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Biomedical subjects

K Meyer

Publications and source records attributed to K Meyer.

At least 199 records · Page 11Linked to original sources

Biosynthesis of ferulic acid esters of plant cell wall polysaccharides in endomembranes from parsley cells.

A microsomal preparation from suspension-cultured parsley cells is able to transfer ferulic acid from the respective CoA thioester to endogenous acceptors. The reaction is not enhanced by digitonin but stimulated by Mg2+, Ca2+ and Co2+. Spermine can partly replace divalent ions. Solubility properties and degradation by polysaccharide hydrolases suggest that the products are polymeric cell wall carbohydrates. Sucrose density gradient centrifugation revealed that the most active vesicle fraction is distinct from plasma membranes but does also not peak with IDPase. It is suggested that a subfraction of the Golgi-apparatus is the source of enzyme and acceptors.

Acyl Coenzyme A↗

Mixed model analysis of a selection experiment for food intake in mice.

Data from 23 generations of mice selected for increased and reduced appetite were analysed by Restricted Maximum Likelihood fitting an animal model with litters as additional random effects. Traits considered were food intake between 4 and 6 weeks of age adjusted for 4-week body weight (AFI), the selection criterion, and body weight at 6 weeks (6WW). Selection was carried out within families. A high and a low selection line and a control were maintained in each of three replicates. Analyses were performed for each replicate separately taking subsets of the data spanning different numbers of generations. Overall estimates of heritabilities were 0.15 for AFI, which agreed well with realized heritability estimates, and 0.42 for 6WW. The litter variance, expressed as a proportion of the phenotypic variance, was 0.21 for both traits, yielding intraclass correlations of full-sibs of 0.29 and 0.42, respectively. Similar results were obtained for variances of each trait using univariate and multivariate analyses. From the latter, estimates of correlations between the two traits were 0.46 for additive genetic, -0.19 for litter and 0.31 for residual effects, resulting in a phenotypic correlation of 0.23. Analyses of data from generations 2-7, 8-13 and 14-23 separately showed a marked decrease in genetic variance and heritability in later generations for both traits. Heritabilities of AFI, for instance, were 0.24, 0.10 and 0.07, respectively. These changes could not be attributed to the effects of inbreeding or of selection in an infinitesimal model and suggested that some change in variance due to change in gene frequency had occurred during the course of the experiment.

Analysis of Variance↗

Regulation of ovarian steroid biosynthesis by estrogen during proestrus in the rat.

Studies were performed to test the hypothesis that the rapid decline in estradiol (E2) levels on proestrus before ovulation was due to a reduction in androgen substrate for aromatase, and that this decline in androgen was regulated by an estrogen receptor-mediated mechanism. Aromatase activity, concentrations of E2, androstenedione (A), testosterone (T), and progesterone (P4) in follicular, corpora lutea, and ovarian homogenates as well as peripheral E2, A, P4, and LH were measured in cycling rats from 1400-2000 h on proestrus. These parameters were also recorded after the expected E2 surge in animals treated at 1900 h on diestrous day 2 with the antiestrogen keoxifene (20 mg/kg), with or without an ovulatory dose of PMSG at 1600 h on proestrus. In a second experiment, P-450-17 alpha-hydroxylase/C17,20-lyase (P-450(17 alpha] activity was measured in a group of control rats at 1500, 1700, and 1900 h. Aromatase activity remained unchanged, even though serum and ovarian E2 levels were reduced from peak values at 1500 h to basal values at 1800 h (P less than 0.01). Peripheral A as well as ovarian androgens (specifically follicular but not luteal) A and T were also reduced over this time period (P less than 0.01). Although total ovarian P4 remained unchanged, follicular levels rose from 1400-2000 h (P less than 0.01). These reductions in androgens and E2 levels coincided with a marked reduction in follicular P-450(17 alpha) activity. Treatment with keoxifene with or without PMSG prevented the fall in peripheral E2 and A and the increase in peripheral P4 seen in controls. Ovarian and follicular E2, A, and to a lesser extent T were also remained at values similar to those during the E2 surge. Follicular P4 was reduced by both treatments. Neither treatment had any effect on aromatase. These results indicate that the fall in peripheral and ovarian E2 levels before ovulation was due to a decline in aromatizable androgen, through an inhibition of follicular P-450(17 alpha) enzyme activity, which appears to be mediated by an estrogen receptor-regulated mechanism.

