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Biomedical subjects

K Meyer

Publications and source records attributed to K Meyer.

At least 91 records · Page 5Linked to original sources

Use of an acute spinal cord injury clinical pathway.

Phased outcome clinical pathways can be useful in the management of neurotrauma patients in the acute care setting. By developing multidisciplinary plans of care that focus on patient and family outcomes and not arbitrary points in time, hospitals can provide quality care to trauma patients that is both appropriate and cost effective. In fact, this type of plan for SCIs can be expanded on and used across the health care continuum from prehospital to community reintegration. Providing collaborative quality care will result in improved outcomes for both patients and health care institutions.

Acute Disease↗

Hemodynamic responses during leg press exercise in patients with chronic congestive heart failure.

To increase muscle mass and strength in patients with chronic congestive heart failure (CHF), there is a need for implementing resistance exercises in exercise training programs. This study sought to assess the safety of rhythmic strength exercise with respect to left ventricular function in 9 patients with stable CHF, compared with 6 stable coronary patients with mild left ventricular dysfunction (control group). With use of right-sided catheterization, changes in left ventricular function were assessed during double leg press exercise at loads of 60% and 80% of maximum voluntary contraction. The exercise sessions lasted 14 minutes each, divided into work and recovery phases of 60/120 seconds. In CHF, during exercise at a 60% load, there was a significant increase in heart rate (mean +/- SEM 90 +/- 4 beats/min; p <0.05), mean arterial blood pressure (95 +/- 3 mm Hg; p <0.01), diastolic pulmonary artery pressure (20.2 +/- 2.7 mm Hg; p <0.01), and cardiac index (3 +/- 0.3 L/m2/min; p <0.05). Additionally, during leg press exercise at an 80% load, there was a significant decrease in systemic vascular resistance (1,086 +/- 80 dynes x s x cm(-5); p <0.001), an increased cardiac index (3.4 +/- 0.1; p <0.001), and left ventricular stroke work index (75 +/- 5 g x m/m2; p <0.01), suggesting enhanced left ventricular function. Compared with controls, in CHF the magnitude of changes in hemodynamic parameters during exercise, demonstrated at a 60% load, was significantly smaller (systemic vascular resistance: [mean] 1,613 --> 1000 vs 1472 --> 1,247 dynes x s x cm(-5); cardiac index: 2.4 --> 3 vs 2.8 --> 4.4 L/m2/min, and stroke work index: 60 --> 69 vs 114 --> 155 g x m/m2; p <0.05 each). Nevertheless, changes indicated an enhanced contractile function of the left ventricle in CHF. This study demonstrates stability of left ventricular function during resistance exercise in well-compensated CHF patients with optimal drug therapy, as well as the appropriateness of the chosen mode and intensity applied as these factors relate to cardiovascular stress. This conclusion cannot be extrapolated to patients with less well-compensated heart failure, or to more protracted resistance training.

Exercise↗

Dietary flavonoid intake and risk of cardiovascular disease in postmenopausal women.

Flavonoids, a group of phenolic compounds found in fruits and vegetables, are known to have antioxidant properties. They prevent low density lipoprotein oxidation in vitro and thus may play a role in the prevention of coronary heart disease (CHD). In 1986, in a prospective study of 34,492 postmenopausal women in Iowa, the authors examined the association of flavonoid intake with CHD and stroke mortality. Over 10 years of follow-up, 438 deaths from CHD and 131 deaths from stroke were documented. Total flavonoid intake was associated with a decreased risk of CHD death after adjusting for age and energy intake (p for trend = 0.04). This association was attenuated after multivariate adjustment. However, decreased risk was seen in each category of intake compared with the lowest. Relative risks and 95% confidence intervals of CHD death from lowest to highest intake category were 1.0, 0.67 (95% confidence interval (CI) 0.49-0.92), 0.56 (95% CI 0.39-0.79), 0.86 (95% CI 0.63-1.18), and 0.62 (95% CI 0.44-0.87). There was no association between total flavonoid intake and stroke mortality (p for trend = 0.83). Of the foods that contributed the most to flavonoid intake in this cohort, only broccoli was strongly associated with reduced risk of CHD death. The data of this study suggest that flavonoid intake may reduce risk of death from CHD in postmenopausal women.

