.g. orthostatic hypotension) and 44 normal control subjects (NC group). No patients on medication known to alter ANS responses were accepted. The investigation consisted of a resting state evaluation and a mental stress task (BonnDet). In basal values, only the 21 patients with type 2 DM were different in respect to body mass index and systolic blood pressure. In the study parameters we found significantly lower values in resting and mental stress spectral power of mid-frequency band (known to represent predominantly sympathetic influences) and of high-frequency and respiration bands (known to represent parasympathetic influences) in patients with DM (types 1 and 2) compared with NC group (5.3 +/- 1.2 ms2 vs. 6.1 +/- 1.3 ms2, and 5.5 +/- 1.6 ms2 vs. 6.2 +/- 1.5 ms2, and 4.6 +/- 1.7 ms2 vs. 6.2 +/- 1.5 ms2, for resting values respectively; 4.7 +/- 1.4 ms2 vs. 5.9 +/- 1.2 ms2, and 4.6 +/- 1.9 ms2 vs. 5.6 +/- 1.7 ms2, and 3.7 +/- 2.1 ms2 vs. 5.6 +/- 1.7 ms2, for stress values respectively; M/F ratio 6/26 vs. 30/14). These differences remained significant even when controlled for age, sex, and body weight. However, patients with DM type 2 (and significantly higher body weight) showed only significant values in mental stress modulus values. There were no specific group effects in the patients with DM in adaptation mechanisms to mental stress compared with the NC group. These findings demonstrate that power spectral examinations at rest are sufficiently reliable to diagnose early alterations in ANS in patients with DM. The spectral analysis technique is sensitive and reliable in investigation of ANS in patients with DM without clinically symptomatic autonomic dysfunction.

Adult↗
PubMed1999

NCAM, vimentin and neonatal myosin heavy chain expression in human muscle diseases.

The intermediate filament protein vimentin, the neonatal isoform of the myosin heavy chain gene (MHCn), and the neural cell adhesion molecule (NCAM) are developmentally and/or neurally regulated molecules that reappear transiently after the induction of necrosis, or denervation. Immunostaining using antibodies against these molecules helps to identify regenerating and/or denervated muscle fibres even if they are not recognized by conventional staining procedures. This study examined the expression of vimentin, MHCn, and NCAM using immunohistochemistry in 82 biopsy specimens from muscular dystrophies, inflammatory myopathies, and neurogenic atrophies. Anti-vimentin labelled significantly more fibres than anti-MHCn staining in the inflammatory myopathies (P<0.03) but not in the muscular dystrophies (P=0.58) and neurogenic atrophies (P=0. 58). The fraction of NCAM+ fibres was always more elevated than vimentin+ or MHCn+ fibres. In the necrotizing myopathies, most NCAM+ fibres were regenerating ones (co-expressing vimentin). In neurogenic atrophies, half the NCAM+ fibres were regenerating and half of them were NCAM+/vimentin- and thus were considered to be denervated. Taken together, anti-vimentin staining detects a broader spectrum of regenerating fibres than anti-MHCn, at least in the inflammatory myopathies. The number of anti-NCAM labelled fibres in the necrotizing myopathies is similar, but not identical, to the number of regenerating fibres. Co-staining with anti-vimentin (or anti-MHCn) and anti-NCAM identifies a subset of fibres that is considered to be denervated.

Adolescent↗
PubMed1998

Heterogeneity of mutant versus wild-type Ki-ras in primary and metastatic colorectal carcinomas, and association of codon-12 valine with early mortality.

The point mutations occurring in codons 12 and 13 of Ki-ras in 78 patients with colorectal carcinoma (31 Dukes' A and B, 21 Dukes' C, and 26 Dukes' D) have been determined by allele-specific oligonucleotide hybridization and sequencing. Duplicate samples of invasive primary carcinoma, adjacent normal tissue, and available lymph node and liver metastases from the same patients were microdissected from paraffin sections. There were no differences in the mutation rate between primary carcinomas and secondary deposits: 26 of 78 (33 per cent) primary carcinomas, 10 of 32 (31 per cent) lymph node metastases, and 10 of 26 (38 per cent) liver metastases. Multiple sampling revealed frequent heterogeneity within carcinomas: 9 of 26 primaries with Ki-ras mutations also contained areas of carcinoma with only the wild-type gene, implying that Ki-ras mutation, even when present in a colonic carcinoma, may not have been necessary for establishing the malignant phenotype. Also, 2 of 26 (8 per cent) Dukes' D patients had a mutation in their primary carcinoma but none in liver metastases and 6 of 47 (13 per cent) Dukes' C and D patients had mutations in liver or lymph node metastases but none in the primary carcinoma. Such heterogeneity may modify the effectiveness of novel therapies targeting mutant Ki-ras function, such as farnesyltransferase inhibition. Mutation of codon 12 from GGT (glycine) to GTT (valine) was more prevalent in primary and metastatic deposits of Dukes' C/D carcinomas (P = 0.01) than in primary carcinomas from Dukes' A/B patients. Mutations of codon 12 to GAT, AGT, GCT and codon 13 GGC to GAC were also found, but no correlation with carcinoma aggressiveness was apparent. Follow-up of 71/78 patients (up to 12 years) revealed decreased overall survival (P = 0.001) in patients with the GGT to GTT transversion in codon 12, even when the analysis was restricted to Dukes' D cases, supporting the suggestion that this mutation may confer a more aggressive phenotype in colorectal carcinoma.

