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Biomedical subjects

D Mayer

Publications and source records attributed to D Mayer.

At least 199 records · Page 11Linked to original sources

Two sites of intracellular localization of rhodaminyl-phalloidin in hepatocytes.

The uptake of a fluorescent phallotoxin (tetramethylrhodaminyl-phalloidin) into rat hepatocytes has been studied. The experiments were performed in vitro, using freshly isolated hepatocyte suspensions or monolayers of hepatocytes cultured for up to 5 days, as well as in vivo, by investigating cryostat sections of a liver from an animal injected with the labelled toxin. In vitro, in freshly isolated hepatocytes, a staining of actin was observed. On the contrary, if the hepatocytes were cultured, only fluorescent endocytotic vesicles were found accumulated around the nucleus, and remaining in the cells unchanged for several days. In vivo, both fluorescent patterns were observed, often in one and the same cell. The endocytotic vesicles of rhodaminylphalloidin looked very similar to those obtained with fluoresceinyl-concanavalin A. navalin A. We conclude that in all systems the fluorescent phallotoxin enters the hepatocytes by endocytosis. However, in the freshly isolated cells the endocytotic vesicles apparently undergo some kind of processing with release of the toxin and subsequent staining of cellular actin, while in cultured hepatocytes the endocytotic vesicles persist unprocessed.

Animals↗

Recombinant leukocyte A interferon in advanced breast cancer. Results of a phase II efficacy trial.

Nineteen patients with advanced refractory metastatic breast cancer no longer responsive to chemotherapy were treated in the first phase II efficacy trial of recombinant leukocyte A interferon (IFL-rA), a highly purified single molecular species of alpha interferon prepared by recombinant DNA methods. Patients received a previously determined maximum tolerated dose for this agent (50 X 10(6) U/m2 body surface area) by intramuscular injection three times weekly for up to 3 months. The symptoms of toxicity observed in this trial resemble those previously reported for alpha interferons and include fever, chills, fatigue, anorexia, and leukopenia. All patients required dose reductions, most often for reasons of severe fatigue. Of the 17 patients evaluable for tumor response, one patient had stable disease and 16 had evidence of tumor progression. We conclude that IFL-rA is not an active agent in the treatment of advanced, refractory breast cancer when used at a maximum tolerated dose on this treatment schedule.

Adult↗

Biochemical correlation of glycogen content and activity of some enzymes of carbohydrate metabolism in rat liver during early stages of carcinogenesis.

The livers of rats treated for 12 weeks with N-nitrosomorpholine (80 mg/1 drinking water) were investigated on the day of carcinogen withdrawal (12 + 0 weeks) and 8 weeks after cessation of treatment (12 + 8 weeks). The glycogen content in relation to the DNA and protein content of the liver and the activities of glycogen synthetase, glycogen phosphorylase, glucose-6-phosphatase, and glucose-6-phosphate dehydrogenase were determined in the liver homogenates. The glycogen content of the livers was slightly elevated at both times investigated. Phosphorylase and synthetase activities showed no clear alterations in livers of treated animals as compared with controls. Glucose-6-phosphatase activity was significantly reduced at 12 + 0 weeks and returned to normal values at 12 + 8 weeks. The activity of glucose-6-phosphate dehydrogenase was unchanged at 12 + 0 weeks, but exhibited a significant increase at 12 + 8 weeks. Polyacrylamide gel electrophoresis with staining of the gels by an assay specific for the glucose-6-phosphate-dehydrogenase-catalysed reaction revealed the same pattern of active bands in treated and untreated animals but with higher activities in two bands originating from extracts of nitrosomorpholine-treated livers.

Animals↗

Single dose pharmacokinetics of fendiline in humans.

Fendiline was administered intravenously (3 mg) and orally (50 mg and 75 mg) in a cross-over study to six healthy volunteers. The plasma levels of unchanged fendiline and of total radioactivity were measured. Fendiline was absorbed well and its concentration declined biexponentially with mean terminal half-lives of 20-35 h. Since the drug is extensively metabolized, only 12% of total radioactivity in plasma corresponded to fendiline in the case of intravenous administration as compared to less than 2% after oral administration. 56-65% of the administered dose are excreted via the urine and 18-25% with the feces within five days.

Adult↗

The cytoskeleton in tumor cells.