Analysis of Variance↗

Heterogeneity of expression and secretion of native and mutant [AspB10]insulin in AtT20 cells.

AtT20 (pituitary corticotroph) cells were transfected with either the native or a mutant [AspB10]rat insulin II gene, using a plasmid containing the insulin gene and a neomycin resistance gene under the control of independent constitutive promoters. The cellular immunoreactive insulin (IRI) content ranged from 0.8-440 ng/10(6) cells, with the highest value similar to that found for a rat insulinoma cell line (RIN) and corresponding to approximately 1% that of native pancreatic B-cells. There was a direct correlation between insulin mRNA levels and IRI content and no correlation between mRNA levels and rat insulin II gene copy number. Furthermore, in some lines the insulin II transgene was lost even though the gene encoding neomycin resistance was retained. IRI release was stimulated up to 4-fold by isobutylmethylxanthine in all lines transfected with the native rat insulin II gene, and HPLC analysis showed most IRI as fully processed insulin, with less than 5% as proinsulin. These cells, thus, directed most proinsulin to secretory granules for conversion and regulated release regardless of the absolute amount of IRI expressed. One of the lines transfected with the AspB10 mutant gene (line AA9) released nearly 50% of IRI as proinsulin under basal conditions, with stimulation of insulin, but not proinsulin, release by isobutylmethylxanthine. This confirmed our previous finding of partial diversion of this mutant proinsulin from the regulated to the constitutive pathway. A second line (IC6) expressing the same mutant gene at much higher levels appeared to direct all mutant proinsulin to the regulated pathway, suggesting that for this particular mutant proinsulin, the secretory pathway employed by the transfected cells can be affected by the amount of proinsulin synthesized.

Animals↗

Estimates of covariances between reproduction and growth in Australian beef cattle.

Estimates of covariance components between scrotal circumference, serving capacity, days to calving, and yearling and final weight were obtained for Hereford, Angus, and Zebu cross cattle in temperate and tropical Australia. Analyses were carried out by REML employing a derivative-free algorithm and fitting bivariate animal models. Aspects of modeling and computational requirements related to the use of this method are discussed. Estimates of heritabilities agreed closely with those from univariate analyses, being low for female reproductive performance and moderate to high for male reproduction and growth. Estimates of genetic correlation between male and female fertility traits were low but favorable, being -.25, -.28, and -.41 between scrotal circumference and days to calving for Herefords, Angus, and Zebu crosses, respectively. Genetic correlations between male reproductive traits and weights ranged from .24 to .52 for the temperate breeds and were higher (.65 to .69) for Zebu crosses. Phenotypic correlations between scrotal circumference and weights were similar for all breeds, ranging from .32 to .47, whereas serving capacity and weights were phenotypically unrelated. Estimates of correlations between days to calving and weights were less consistent. Phenotypically, there was little association between the two traits. Genetic correlations for Zebu crosses were negative and low to moderate (-.36 to -.66) and estimates for Angus were close to zero.

Analysis of Variance↗

[Can the training of coronary patients be monitored by readily measurable parameters?].

The prognosis of coronary patients in terms of the mortality of coronary heart disease shows a positive relation to the severity of clinical and functional diagnostic parameters. Thus exercise therapy should be monitored by criteria that take ischemia, the myocardial situation and rhythm disorders into account. These criteria should be reliable and should be easy to determine as well as to apply. For pragmatic reasons the non-invasive evaluation of findings and the diagnostic symptom-limited ergometer test are especially significant for dosage and monitoring of exercise therapy. Monitored exercise therapy is here understood to mean individually adjusted exercising by patients, and training thus has to be based on diagnostic findings. First existing complaints have to be analyzed and such findings as size of infarction in the ECG, heart volume in the X-ray, size and function of the left ventricle by echography, etc. checked. Afterwards maximum physical work capacity on a multistage bicycle ergometer test is measured with respect to the following termination criteria: a) subjective reports by the patient during exercise (e.g. onset and severity of angina pectoris, dyspnea and/or fatigue of the leg muscles) and b) objective criteria such as significant ischemic ST-depression, exercise-hypertension, age-related submaximal heart rate and significant rhythm disorders. An inverse correlation is found between measured maximum symptom-limited physical performance and the frequency of cardiac termination criteria; a comparable inverse correlation exists with heart volume: max. O2 pulse.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Disease↗

Tumor factors predicting for prognosis in metastatic breast cancer. The presence of P24 predicts for response to treatment and duration of survival.

