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Biomedical subjects

D Mayer

Publications and source records attributed to D Mayer.

At least 55 records · Page 3Linked to original sources
PubMed1999

Insulin receptor substrate-1 is over-expressed in glycogenotic but not in amphophilic preneoplastic hepatic foci induced in rats by N-nitrosomorpholine and dehydroepiandrosterone.

Insulin receptor substrate-1 (IRS-1) is over-expressed in preneoplastic glycogenotic hepatic foci (GSF) and is gradually down-regulated during progression of these lesions, via mixed cell foci (MCF), to the basophilic neoplastic phenotype. The aim of the present study was to investigate the effect of dehydroepiandrosterone (DHEA), a weak hepatocarcinogen and tumour enhancer, on IRS-1 expression. Hepatocellular lesions were induced by N-nitrosomorpholine followed by DHEA. Under these conditions, many glycogen-poor amphophilic (APF) and intermediate cell foci (ICF) appear, in addition to GSF and MCF. IRS-1 was over-expressed in 215 out of 295 GSF, in 50 out of 53 MCF and in a glycogen-rich mixed cell adenoma. IRS-1 expression was not shown in 147 APF, 51 ICF and 5 amphophilic hepatocellular adenomas, and 3 out of 5 hepatocellular carcinomas showed a weak IRS-1 expression. The results suggest a close association of IRS-1 over-expression with the glycogenotic hepatocellular phenotype. The modulation and enhancement of tumour progression by DHEA is associated with a shift from glycogenosis to amphophilia and basophilia, and a down-regulation of IRS-1 expression.

Adenoma, Liver Cell↗
PubMed1999

Dehydroepiandrosterone increases the zone [correction of in zone] of glutamine synthetase-positive hepatocytes in female rat liver: a putative androgenic effect.

The adrenal steroid dehydroepiandrosterone (DHEA) is a hepatocarcinogen and peroxisome proliferator in the rat, producing an increase in peroxisomes mainly in perivenular parts of the liver lobule. Glutamine synthetase (GS) is expressed exclusively in hepatocytes that directly surround the central terminal vein in rat liver. The GS-positive zone is wider in males than in females, covering about two to three cell layers in males and one to two cell layers in females. Treatment of rats with DHEA at a concentration of 0.6% in the diet for 4, 20, 32, 70 and 84 weeks resulted in an enlargement of the GS-positive zone in females, whereas no change was observed in males. In females treated for up to 32 weeks with DHEA, the relative mean width (RMW) of the GS-positive zone was as large as that observed in males. The increase in the RMW was paralleled by an increase in the number of GS-positive hepatocytes. Upon longer treatment, the width of GS expression decreased to that observed in untreated controls. The findings suggest an androgenic effect of DHEA. The areas of peroxisome proliferation, identified in haematoxylin and eosin- and periodic acid-Schiff-stained sections, and GS expression were not identical. Furthermore, preneoplastic and neoplastic liver lesions induced by DHEA were all negative for GS, indicating that they do not derive from the perivenular cells which show the most pronounced peroxisomal proliferation.

Androgens↗
PubMed1999

Perception of the form of stimulus increment as a method in assessment of the psychophysical relationship.

Among numerous procedures for determination of the psychophysical relation, one approach has seldom been applied. Essential in this method is to present a set of stimuli whose intensity increases in fixed time following different forms. The objective stimulus increment, which the subjects perceive as linear growth directly, represents the inverse psychophysical relation. In this paper the method was tested in the fields of click frequency and sound pressure. This procedure was named "Perception of the Form of Stimulus Increment in Time". In comparison to other psychophysical approaches, this one has several advantages. The principal ones are the following: (1) In assessing the psychophysical relation it is not necessary to try to measure the perceptual magnitude; and (2) the psychophysical relation is directly determined by its dynamic pattern. In this paper modifications to the method are reported which facilitate the subject's task and avoid some differences in subjects' individual approaches to the task. The modified procedure leads to results satisfactory independent of the influence of the factors irrelevant to the psychophysical relationship.

Acoustic Stimulation↗
PubMed1998

Intracellular expression of Fc gamma RIII (CD16) and its mobilization by chemoattractants in human eosinophils.

