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Biomedical subjects

S Meyer

Publications and source records attributed to S Meyer.

At least 91 records · Page 5Linked to original sources

AtSUC3, a gene encoding a new Arabidopsis sucrose transporter, is expressed in cells adjacent to the vascular tissue and in a carpel cell layer.

The cDNA corresponding to the open reading frame T17M13.3 from Arabidopsis chromosome II was isolated and the encoded protein was characterized as a member of a subgroup of higher plant sucrose transporters. The AtSUC3 (Arabidopsis thaliana sucrose transporter 3) open reading frame encodes a protein with 594 amino acid residues, being 81 and 82 residues longer than the previously described Arabidopsis sucrose carriers AtSUC1 and AtSUC2. About 50 of these additional amino acids are part of an extended cytoplasmic loop separating the N-terminal from the C-terminal half of the protein. For functional characterization the AtSUC3 cDNA was expressed in baker's yeast. Substrate specificities, energy dependence and K(m) values of the recombinant protein were determined. Removal of the enlarged cytoplasmic loop and expression of the truncated cDNA caused no detectable change in the kinetic properties of the protein, suggesting a transport-independent function for this cytoplasmic domain. Immunolocalization with an AtSUC3-specific antiserum identified the protein in a cell layer separating the phloem from the mesophyll and in a single, subepidermal cell layer of the carpels that is important for pod dehiscence. These localizations suggest a possible role of AtSUC3 in the funnelling of sucrose from the mesophyll towards the phloem, and possibly in pod shatter.

Amino Acid Sequence↗

[Methods for quality assurance of medical examination in epidemiological field studies: the "Study of Health in Pomerania" (SHIP)].

The aims of the population-based, cross-sectional survey "Study of Health in Pomerania" (SHIP) are to describe prevalences and distributions of a broad range of diseases, as well as environmental and behavioural risk factors in the region of Pomerania (North-eastern Germany). The examinations are performed in two study units by different physicians, technicians and interviewers and laboratory analyses in two separate laboratories. In addition, the study will take at least 3 years and approximately 7000 persons will be examined. Because of the design of the study a special concept of quality assurance is indispensable. In the present paper methods are presented for quality assurance and control in anthropometry, ECG, echocardiography, abdominal sonography, carotid ultrasound, sonography of the thyroid gland, blood pressure measurements as well as clinical laboratory analyses. The technical control protocols, the training programmes of the observers and methods to establish observer and method variabilities are presented by means of typical examples. The logistic, personal and technical measures for quality assurance and control require appropriate attention. The methods and procedures presented here are expected to provide an effective instrument to continually monitor the quality of medical examinations in the SHIP study.

Adult↗

Birth trauma: short and long term effects of forceps delivery compared with spontaneous delivery on various pelvic floor parameters.

OBJECTIVE: To compare the effects of forceps delivery and spontaneous delivery on pelvic floor functions in nulliparous women. DESIGN: A longitudinal prospective study with investigations during the first pregnancy, 10 weeks and 10 months after delivery. SETTING: Antenatal clinic in a teaching hospital. POPULATION: One hundred and seven patients aged 28 +/- 4 years, divided into those with forceps (n = 25) or spontaneous (n = 82) delivery. METHODS: Investigations with a questionnaire, clinical examination, assessment of bladder neck behaviour, urethral sphincter function, intra-vaginal/intra-anal pressures during pelvic floor contractions. RESULTS: The incidence of stress urinary incontinence was similar in both groups at 9 weeks (32% vs 21%, P = 0.3) and 10 months (20% vs 15%, P = 0.6) after delivery, as was the incidence of faecal incontinence (9 weeks: 8% vs 4%, P = 0.9; 10 months: 4% vs 5%, P = 1) and the decreased sexual response at 10 months (12% vs 18%, P = 0.6). Bladder neck behaviour, urethral sphincter function and intra-vaginal and intra-anal pressures were also similar in the two groups. However, 10 months after delivery, the incidence of a weak pelvic floor (20% vs 6%, P = 0.05) and the decrease in intra-anal pressure between the pre- and post-delivery values (-17 +/- 28 cm H2O vs 3 +/- 31 cm H2O, P = 0.04) were significantly greater in the forceps-delivered women. CONCLUSIONS: Forceps delivery is not responsible for a higher incidence of pelvic floor complaints or greater changes in bladder neck behaviour or urethral sphincter functions. However, patients with forceps delivery have a significantly greater decrease in intra-anal pressure and a greater incidence of a weak pelvic floor.