Adenocarcinoma↗
PubMed1998

Effects of ketorolac and dextran-70 alone and in combination on haemostasis.

BACKGROUND: Dextran may be used in surgical patients for thromboprophylaxis or volume expansion along with ketorolac, a nonsteroidal anti-inflammatory drug, for analgesia. As these two agents can influence the haemostatic system at different sites, it is important to demonstrate that there is no adverse haemostatic interaction between them. METHODS: The haemostatic interaction between intravenous dextran-70 and intramuscular ketorolac was assessed in a double-blind, randomised, crossover study of healthy male volunteers each given all four combinations of ketorolac/placebo intramuscularly and dextran/placebo intravenously. The effect of ketorolac and dextran on haemostasis was assessed by the following techniques: skin bleeding time, in vitro platelet aggregation function, whole blood thromboxane generation, von Willebrand factor antigen, factor VIII coagulant activity and tissue plasminogen activator. The results were analysed for the effects of ketorolac and dextran and for any evidence of an interaction. RESULTS: Ketorolac inhibited platelet function and thromboxane generation. Dextran reduced factor VIII coagulant activity. Neither agent had a significant effect on bleeding time, von Willebrand factor or tissue plasminogen activator. There was only evidence of a small but statistically significant interaction between ketorolac and dextran on thromboxane generation. There was no evidence of any other interaction of ketorolac with dextran. CONCLUSION: This interaction on thromboxane generation is unlikely to be of clinical significance as substantial inhibition of thromboxane generation occurs with ketorolac alone.

Adult↗
PubMed1997

Differential metabolism of dynorphins in substantia nigra, striatum, and hippocampus.

To map the proteolytic enzymes metabolizing dynorphins in brain structures, size-exclusion chromatography linked to electrospray ionization mass spectrometry was used. Enzymes extracted from rat hippocampus, striatum, and substantia nigra were tested for their capability of converting dynorphin-related peptides. Dynorphin A was the most resistant to proteolytic conversion, whereas Big dynorphin and dynorphin B-29 were slowly converted to dynorphin A and dynorphins A and B, respectively. Dynorphin B and alpha-neoendorphin were the least resistant. Dynorphin B was rapidly converted to Leu-enkephalin in the striatum and hippocampus but to Leu-enkephalin-Arg6 in the substantia nigra. alpha-Neoendorphin was converted to Leu-enkephalin in all tissues investigated.

Amino Acid Sequence↗
PubMed1997

Further studies on the efficacy of a live vaccine against mastitis caused by Streptococcus uberis.

Three groups of dairy cows were immunized by subcutaneous (s.c.) administration of a preparation of live Streptococcus uberis (strain 0140J) and an intramammary infusion of a soluble surface extract derived from same the bacteria. Animals in Groups 1 and 2 received two s.c. vaccinations plus an intramammary inoculation. Animals in Group 3 received two s.c. vaccinations but did not receive the intramammary infusion. In addition to the vaccinated animals, each group also contained two non-vaccinated (control) animals. All animals were challenged experimentally by intramammary infusion (in two quarters per animal) of ca 100 c.f.u. of S. uberis (strain 0140J or C221) and monitored for clinical signs of disease, bacterial numbers in milk, somatic cell count in milk, and daily milk yield for the following 10 days. Animals in Group I were challenged with strain 0140J. Only one out of six challenged quarters of three vaccinated cows developed clinical disease compared to all (four out of four) quarters of non-vaccinated cows. Animals in Group 2 were challenged with strain C221. All challenged quarters of three vaccinated (six out of six) and two non-vaccinated (four out of four) cows developed clinical mastitis. Animals in Group 3 were challenged with strain 0140J. Five out of eight quarters on four vaccinated cows developed clinical mastitis but the onset was delayed in comparison with that in both non-vaccinated cows in which four out of four challenged quarters developed clinical mastitis. These results indicated that vaccination with live S. uberis protects against challenge with the homologous strain but was less effective against a heterologous strain. Reduced protection was also seen when the intramammary booster was omitted.

Animals↗