We characterized the existence, translocation, and reabsorption during cellular activation of a constitutively expressed intracellular CD16 in the human eosinophil. By two-color flow cytometry, we showed that 6.5+/-0.3% of nonpurified eosinophils expressed surface CD16. After digestion with phosphatidylinositol-specific phospholipase C, surface CD16 on both neutrophils and eosinophils decreased substantially, suggesting that eosinophil CD16 is a glycosyl-phosphatidylinositol-linked isoform. However, CD16 was substantially expressed intracellularly in human eosinophils. Epitope-specific binding to CLB-gran11 mAb from non-NA2/NA2 donors demonstrated that intracellular eosinophil CD16 also differed from the transmembrane isoform of CD16 expressed on NK cells or macrophages. Western blot analysis performed with 3G8 or DJ130c mAb showed a broad band at approximately 65 to 80 kDa, which was the same as neutrophil CD16 from the same NA2/NA2 donors. Upon stimulation by chemoattractants C5a, FMLP, or platelet-activating-factor, eosinophilic intracellular CD16 was rapidly translocated to the eosinophil surface, expressed maximally at 30 s, and then gradually disappeared from the cell surface during the next 10 min. Intracellular flow cytometry of stimulated eosinophils and sandwich ELISA of stimulated eosinophil supernatants demonstrated that the disappearance was due to its rapid release into medium and reabsorption by the cells. Our data identify a CD16B that is consistently expressed intracellularly but only rarely on the surface of nonactivated human eosinophils. This CD16 is transiently expressed during stimulation by chemoattractants.

Blotting, Western↗
PubMed1998

Differential expression of key enzymes of energy metabolism in preneoplastic and neoplastic rat liver lesions induced by N-nitrosomorpholine and dehydroepiandrosterone.

Preneoplastic liver foci and neoplasms of different morphological phenotypes were induced in rats with N-nitrosomorpholine (NNM; 120 mg/l in drinking water for 7 weeks) and the peroxisome proliferator dehydroepiandrosterone (DHEA; 0.6% in the diet for up to 84 weeks). Preneoplastic glycogen storage foci (GSF) occurred mainly upon treatment with NNM, and amphophilic cell foci (APF) were mainly observed in rats treated with DHEA alone or in combination with NNM. The 2 types of lesions belong to 2 different cellular lineages, the glycogenotic/basophilic lineage and the amphophilic lineage, which are characterized by distinct patterns of alterations in key enzymes of energy metabolism. Whereas in GSF enzymes of glucose metabolizing pathways were modified (increase in glucose-6-phosphate dehydrogenase and pyruvate kinase, decrease in glucose-6-phosphatase), APF mainly demonstrated alterations in mitochondrial enzymes (increase in cytochrome c oxidase, succinate dehydrogenase and glycerol-3-phosphate dehydrogenase) and, to a lower extent, in peroxisomal enzymes (increase in peroxisomal hydratase and acyl-CoA oxidase). The alterations in enzyme expression reflect an insulinomimetic effect in GSF and a thyromimetic effect in APF. Neoplasms resulting from APF show a more differentiated phenotype than those arising from GSF. We suggest that the different and in many aspects opposite effects of the 2 carcinogens on key enzymes of distinct pathways of energy metabolism modulate the process of neoplastic liver cell transformation and result in phenotypically different preneoplasias and neoplasias reflecting different cellular lineages.

Animals↗
PubMed1998

Cytochemical and biochemical studies on adenylate cyclase activity in preneoplastic and neoplastic liver tissue and cultured liver cells.

The ATP-analogue adenylyl(beta,gamma-methylene)diphosphonate was chosen as substrate for the cytochemical localization of adenylate cyclase (AC) activity. The tissues investigated covered normal rat liver and liver from carcinogen-treated animals with preneoplastic lesions and hepatocellular neoplasms, as well as cultured liver cells. The AC reaction product methylene diphosphonate was precipitated with Pb2+ immediately at the place of production. This approach permitted a precise localization of AC activity by light and electron microscopy. The specificity of the AC reaction was demonstrated by control reactions, including inhibition of AC with 2'5'-dideoxyadenosine and activation with forskolin, glucagon, and cholera toxin. Endogenous phosphatases were inhibited with tetramisole and NAD. In normal liver, AC activity was mainly localized in the sinusoidal membrane of hepatocytes. A distinct gradient in activity was observed within the liver lobule. Hepatocytes localized around the terminal hepatic venule showed a significant higher AC activity compared to hepatocytes near the portal tract. AC was clearly decreased in focal preneoplastic liver lesions of the glycogenotic-basophilic cell lineage leading to hepatocellular carcinomas. Cytochemically detected intensity of AC activity corresponded to data obtained by microbiochemical assays in laser-dissected tissue samples. A remarkable interdependence of AC activity and degree of differentiation was also seen in epithelial rat liver cell lines: Highly differentiated cells show high enzyme activity and vice versa, as shown by both cytochemical and biochemical examinations. It is concluded that alterations in cellular signal transduction caused by alterations in AC activity play an important role in hepatocarcinogenesis.