Adult↗

Communal orientation may not buffer burnout.

Communal orientation (a desire to give and receive benefits in response to the needs of and out of concern for others) has had a buffer effect on burnout, in particular when the helping relationship is perceived by the helper as inequitable. This result, however, comes from research involving a specific professional group, medical personnel, that is, a group with a medical helping model wherein recipients are neither held responsible for their problem nor for the solution. We hypothesized that among professional helpers with a compensatory model wherein recipients are not held responsible for their problem but for the solution, and who perceive the relationship as inequitable, not only will a communal orientation not have effect on burnout, but it will reduce personal accomplishment. We present some results supporting this hypothesis.

Adult↗

[Quantitative risk assessment related to microbial food contamination] [In Process Citation]

The four keystones of quantitative risk assessment are hazard identification, exposure assessment, dose-response assessment and risk characterization. This paper considers the different steps of risk assessment and their application to food microbiology. Traditionally, quantitative risk assessment has been viewed simply as a method to estimate risk. However, when we conduct a complete risk assessment including different factors from "farm to fork" it can serve to understand the risk process. Quantitative risk assessment can also provide valuable insights as how to best manage the risk.

Journal Article↗

Metabolism of vitamin A and its active metabolite all-trans-retinoic acid in small intestinal enterocytes.

Retinol and its metabolites (retinoids) are essential for growth and cell differentiation, particularly of epithelial tissue. Retinoids mediate most of their function via interaction with retinoid receptors (retinoic acid receptors and retinoid X receptors), which act as ligand-activated transcription factors controlling the expression of a number of target genes. We have investigated whether retinoid receptor ligands such as all-trans-retinoic acid (RA) are formed in the human intestinal epithelium from dietary vitamin A. We show here that retinol was metabolized to its active metabolite, all-trans-RA, by isolated cytosolic fractions of human small intestinal enterocytes and by human Caco-2 cells. All-trans-RA was metabolized by human small intestinal microsomes to at least two metabolites (all-trans-4-hydroxy-RA and all-trans-4-oxo-RA). When Caco-2 cells were incubated with all-trans-RA, at least three major polar metabolites (all-trans-4-hydroxy-RA, all-trans-4-oxo-RA, and 13-cis-4-hydroxy-RA) were identified by HPLC-UV. The cytochrome P450 (CYP) 1A1 inhibitor alpha-naphthoflavone inhibited the metabolism of all-trans-RA, whereas the CYP1A1 inducer beta-naphthoflavone induced the metabolism of all-trans-RA, suggesting that CYP1A1 is involved. The induction of CYP3A by rifampicin enhanced the metabolism, and the induction of all-trans-RA metabolism was also observed after preincubation of the cells with all-trans-RA. Liarozole almost completely inhibited the RA metabolism. The specific retinoic acid metabolizing CYP26 was induced after RA treatment in Caco-2 cells. It is concluded that in addition to CYP1A1 and CYP3A, CYP26 may be the main CYP enzyme responsible for the metabolism of all-trans-RA in enterocytes. Active ligands such as all-trans-RA are formed in intestinal epithelial cells.

Caco-2 Cells↗

[Quantitative risk assessment related to microbial food contamination].

The four keystones of quantitative risk assessment are hazard identification, exposure assessment, dose-response assessment and risk characterization. This paper considers the different steps of risk assessment and their application to food microbiology. Traditionally, quantitative risk assessment has been viewed simply as a method to estimate risk. However, when we conduct a complete risk assessment including different factors from "farm to fork" it can serve to understand the risk process. Quantitative risk assessment can also provide valuable insights as how to best manage the risk.