Fifty-one patients with metastatic breast cancer were investigated to determine tumor parameters with prognostic significance. Investigations included determinations of P24 content by immunocytochemical means using a monoclonal antibody to P24 protein; immunocytochemical analysis of estrogen and progesterone receptors; ploidy analysis by flow cytometry, and histologic grading. There were significant correlations between the presence of P24 and estrogen receptor, between histologic grade and P24 expression, and between estrogen and progesterone receptors. Of the tumor factors investigated only P24 protein was, however, of prognostic significance. Patients with P24-positive tumors had a significantly higher rate of response to treatment as well as more prolonged duration of response and duration of survival from diagnosis of metastatic disease. None of the other variables investigated were significantly predictive of outcome. P24 protein may be a useful predictor of prognosis in metastatic breast cancer.

Antibodies, Monoclonal↗

Effect of alpha-interferon, 17 beta-estradiol, and tamoxifen on estrogen receptor concentration and cell cycle kinetics of MCF 7 cells.

The interaction of alpha-interferon, 17 beta-estradiol, and tamoxifen on estrogen receptor content, growth fraction, proliferative rate, and total protein synthesis of MCF 7 cells was investigated under culture conditions (minus phenol red and at low concentrations of "stripped" fetal calf serum) allowing for direct stimulation of proliferation by estrogens. Exposure to estradiol alone resulted in a decrease of estrogen receptor content as measured by immunoassay, an increase of the proportion of cells in S phase, and increases in cell proliferation as well as total protein synthesis. alpha-Interferon treatment resulted in cell cycle arrest with reduced proliferation, an increase of estrogen receptor content, but a decrease in the rate of total protein synthesis. Pretreatment with alpha-interferon inhibited the estrogen induced stimulation of cell growth as well as the associated decrease of estrogen receptor content. Tamoxifen treatment resulted in decreased cell proliferation and decrease of estrogen receptor content and of total protein synthesis. These results suggest that the estrogen receptor concentration of MCF 7 cells is growth fraction related. Pretreatment with alpha-interferon enhanced the inhibitory effect of tamoxifen on cell proliferation while preventing the tamoxifen induced reduction of estrogen receptor content. The synergistic effect of alpha-interferon and tamoxifen are most marked following 72 h pretreatment with interferon, when the maximum interferon induced increase of estrogen receptor concentration is evident. The mechanism is thus due probably to an increase of cellular receptor as a ligand for tamoxifen binding and suggests a possible role for the clinical use of interferons combined with tamoxifen.

Breast Neoplasms↗

Response to second-line hormone treatment for advanced breast cancer. Predictive value of ploidy determination.

Twenty-two patients who previously responded to first-line hormonal therapy were evaluated for factors which would predict for response to second hormonal manipulation. Investigations performed at progression after initial hormone response included immunocytochemical estimation of estrogen and progesterone receptors as well as flow cytometric analysis of tumor ploidy. Approximately 50% of patients were found still to be estrogen receptor positive at relapse from first-line hormone treatment. Progesterone receptor had, however, usually become negative. Nine of the 22 patients responded to second-line hormonal therapy. Second hormone responses occurred with equal frequency among hormone receptor-positive and hormone receptor-negative patients. Tumor ploidy, as determined by flow cytometric study did, however, predict for response. Eight of 12 patients with diploid tumors responded to second-line hormone therapy whereas only one of ten with aneuploid tumors responded. Flow cytometric analysis appears to be a promising technique for prediction of second hormone response after relapse from first-line hormone manipulation.

Aminoglutethimide↗

Interval versus continuous exercise training after coronary bypass surgery: a comparison of training-induced acute reactions with respect to the effectiveness of the exercise methods.