Aged↗

Allelic variants of dopamine receptor D4 (DRD4) and serotonin receptor 5HT2c (HTR2c) and temperament factors: replication tests.

The contribution of genetic factors to personality differences between individuals is evidenced by twin and adoption studies. Ebstein et al. [1996, 1997a, 1997b] reported an association between the long repeat allele of the dopamine D4-exon-III receptor polymorphism and the human personality dimension novelty seeking (NS), between the 5HT2c-ser-23 allele and reward dependence, and an interaction between both receptor polymorphisms and reward dependence. Subsequent replication tests mainly reported controversial results for the association between DRD4-exon-III long repeat and NS. We examined a homogeneous study population of 190 healthy male students of middle European descent, aged between 20 and 30 years using Cloninger's TPQ in order to replicate Ebstein's findings. Using a significance level of 1%, no association between the long repeat of the DRD4-exon-III polymorphism and NS and between the 5HT2c receptor polymorphism and reward dependence was found, but a significant interaction effect of DRD4 and 5HT2c receptor polymorphisms on reward dependence was observed in accordance to Ebstein's report.

Adult↗

A leucine-rich repeat protein of carrot that exhibits antifreeze activity.

A gene encoding an antifreeze protein (AFP) was isolated from carrot (Daucus carota) using sequence information derived from the purified protein. The carrot AFP is highly similar to the polygalacturonase inhibitor protein (PGIP) family of apoplastic plant leucine-rich repeat (LRR) proteins. Expression of the AFP gene is rapidly induced by low temperatures. Furthermore, expression of the AFP gene in transgenic Arabidopsis thaliana plants leads to an accumulation of antifreeze activity. Our findings suggest that a new type of plant antifreeze protein has recently evolved from PGIPs.

Amino Acid Sequence↗

Species differences in induction of hepatic enzymes by BM 17.0744, an activator of peroxisome proliferator-activated receptor alpha (PPARalpha).

BM 17.0744, a new anti-diabetic and lipid-lowering agent, leads also to strong hepatomegaly and carnitine acetyl transferase (CAT) increase in the liver of rats, a phenomenon known from fibrates. For information on the relevance of changes in liver of rats to other species, we investigated the effects of BM 17.0744 on lipids and selected marker enzymes related to beta-oxidation in rats, dogs and guinea-pigs, so-called high and low responders to peroxisome proliferators. To examine selectivity other enzymes were also determined, e.g. esterase, urate oxidase (UOX) and cytochrome c oxidase (CYT.C.OX.). Lowering of triglycerides and cholesterol in blood serum and/or liver was observed in pharmacological dose range in the three species tested. In dogs and guinea-pigs, liver and kidney weights were unaffected even in dogs in medium and high dose groups with high systemic exposure and severe toxicity. In male Sprague-Dawley rats treatment with 1.5, 3, 6 and 12.5 mg/kg per day BM 17.0744 selectively elevated the activities of CAT and acyl-CoA oxidase (AOX) by < or =200 and 20-fold, respectively. Administration of BM 17.0744 to Beagle dogs (1.5, 4, 12 mg/kg per day) and guinea-pigs (3 and 12 mg/kg per day) enhanced the activities of CAT and AOX dose-dependently by a factor of two to three only. Immunoblotting revealed a drug-specific enhancement of the amount of beta-oxidation enzymes in rats, which is in accord with the rapid and coordinated transcriptional activation shown in Northern dot blot analysis. Nuclear run-on assays demonstrated a real transcriptional activation. BM 17.0744 activates peroxisome proliferator-activated receptor alpha (PPARalpha), which could be shown by transactivation assays. The stimulation of PPARalpha by BM 17.0744 was stronger than that of the known ligands WY 14.643 and ETYA. Activation of PPARgamma can be excluded. Taken collectively, the data demonstrate an enhancement of the beta-oxidation system by BM 17.0744 paralleled by lipid-lowering in all species investigated. The activation of the nuclear factor PPARalpha may explain the changes in liver and the metabolic effects on the molecular level. The lack of an increase in liver and kidney weights and the relatively moderate enhancement of activities of beta-oxidation-related enzymes in dogs and guinea-pigs indicate that the excessive response observed in rats is not applicable to other, predominantly non-rodent, species. On the basis of these data and the experience with fibrates a specific risk for humans is not expected.