Animals↗

Studies of vehicular padding materials.

The Federal Motor Vehicle Safety Standard 571.201 discusses occupant protection with interior impacts of vehicles. Rule making by the National Highway Traffic Safety Administration (NHTSA) has identified padding for potential injury reduction in vehicles. In these studies, head injury mitigation with padding on vehicular roll bars and brush bars was evaluated. Studies were conducted with free falling Hybrid 50% male head form drops on the forehead and side of the head and a 5% female head. Marked reductions in angular acceleration, as well as Head Injury Criterions (HIC), were observed when compared to unpadded roll bars and brush bars.

Acceleration↗

Optimized analysis of intracellular adenosine and guanosine phosphates in Escherichia coli.

To investigate the intracellular concentrations of adenosine phosphates in Escherichia coli, especially during bioreactor cultivations, a method that enables reproducible determination of adenosine phosphates in culture solutions containing at least 0.25 g dry cell weight/L has been developed. The detection limits of AMP, ADP, and ATP were found to be as low as 1 pmol. The method involves fast sampling, instantaneous inactivation of cell metabolism, extraction of nucleotides, and quantitative analysis by ion-pair reversed-phase HPLC.

Adenine Nucleotides↗

Extended lymph-node dissection for gastric cancer.

BACKGROUND: Curative resection is the treatment of choice for gastric cancer, but it is unclear whether this operation should include an extended (D2) lymph-node dissection, as recommended by the Japanese medical community, or a limited (D1) dissection. We conducted a randomized trial in 80 Dutch hospitals in which we compared D1 with D2 lymph-node dissection for gastric cancer in terms of morbidity, postoperative mortality, long-term survival, and cumulative risk of relapse after surgery. METHODS: Between August 1989 and July 1993, a total of 996 patients entered the study. Of these patients, 711 (380 in the D1 group and 331 in the D2 group) underwent the randomly assigned treatment with curative intent, and 285 received palliative treatment. The procedures for quality control included instruction and supervision in the operating room and monitoring of the pathological results. RESULTS: Patients in the D2 group had a significantly higher rate of complications than did those in the D1 group (43 percent vs. 25 percent, P<0.001), more postoperative deaths (10 percent vs. 4 percent, P= 0.004), and longer hospital stays (median, 16 vs. 14 days; P<0.001). Five-year survival rates were similar in the two groups: 45 percent for the D1 group and 47 percent for the D2 group (95 percent confidence interval for the difference, -9.6 percent to +5.6 percent). The patients who had R0 resections (i.e., who had no microscopical evidence of remaining disease), excluding those who died postoperatively, had cumulative risks of relapse at five years of 43 percent with D1 dissection and 37 percent with D2 dissection (95 percent confidence interval for the difference, -2.4 percent to +14.4 percent). CONCLUSIONS: Our results in Dutch patients do not support the routine use of D2 lymph-node dissection in patients with gastric cancer.

Aged↗

Inflammatory cytokines and vascular endothelial growth factor stimulate the release of soluble tie receptor from human endothelial cells via metalloprotease activation.