Adenosine Triphosphate↗
PubMed1998

A new method for flat-embedding large native cryostat sections for targeting small preneoplastic lesions in comparative ultrastructural and ultracytochemical investigations.

Ultrastructural studies of rare and small cellular lesions in pathologically altered tissue are difficult to perform by applying conventional electron microscopic preparation. The search for lesions, often consisting of only a few cells in randomly obtained small specimen blocks, is time consuming and often without success. The methodological requirements for comparative enzyme cytochemical and morphological studies, i.e., preservation of both enzyme activity and ultrastructure, are divergent. By processing large native cryostat sections for electron microscopy, small preneoplastic focal lesions were successfully targeted in liver and kidney. Glucose-6-phosphatase, alkaline phosphatase, acid phosphatase, catalase, and cytochrome c oxidase activities were distinctly localized to endoplasmic reticulum, canalicular membrane, lysosomes, peroxisomes, and mitochondria, respectively, in the morphologically altered cells. Fixation of serial cryostat sections and enzyme reactions were both carried out through a semipermeable membrane except those for cytochrome c oxidase, which was demonstrated after fixation through the membrane by floating the section in incubation medium containing cytochrome c. Thereafter, the sections were flat embedded and polymerized between epoxy resin disks and aluminum dishes fitting exactly together. The objects of interest were identified in the light microscope, cut out, and reembedded in reversed gelatine capsules. By using this technique an ultrastructural preservation was achieved similar to that seen after immersion fixation. The enzyme activities were clearly localized without diffusion of the reaction product or unspecific deposits. The procedure permits precise targeting and complex studies of rare and small lesions, and opens new perspectives for the use of cryo-preserved tissue.

Animals↗
PubMed1998

Oral L-ornithine-L-aspartate therapy of chronic hepatic encephalopathy: results of a placebo-controlled double-blind study.

BACKGROUND/AIMS: In the current state of knowledge of the pathophysiology of hepatic encephalopathy, a reduction in hyperammonemia is the most important evidence of effective treatment. Therefore, the therapeutic efficacy of oral L-ornithine-L-aspartate, which improves impaired ammonia detoxification, was investigated in patients with cirrhosis, hyperammonemia and stable, overt, chronic hepatic encephalopathy, and in subclinical hepatic encephalopathy in a randomized, double-blind, placebo-controlled clinical trial. METHODS: Oral L-ornithine-L-aspartate was administered three times daily at fixed times for 14 consecutive days in a total dose of 18 g per day. The design was chosen to prevent an increase in ammonia induced by a protein meal of 0.25 g/kg body weight, given at the start of the daily treatment period. Efficacy variables were: fasting and postprandial ammonia concentration, Number-Connection-Test time, mental state grades, and a Portosystemic Encephalopathy Index. Analyses were based on the total study sample of 32 placebo- and 34 L-ornithine-L-aspartate-treated patients as well as on the subgroup samples in the overt (20 placebo- and 23 L-ornithine-L-aspartate-treated) and subclinical hepatic encephalopathy (12 placebo- and 11 L-ornithine-L-aspartate-treated) patients. RESULTS: Number Connection Test performance times (p<0.01) as well as fasting (p<0.01) and postprandial (p<0.05) venous blood ammonia concentrations in the L-ornithine-L-aspartate-treated group showed improvement in comparison to placebo. Also, the mental state grade (p<0.05) and the Portosystemic Encephalopathy Index (p<0.01), improved to a much greater degree in the L-ornithine-L-aspartate group than in the placebo group. Adverse events were observed in neither the placebo nor the L-ornithine-L-aspartate-treated patients. CONCLUSION: Oral L-ornithine-L-aspartate is a safe, well-tolerated treatment with a good compliance rate and a beneficial therapeutic effect in patients with cirrhosis and stable, overt, chronic hepatic encephalopathy.

Administration, Oral↗
PubMed1998

Nursing management of the patient with bone metastases.

OBJECTIVES: To review the problem of bone metastases and strategies aimed at the management of bone metastases. DATA SOURCES: Review articles, book chapters, research studies, and clinical practice. CONCLUSIONS: As patients survive for longer periods, effective management of bone metastases becomes critical to maintaining or improving quality of life. Controlling pain, preventing fractures and oncologic emergencies, and promoting mobility and function are the outcomes of successful management. IMPLICATIONS FOR NURSING PRACTICE: Use of a clinical algorithm may assist the nurse in identifying bone metastases and managing the clinical sequelae, such as pain.

Bone Neoplasms↗
PubMed1998

Does epidural analgesia cause dystocia?