In order to improve endurance by exercise on a bicycle ergometer, both the interval method (I) (exertion and recovery phases alternate each minute) and the continuous method (constant exertion) can be employed. We examined the effects of both methods on the following parameters: heart rate, blood pressure, rate-pressure product, glucose, lactate, and catecholamine levels, and physical performance. Two groups of nine male patients were trained daily on a bicycle ergometer for 3.5 weeks. These patients had undergone coronary bypass surgery 24 and/or 26 days before the training started. The training heart rate was set at 86% of the individual maximum heart rate. In the last week of training, the exercise intensity in both patient groups, following either I or C regimen, was 20:121 W and 83 W respectively. The exercise training lasted 20 minutes with the following findings: (1) there were no significant differences in blood pressure, rate-pressure product, rates of glucose and catecholamines, and (2) there was a significantly higher rate of lactate in the second ten minutes of the I training. Before and after the training period, the patients were subjected to a multistage bicycle ergometer exercise test (sitting). The following results obtained after the training favor the I method: (1) patients' physical performance increased (+0.63 vs. +0.26 W/kg; p less than 0.001); (2) heart rate was lower at rest (-9 vs. -4 beats/min; p less than 0.04) and at 75 W (-12 vs. -2 beats/min; p less than 0.02); (3) rate-pressure product was lower at rest (-1675 vs. -291; p less than 0.04) and at 75 W (-2810 vs. -735; p less than 0.05); (4) rate of lactate was lower at 75 W (-0.83 vs. -0.33 mmol/l; p less than 0.04); (5) catecholamines were not lowered by I or C training, and no differences between the two groups could be observed. Exercise training according to the I method involves both the aerobic and anaerobic capacity of the organism, whereas exercise training according to the C method involves only oxidative capacity. After coronary bypass surgery, the I method is better suited to increase physical performance and is more effective in economizing the cardiac function.

Adult↗

Pleomorphic adenomas with unbalanced chromosomal abnormalities have an increased in vitro lifetime.

The in vitro lifetime of 100 salivary gland pleomorphic adenomas was investigated. On the average, they had a limited lifetime of 3.7 passages. In 86 cases, the tumors were successfully karyotyped, resulting in three major cytogenetic subgroups characterized by either an apparently normal karyotype or by rearrangements of 8q12 or 12q13-15. There was no significant difference between the in vitro lifetime of the tumors with a normal or with an aberrant karyotype. The three adenomas with the longest lifetime were characterized by an unbalanced karyotype. One of them had a deleted chromosome 6, which has also been described in malignant tumors. An increased in vitro lifetime may thus correspond to early steps of malignant transformation in vivo and can be caused by additional unbalanced chromosome aberrations. In the future, long-term cultivation can be helpful in defining chromosomal regions involved in this process.

Adenoma↗

Detection of P24 protein in human breast cancer: influence of receptor status and oestrogen exposure.

The expression of oestrogen regulated protein, P24, was investigated in 69 breast cancers. At initial evaluation P24 protein was detected significantly more frequently and was present in significantly higher concentration in oestrogen receptor positive than in receptor negative tumours. There was, however, no correlation between P24 staining and progesterone receptor, tumour ploidy or proliferative index. Nineteen patients received a short course of treatment with diethylstilboestrol. Following treatment with oestrogen, P24 staining became positive in 7/13 tumours previously negative for P24, including six tumours which were oestrogen receptor negative. Oestrogen administration also caused an increase of the proliferation index in 12/19 tumours, including 5/7 that were oestrogen receptor positive and 7/12 that were oestrogen receptor negative. In some instances oestrogenic stimulation of proliferation occurred together with increased P24 expression; in other instances proliferation index increased without induction of P24 synthesis. The in vivo effects of oestrogen in clinical breast cancer thus appear to show dissociation between enhancement of protein synthesis and cellular proliferation.

Breast Neoplasms↗

Estimation of PR and ER by immunocytochemistry in breast cancer. Comparison with radioligand binding methods.

Immunocytochemical assays for progesterone receptor (PR) using monoclonal antirabbit PR antibodies (PR-ICA) and for estrogen receptor (ER) (ER-ICA) were compared with radioligand binding (dextran-coated charcoal [DCC]) methods for receptor determination in patients with breast cancer. Immunocytochemical staining for PR was exclusively nuclear in localization. In this regard, PR staining is similar to previous findings for ER; PR-ICA showed a sensitivity of 89% and specificity of 100%. ER-ICA was also 89% sensitive and similarly specific. There was good correlation between the degree and intensity of staining and quantitative binding of radioligand. Receptor-positive tumors, however, show considerable variation of immunocytochemical staining, suggesting heterogeneity of cellular PR content. The availability of an immunocytochemical assay for PR increases the discriminatory potential for these methods of receptor determination.