Activation of endothelial cells, important in processes such as angiogenesis, is regulated by cell surface receptors, including those in the tyrosine kinase (RTK) family. Receptor activity, in turn, can be modulated by phosphorylation, turnover, or proteolytic release of a soluble extracellular domain. Previously, we demonstrated that release of soluble tie-1 receptor from endothelial cells by phorbol myristate acetate (PMA) is mediated through protein kinase C and a Ca2+-dependent protease. In this study, the release of soluble tie-1 was shown to be stimulated by inflammatory cytokines and vascular endothelial growth factor (VEGF), but not by growth factors such as basic fibroblast growth factor (bFGF) or transforming growth factor alpha (TGFalpha). Release of soluble tie by tumor necrosis factor alpha (TNFalpha) or VEGF occurred within 10 minutes of stimulation and reached maximal levels within 60 minutes. Specificity was shown by fluorescence-activated cell sorting (FACS) analysis; endothelial cells exhibited a significant decrease in cell surface tie-1 expression in response to TNF, whereas expression of epidermal growth factor receptor (EGF-R) and CD31 was stable. In contrast, tie-1 expression on megakaryoblastic UT-7 cells was unaffected by PMA or TNFalpha. Sequence analysis of the cleaved receptor indicated that tie-1 was proteolyzed at the E749/S750 peptide bond in the proximal transmembrane domain. Moreover, the hydroxamic acid derivative BB-24 demonstrated dose-dependent inhibition of cytokine-, PMA-, and VEGF-stimulated shedding, suggesting that the tie-1 protease was a metalloprotease. Protease activity in a tie-1 peptide cleavage assay was (1) associated with endothelial cell membranes, (2) specifically activated in TNFalpha-treated cells, and (3) inhibited by BB-24. Additionally, proliferation of endothelial cells in response to VEGF, but not bFGF, was inhibited by BB-24, suggesting that the release of soluble tie-1 receptor plays a role in VEGF-mediated proliferation. This study demonstrated that the release of soluble tie-1 from endothelial cells is stimulated by inflammatory cytokines and VEGF through the activation of an endothelial membrane-associated metalloprotease.

Amino Acid Sequence↗

HvrBase: compilation of mtDNA control region sequences from primates.

HvrBase is a compilation of human and ape mtDNA control region sequences. Sequences and related information on individuals, such as from where the sequences were obtained, is stored in three ASCII files as described previously. Moreover, the collection is also available as Mac/PC database application with a graphical user interface. It can be accessed through the WWW at URL http://www.eva.mpg.de/hvrbase. The current collection comprises 5846 human sequences from hypervariable region I (HVRI) and 2302 human sequences from hypervariable region II (HVRII). From apes, 295 HVRI sequences and 13 HVRII sequences are available.

Animals↗

[Microsurgical reanastomosis of the parotid duct].

Deep injuries to the parotid region may result in trauma to vital structures: i.e., the parotid gland and duct and the facial nerve and its branches. While there is no doubt concerning primary microsurgical reconstruction of injuries to the facial nerve clinical approaches for treating disruptions of the parotid duct have been controversial. A case report is presented of a secondarily reanastomosed parotid duct following complete transection. The microsurgical technique and its indications are discussed.

Anastomosis, Surgical↗

Heterogeneous inhibition of photosynthesis over the leaf surface of rosa rubiginosa L. during water stress and abscisic acid treatment: induction of a metabolic component by limitation of CO(2) diffusion

The contribution of changes in stomatal conductance and metabolism in determining heterogeneous photosynthesis inhibition during dehydration and abscisic acid (ABA) feeding was investigated using detached leaves of Rosa rubiginosa L. The steady-state and maximal rates of electron transport under a transient high CO(2) concentration were monitored using chlorophyll fluorescence imaging. The decrease in electron transport rate induced by dehydration and ABA treatment almost reverted to the control rate under transient high CO(2) availability. Therefore, inhibition of photosynthesis was mainly mediated through stomatal closure. However, since reversion was not complete, a metabolic inhibition was also identified as a decrease in the maximal electron transport rate driven by carboxylation. Under dehydration or ABA feeding, as under low ambient CO(2) treatment, in 21% or 0.4% O(2), the lower the steady-state electron transport was, the lower was the maximal electron transport rate during transient high CO(2) availability. We conclude that low CO(2) availability reduced the capacity of ribulose-1,5-bisphosphate carboxylase-oxygenase (Rubisco) to drive electron transport. The potential contribution of Rubisco deactivation mediated by stomatal closure is discussed.

Journal Article↗

Pattern of nucleotide substitution and rate heterogeneity in the hypervariable regions I and II of human mtDNA.