Animals↗

Independent diagnostic value of fluorescein angiography in the evaluation of intraocular tumors.

BACKGROUND: Fluorescein angiography has been used in the clinical evaluation of suspected neoplastic lesions of the ocular fundus for over 30 years. Yet, the independent diagnostic value of this photographic technique in patients with suspected intraocular neoplasms has never been determined. METHODS: The authors evaluated color fundus photographs and fluorescein angiograms of 50 mass lesions of the ocular fundus. The cases were chosen to reflect a broad spectrum of lesions, including choroidal malignant melanoma, choroidal nevus, circumscribed choroidal hemangioma, metastatic carcinoma to the choroid, miscellaneous other neoplasms, hamartomas, or choristomas, and non-neoplastic lesions simulating neoplasms. Ten experienced retinal specialists independently reviewed the angiograms (presented in random order without the corresponding color fundus photographs) and rendered a diagnosis. Approximately 1 month later, each retinal specialist independently reviewed the color fundus slides (presented in a different random order without the corresponding fluorescein angiograms) and again rendered a diagnosis for each lesion. RESULTS: The accuracy of angiographic diagnosis by the different reviewers ranged from 16% to 56% (average 45.4%), while that based on review of the color fundus slides ranged from 32% to 78% (average 59.0%). This difference is statistically significant. CONCLUSION: Fluorescein angiography alone did not appear to be a reliable method for establishing the clinical diagnosis of neoplasms and simulating lesions of the ocular fundus.

Carcinoma↗

Functional analysis of a transrepressor domain in the hepatitis C virus core protein.

Hepatitis C virus (HCV) is one of the major causative agents of chronic liver disease with the potential for development of hepatocellular carcinoma. The putative core protein of the virus has many intriguing properties, including transcriptional regulation of cellular and unrelated viral promoters. To further characterize the transregulatory function, a number of chimeric constructs were made by fusion of the core gene to the DNA binding domain of the yeast transactivator factor GAL4. The fusion protein exhibited a repressor activity on the herpes simplex virus thymidine kinase promoter via the upstream GAL4 DNA binding sites. A structure /function analysis of HCV core mutants in the context of the GAL4 DNA binding domain revealed that the transcriptional repressor activity was located near the N-terminus (amino acids 26 85). Transcription was strongly inhibited upon transfer of this repressor domain to a heterologous activation domain, (3CGln) of Epstein Barr virus transcription factor EBNA3C. Results from this study suggest that the HCV core protein contains an overall repressor activity, and that the repressor domain is located near the N-terminus.

3T3 Cells↗

Role of P-selectin expression in hepatic ischemia and reperfusion injury.

BACKGROUND: Researchers have shown that reperfusion of ischemic tissues initiates a complex series of reactions that paradoxically injure tissues. Although several mechanisms have been proposed to explain the pathobiology of ischemic/reperfusion (I/R) injury, much attention has focused on adhesion molecules. Our research is intended to show the kinetics of P-selectin in the liver in response to I/R injury. METHODS: Left-lobar hepatic ischemia was induced for 30 min in 35 C57BL-6 mice and 20 P-selectin-deficient (K-O) mice. P-selectin expression was measured in these mice at 20 min, 2, 5, 12 and 24 h reperfusion times, as well as in control and sham animals. The animals were injected with radio-labeled P-selectin monoclonal antibody and the organs were harvested for counts/g tissue, expressed as the percentage injected dose. Serum liver enzymes were measured and pathological sections of ischemic and control livers were performed. The unpaired t-test was used for statistical analysis. RESULTS: P-selectin expression showed two peaks in this animal model. The first peak was at 20 min and the second peak at 5 h of reperfusion (p < 0.001). We documented an 8-fold increase in aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) levels 10 h following I/R injury. Pathological specimens showed periportal necrosis consistent with an ischemic event. P-selectin K-O mice showed no up-regulation as a separate control group, and the liver enzymes were significantly lower than the wild-type mice at 10 h (p < 0.001). CONCLUSION: P-selectin has a bimodal expression following hepatic I/R injury. The first peak is attributed to the Weibel-Palade bodies and the second to new translational P-selectin. We noted no difference in the up-regulation of P-selectin in the ischemic and non-ischemic liver lobes in the same animal.