Adult↗

[Acute cardiovascular and metabolic changes in interval and endurance training in selected patients following aortocoronary bypass operation].

UNLABELLED: This study compared the acute changes of cardiovascular and metabolic reactions during interval and continuous training after coronary bypass surgery. Two groups of 9 male patients (age: 59 +/- 4 and 56 +/- 6 years, resp.) each trained on bicycle ergometer start on post-operative days 24 and 26, resp. In both training groups training heart rate was set at 86% of individual maximum heart rate. In the last week of training the exercise intensity in the group of patients who were trained by the continuous method was at 83 watts, and at 20:121 watts in the group of patients who were trained by interval method (rest:work each 1:1 min). At this exercise training that lasted for 20 min the acute response of heart rate, blood pressure, rate-pressure product, glucose, lactate and catecholamines was measured. RESULTS: In both methods there were no significant differences in systolic and diastolic pressure, rate-pressure product, in glucose or catecholamine levels. However, there was a significantly higher rate of lactate in the second 10 min of the interval training. And, in spite of higher peripheral exercise intensity by interval training, there was no higher cardiac work than by the continuous training. These findings suggest that interval training strains the oxidative capacity of the trained muscles in a more intensive and direct way than does continuous training.

Adult↗

[Effects of interval versus endurance training of increasing performance, cardiovascular function, metabolism and catecholamines in selected patients after aortocoronary bypass operation].

This paper reports the effect of endurance exercise training on bicycle ergometer by interval method (work and interval each 1:1 min) and continuous method on increase of physical performance, decrease of heart rate, rate-pressure-product, glucose, lactate, and catecholamines. Two groups of nine male patients (aged 59 +/- 4 vs 56 +/- 6 (mean +/- SD)) after coronary bypass surgery each participated in the inpatient rehabilitation training. Training started 24 and 26 days, resp., after surgery and lasted for 3.5 weeks. Frequency and duration of exercise training: Monday-Friday 1 x 20 min and 1 x 25 min per day; Saturday/Sunday each 1 x 25 min per day. In the interval group and the continuous group the exercise training intensity was set at 86% of individual max. heart rate. In the last week of training mean exercise intensity was at 83 watts in the group of patients who were trained by the continuous method and at 20:121 watts in the group of patients who were trained by the interval method. Before and after the training period patients underwent a multistage bicycle ergometer exercise test in sitting position. Beginning at 25 w, each stage was increased by 25 w, whereby each stage lasted 3 min. Cutoff criteria were heart rate (220 - age x 0.85) and/or fatigue of the leg muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of treatment with aromatase inhibitor 4-hydroxandrostenedione on the nonhuman primate menstrual cycle.

4-Hydroxyandrostenedione (4-OHA) is a potent inhibitor of rat ovarian and human placental aromatase activity as assessed in vitro and has been shown to suppress ovarian estrogen secretion in vivo in rats. The compound inhibited extragonadal aromatization in male rhesus monkeys and reduced plasma levels of estradiol in postmenopausal women with advanced, metastatic breast cancer. Furthermore, 4-OHA caused disease remission in these patients. Prior to using this compound in premenopausal patients, the present study was carried out to determine whether 4-OHA affects the menstrual cycle by inhibiting ovarian estrogen production in nonhuman primate species. Four baboons (Papio anabis) exhibiting regular menstrual cycles were studied. Blood samples were collected daily throughout a control menstrual cycle and during treatment with daily s.c. injections of 4-OHA. Menstruation was not observed in three of four animals during treatment and did not resume until cessation of 4-OHA administration. The midcycle surge of estradiol which averaged 411 pg/ml in the control menstrual cycle was reduced during 4-OHA treatment by a mean of 49% of control. Thereafter, with continued 4-OHA treatment, serum concentrations of estradiol were significantly reduced below the basal control level [75.3 +/- 5.6 (SE) pg/ml] and were very low or undetectable. Perineal turgescence, an index of estrogenicity, was inhibited by 4-OHA administration. The preovulatory surge of serum luteinizing hormone, which averaged 114 ng/ml during the control cycle, appeared normal in three of four animals following 12 to 14 days of 4-OHA administration, but no luteinizing hormone surge occurred with continued 4-OHA administration. The results indicate that, although 4-OHA reduces ovarian estrogen formation during the first cycle, treatment for a second consecutive cycle appears to be necessary for maximal suppression.

Androstenedione↗