STUDY OBJECTIVE: To analyze the effects of epidural analgesia for labor when dystocia occurs. DESIGN: Retrospective cohort study. SETTING: Academic health center. PATIENTS: 641 low risk, nulliparous women in spontaneous labor. INTERVENTIONS: 406 (63%) women received epidurals analgesia and 253 (37%) did not. Sixty women (9.4%) required an abdominal delivery for dystocia. MEASUREMENTS AND MAIN RESULTS: Women receiving epidural analgesia were more likely to be white, receive care from an attending physician, need labor augmentation, and deliver a heavier infant. Multivariate analysis identified five variables predictive of dystocia and abdominal delivery: pitocin augmentation odds ratio (O.R.) = 3.9 (2.0 to 7.6), duration of labor more than 20 hours O.R. = 2.4 (1.3 to 4.4), high epidural dose O.R. = 2.2 (1.2 to 4.1), birthweight over 4,000 grams O.R. = 2.0 (1.0 to 4.2), and early placement of epidural O.R. = 1. 9 (1.0 to 3.5). Repeating the regression after excluding the 20 women who developed abnormal labor prior to epidural placement (18 of 20 women had protracted dilatation) demonstrated that pitocin augmentation O.R. = 4.0 (1.8 to 4.), high epidural dose O.R. = 3.0 (1.9 to 6.2), duration of labor greater than 20 hours O.R. = 2.7 (1.3 to 5.7), and birthweight over 4,000 grams O.R. = 2.1 (0. 9 to 4.8) were associated with dystocia. CONCLUSION: Epidural analgesia appears to be a marker of abnormal labor rather than a cause of dystocia. High concentration anesthetics and epinephrine should be avoided, as they may influence labor. Randomized, controlled trials of this technique will be difficult to do; our work should reassure patients and their clinicians that epidural analgesia does not adversely affect labor.

Adult↗
PubMed1998

Vitamin E prevents induction of carbonyl group formation in microsomal protein by dehydroepiandrosterone.

The effect of dehydroepiandrosterone (DHEA), a free radical- and lipid peroxide-inducing agent, and of vitamin E (alpha-tocopherol), a free radical chain terminator, on protein carbonyl group formation was investigated in rat liver microsomes. Administration of alpha-tocopherol at 25-50 mg/kg diet for seven days resulted in high Fe(2+)-NADPH-ADP-dependent production of protein carbonyl groups in liver microsomal protein isolated from otherwise untreated rats. However, alpha-tocopherol administered at > 100 mg/kg diet caused a decrease in the production of protein carbonyl groups. In animals simultaneously receiving alpha-tocopherol at 50 mg/kg diet and DHEA at 500 mg/kg diet, no additional stimulatory effect of the steroid on microsomal protein carbonyl group production was observed. Protein carbonyl group production was significantly enhanced by DHEA in rats given a diet containing 400 mg alpha-tocopherol/kg diet. Microsomes isolated from rats fed 1,000 mg alpha-tocopherol/kg diet with DHEA (500 mg/kg diet) and without DHEA produced small but similar amounts of protein carbonyl groups. These results provide evidence that vitamin E is an important protective agent against DHEA-mediated oxidative damage of intracellular components, including proteins.

Adenosine Diphosphate↗
PubMed1998

Effects of oral dosing with calcium propionate on total calcium and glucose concentrations in the plasma of the cow.

This study aimed to determine the effect of oral drenching with molasses, calcium propionate and MgO on plasma glucose and calcium concentrations of dairy cows. Four trials were undertaken, each using three lactating and three non-lactating Jersey cows. In Trial 1, the effect of drenching with 200 ml molasses was measured. Trial 2 measured the effect of a single treatment with 349 g calcium propionate in 200 ml molasses. In Trial 3, the effect of 60 g MgO in molasses alone and in combination with calcium propionate was measured. Trial 4 tested the effect of repeating treatments with 349 g calcium propionate in 200 ml molasses 24 h apart. Dosing with 349 g calcium propionate in molasses increased plasma total calcium (Catot) concentration by 10% in lactating and non-lactating cows for periods less than 7 h, and this was not augmented by simultaneous administration of MgO or treatment 24 h earlier with 349 g calcium propionate in molasses. Treatment with 200 ml molasses alone resulted in increased plasma Catot of 7%. Plasma glucose concentrations were elevated by 11% for less than 3 h after treatment with calcium propionate. For the prevention of subclinical hypocalcaemia and ketosis in early lactation, drenching with calcium propionate solutions is unlikely to be of value due to the short duration of its effects, but the inclusion of calcium propionate in the postpartum ration deserves further investigation.

Administration, Oral↗