This study provides a comprehensive survey of the complex pattern of nucleotide substitution in the control region of human mtDNA, which is of central importance to the studies of human evolution. A total of 1229 different hypervariable region I (HVRI) and 385 different hypervariable region II (HVRII) sequences were analyzed using a complex substitution model. Moreover, we suggest a new method to assign relative rates to each site in the sequence. Estimates are based on maximum-likelihood methods applied to randomly selected subsets of sequences. Our results indicate that the rate of substitution in HVRI is approximately twice as high as in HVRII and that this difference is mainly due to a higher frequency of pyrimidine transitions in HVRI. However, rate heterogeneity is more pronounced in HVRII.

DNA, Mitochondrial↗

Prolonged neoadjuvant chemotherapy with GM-CSF in locally advanced breast cancer.

BACKGROUND: Neoadjuvant chemotherapy improves survival in patients with locally advanced breast cancer (LABC). Usually three to four cycles of conventional-dose neoadjuvant chemotherapy are administered prior to local therapy, and another three cycles thereafter. In an attempt to improve results, we increased the dosages and applied GM-CSF, which, besides being a hematopoietic growth factor, has become increasingly known for its immunostimulatory effects, which might enhance the antitumor effect. METHODS: Forty-two patients with stage IIIA or IIIB breast cancer were treated with doxorubicin (A) (90 mg/m2) and cyclophosphamide (C) (1,000 mg/m2) at three-weekly intervals. In the second and fourth cycle a 10% dose reduction of both agents was applied. On the second day GM-CSF 250 micrograms/m2/day was started and given for 10 days. Initially, some patients were treated with < or = four cycles, but as the study progressed and toxicity appeared tolerable, six cycles were given whenever possible. After the chemotherapy, patients underwent surgery and postoperative radiotherapy. RESULTS: The response rate for the whole group to AC was 98% (95% confidence interval 94%-100%), with a clinical complete response rate of 50% (95% confidence interval 35%-65%). Six patients had a pathological complete response. Median follow-up from the start of chemotherapy is 49 months (range 10-100). The disease-free survival (DFS) at three years is 57% and the overall survival (OS) at three years is 79%. There is a significant trend for improved DFS (p = 0.0000) and OS (p = 0.0002) with increasing number of cycles. CONCLUSION: The results of the present study with neoadjuvant dose-intensive AC chemotherapy and GM-CSF compare favorably with previous studies in patients with LABC. This is most apparent in patients who received six cycles of neoadjuvant chemotherapy. We hypothesize that these encouraging results are probably related to the prolonged presence of the primary tumor, and to the long-term administration of GM-CSF with the primary tumor and axillary lymph nodes in situ. Therefore, a randomized study is warranted. We already initiated an international randomized trial in patients with LABC in order to answer two questions. First, does prolonged neoadjuvant chemotherapy result in an improved DFS and OS in comparison with the conventional approach, and secondly, what is the effect of GM-CSF in this approach in comparison with G-CSF?

Adult↗

Amplification of ColE1 related plasmids in recombinant cultures of Escherichia coli after IPTG induction.

ColE1-derived plasmids containing different recombinant genes which are controlled by the tac promoter were amplified following induction with IPTG, but no amplification occurred if product formation was not induced. The plasmid copy number of recombinant E. coli increased three- to sixfold within a period of about 6 h in shake flask experiments, batch cultures, and glucose-limited fed-batch cultivations. Plasmid amplification occurred in E. coli B strains as well as in K-12 strains with different plasmids (rop+ and rop-) coding for various heterologous proteins. The amplification was not caused by a toxic effect of IPTG, but was related to a strong inhibition of translation and chromosomal replication after the induction of heterologous gene expression. Similar to the amplification after chloramphenicol addition, plasmid replication proceeded even if oriC replication and translation were inhibited following strong induction of a recombinant gene. In accordance with the effect of chloramphenicol, the level of ppGpp, which is a negative regulator of ColE1 derived plasmid replication, decreased after induction.

Bacterial Proteins↗