Alanine Transaminase↗

Detection of melengestrol acetate residues in plasma and edible tissues of heifers.

The aim of this study was to gain knowledge of residue formation after the use of melengestrol acetate (MGA) as a growth-promoting agent. Two Holstein-Friesian heifers each received a daily dose through the feed of 0, 0.5 mg (2 heifers with and without withdrawal each), 1.5 mg or 5.0 mg MGA for 8 weeks. MGA residues in plasma were screened by enzyme immuno-assay (EIA). Concentrations in kidney, liver, and muscle were quantified by liquid-chromatography-mass spectrometry (LC-MS), and in fat by gas chromatography-mass spectrometry (GC-MS). MGA levels in plasma were 40, 128, and 280 ng/L, respectively. Residues accumulated in muscle and kidney (5-fold), liver (20-to-40-fold), and fat (200-fold). After administration of 1.5 mg per day the mean MGA concentration in fat was 29 micrograms/kg and thus violated USA regulations which specify a limit of 25 ppb. Therefore the labelled use of MGA (0.5 mg per day) has to be officially controlled.

Adipose Tissue↗

Left ventricular function during interval and steady state exercise.

PURPOSE: Interval training (INT) is a commonly used method of exercise training in both athletic and clinical populations. Although we generally understand left ventricular (LV) function during steady state (SS) exercise, there are no data regarding LV function during INT. METHODS: We studied eight healthy, physically active volunteers during upright cycle ergometry during 15 min of both SS and INT, at the same average power output (90% individual anaerobic threshold), using first pass radionuclide ventriculography. During INT (60s/60s), measures of LV function were made during work (220 W) after 4 and 12 min and during recovery (120 W) after 7 and 15 min. These were compared with the average of four temporally matched measures made during SS (170 W). RESULTS: During INT, LV ejection fraction increased from rest (67 +/- 6%) to 77 +/- 5, 80 +/- 5, 77 +/- 5 and 79 +/- 4% after 4, 7, 12, and 15 min, respectively. During SS, LV ejection fraction was not significantly different at rest (70 +/- 4%) or during exercise (76 +/- 4, 79 +/- 4, 80 +/- 3, and 81 +/- 3%) after 4, 7, 12, and 15 min, respectively. Other measures of LV function (HR, BP, LV volumes, cardiac output, systemic vascular resistance, peak emptying, and filling rates) were likewise similar during temporally matched measurements during INT and SS. CONCLUSIONS: Although there were the expected transitions of ejection fraction with work and recovery, the overall hemodynamic picture during INT was very similar to SS. These data suggest that LV function during INT is not substantially different to that during SS.

Aged↗

Hepatitis C virus NS5A protein modulates cell cycle regulatory genes and promotes cell growth.

The phosphoprotein NS5A of hepatitis C virus has recently been suggested to control PKR protein kinase for resistance to interferon. To investigate other functions of NS5A, studies were initiated on the regulation of transcription of important cellular genes and of cell growth by this protein. The results suggested that NS5A protein represses transcription of the cell cycle regulatory gene p21WAF1, while it activates the human proliferating cell nuclear antigen gene in murine fibroblasts and human hepatoma cells. Furthermore, introduction of NS5A into murine fibroblasts (NIH3T3) promoted anchorage-independent growth and tumour formation in nude mice. Thus, NS5A appears to exhibit a role in cell growth regulation.

Animals↗

Regulation of ferulate-5-hydroxylase expression in Arabidopsis in the context of sinapate ester biosynthesis.

Sinapic acid is an intermediate in syringyl lignin biosynthesis in angiosperms, and in some taxa serves as a precursor for soluble secondary metabolites. The biosynthesis and accumulation of the sinapate esters sinapoylglucose, sinapoylmalate, and sinapoylcholine are developmentally regulated in Arabidopsis and other members of the Brassicaceae. The FAH1 locus of Arabidopsis encodes the enzyme ferulate-5-hydroxylase (F5H), which catalyzes the rate-limiting step in syringyl lignin biosynthesis and is required for the production of sinapate esters. Here we show that F5H expression parallels sinapate ester accumulation in developing siliques and seedlings, but is not rate limiting for their biosynthesis. RNA gel-blot analysis indicated that the tissue-specific and developmentally regulated expression of F5H mRNA is distinct from that of other phenylpropanoid genes. Efforts to identify constructs capable of complementing the sinapate ester-deficient phenotype of fah1 mutants demonstrated that F5H expression in leaves is dependent on sequences 3' of the F5H coding region. In contrast, the positive regulatory function of the downstream region is not required for F5H transcript or sinapoylcholine accumulation in embryos.

Alleles↗

Interaction of eukaryotic initiation factor eIF4B with the internal ribosome entry site of foot-and-mouth disease virus is independent of the polypyrimidine tract-binding protein.

Eukaryotic translation initiation factor 4B (eIF4B) binds directly to the internal ribosome entry site (IRES) of foot-and-mouth disease virus (FMDV). Mutations in all three subdomains of the IRES stem-loop 4 reduce binding of eIF4B and translation efficiency in parallel, indicating that eIF4B is functionally involved in FMDV translation initiation. In reticulocyte lysate devoid of polypyrimidine tract-binding protein (PTB), eIF4B still bound well to the wild-type IRES, even after removal of the major PTB-binding site. In conclusion, the interaction of eIF4B with the FMDV IRES is essential for IRES function but independent of PTB.

Aphthovirus↗

Leptin and leptin receptor expression in a lipoblastoma in an 8-year-old girl.

Leptin is a hormone that is produced by adipocytes. Leptin acts on specific receptors in the hypothalamus. RNA was isolated from a lipoblastoma of an 8-year-old girl and the expression of leptin and leptin receptor mRNA was analyzed by RT-PCR. The lipoblastoma tumor, a rare form of childhood tumors, expressed leptin and leptin receptors in a fashion similar to normal adipose tissue. We hypothesize that the peripheral action of leptin via its receptors could play a role in the development and/or progression of lipoblastoma. Whether or not leptin and leptin receptor expression play a role in the development and/or progression of lipoblastoma and other tumors is not clear to date. Copyrightz1999S.KargerAG, Basel

Adipocytes↗

A role for leptin in sexual maturation and puberty?

Leptin, the ob gene product, is involved in the regulation of body weight in rodents, primates and humans. It provides a molecular basis for the lipostatic theory of the regulation of energy balance. White adipose tissue and placenta are the main sites of leptin synthesis. There is also evidence of ob gene expression in brown fat. Leptin seems to play a key role in the control of body fat stores by coordinated regulation of feeding behaviour, metabolic rate, autonomic nervous system regulation and body energy balance. Apart from the function of leptin in the central nervous system on the regulation of energy balance, it may well be one of the hormonal factors that signal to the brain the body's readiness for sexual maturation and reproduction. During late pregnancy and at birth when maternal fat stores have been developed, leptin levels are high. During these developmental stages leptin could be a messenger molecule signalling the adequacy of the fat stores for reproduction and maintenance of pregnancy. At later stages of gestation leptin could signal the expansion of fat stores in order to prepare the expectant mother for the energy requirements of full-term gestation, labour and lactation. Leptin serum concentrations change during pubertal development in rodents, primates and humans. In girls, leptin serum concentrations increase dramatically as pubertal development proceeds. The pubertal rise in leptin levels parallels the increase in body fat mass. In contrast, leptin levels increase shortly before and during the early stages of puberty in boys and decline thereafter. Testosterone has been found to suppress leptin synthesis by adipocytes both in vivo and in vitro. The decline of leptin levels in late puberty in boys accompanies increased androgen production during that time and most likely reflects suppression of leptin by testosterone and a decrease in fat mass and relative increase in muscle mass during late puberty in males. This overview focuses on those topics of leptin research which are of particular interest in reproductive and adolescent medicine.

Animals↗