During the past few years several laboratories investigated the occurrence of cytoskeletal components in epithelial and mesenchymal cells by electron microscopy and/or immunocytochemical methods in a number of tumor types growing in vitro or in the body. Since it is well established that antibodies to different intermediate-sized filament proteins can distinguish cells and tissues of epithelial, mesenchymal, muscle, astrocytic and neural origin special attention has been paid to the behaviour of these filaments in neoplastic cells recently. While the organisation of the cytoskeleton in tumor cells growing in vitro is very variable, regularities relevant for the diagnosis and the determination of the histogenetic origin of tumors have been observed in tumor cells growing in the body. In general, ultrastructural and immunological features of intermediate filaments are maintained during neoplastic transformation in the body. Thus immunofluorescence microscopy with antibodies to cytoskeletal proteins is a powerful tool for the classification and differential diagnosis of tumors, especially for the distinction between epithelial and mesenchymal tumors, including metastases. The concept that presence of an excess of contractile proteins such as actin is an important prerequisite for the metastatic spread of malignant cells has not been unequivocally supported by more recent results. However, an accumulation of various types of intermediate filaments (e.g. prekeratin, vimentin, acidic glial fibrillar protein) has been shown in different tumor types. The further elucidation of this alteration could contribute to a better understanding of the molecular mechanisms of neoplastic cell transformation.

Adenoma, Bile Duct↗

Correlative histochemistry of some enzymes of carbohydrate metabolism in preneoplastic and neoplastic lesions in the rat liver.

The livers from a total of 51 Sprague-Dawley rats treated with different doses of N-nitrosomorpholine (80-120 mg/l in the drinking water) for up to 14 weeks together with the livers of 28 control animals were histochemically investigated at the cessation of carcinogenic insult and at varying periods thereafter for their glycogen content, basophilia and activities of various enzymes of carbohydrate metabolism: glycogen synthetase, glycogen phosphorylase, glucose-6-phosphatase, glyceraldehyde-3-phosphate dehydrogenase and glucose-6-phosphate dehydrogenase. The enzymatic patterns of normal tissue, preneoplastic and neoplastic lesions were characterized and compared with reference to the morphologically defined stages of tumor development in the liver. The early appearing glycogen storing areas, localized in the peripheral and intermediate lobular regions, did not show significant changes in the histochemically demonstrable activities of the enzymes tested. After cessation of the carcinogen treatment the more pronounced glycogen storage foci which developed within the aforementioned regions of the liver acinus usually showed a reduction in the activities of phosphorylase and glucose-6-phosphatase while the activity of glucose-6-phosphate dehydrogenase, a key enzyme for the pentose phosphate pathway, was increased. The mixed cell foci, neoplastic nodules and tumors which emerged at later stages were characterized by a progressive shift away from glycogen metabolism towards glycolysis and the pentose phosphate pathway, as indicated by an increase in glyceraldehyde-3-phosphate dehydrogenase and glucose-6-phosphate dehydrogenase activities. These changes in enzyme pattern are supportive of a developmental sequence leading from glycogen storage foci through mixed cell foci and neoplastic nodules to hepatocellular carcinomas.

Animals↗

The dose dependence and sequential appearance of putative preneoplastic populations induced in the rat liver by stop experiments with N-nitrosomorpholine.

Different doses of N-nitrosomorpholine (NNM) (80, 120, 160, 200 mg/l drinking water) were administered for various periods of time (1, 4, 7, 14, 20 weeks) to male Sprague-Dawley rats in order to investigate the dose dependence and sequential appearance of preneoplastic and neoplastic lesions in the liver. With all dose levels studied a sequence was established leading from clear cell and acidophilic cell glycogen storage foci through mixed cell foci and neoplastic nodules to hepatocellular carcinomas. The first appearance and frequency of the different lesions investigated proved dependent on dose of carcinogen administered. Morphometric analysis demonstrated that the rare small clear cell foci apparent after 7 weeks treatment with NNM increase in number and size with progression through the sequence to carcinomas without further administration of carcinogen. No evidence was found to suggest that pronounced focal populations were reversible upon cessation of NNM-treatment under the present experimental conditions.

Animals↗

[Nurses in the psychiatric department of a community hospital].

Anyone who tries to convert a Psychiatric Department into a hospitable home for the benefit on the inmates and their environment, has quite often not reckoned with, the "host", that is to say, with the doctors, nurses and the hospital staff in general. Hence, it seems that a fundamental change in the attitude and consciousness of those who are engaged in psychiatry, is just as important as a new treatment concept or a new building. The author quotes the Bad Driburg Community Hospital as an example: here, planning and construction were not the only important factors. The nurses have taken and accepted advice with regard to their supervisory functions, and in the course of a protracted process they have changed their attitude in favour of a psychiatric practice which follows a treatment pattern based on a "open-minded" approach to community members.

Attitude of Health Personnel↗

A new histochemical method to assess and evaluate potential bone marrow damage from therapeutic substances.

A new model is presented for assessing and evaluating the influence of bone-marrow-damaging substances in mice. Qualitative and quantitative results of histological, histochemical and enzyme histochemical studies facilitate the assessment of bone marrow damage in terms of extent and intensity. Bone marrow taken from the right femur of treated animals was embedded in renal tissue of controls for subsequent work-up in different techniques. From each of the experimental groups specimens from 10 animals were frozen in liquid nitrogen, specimens from another 10 animals were fixed in buffered formalin. Assessment and evaluation of changes was performed after the required histologic and histochemical staining (nucleic acid). Results were correlated with the cytology of bone marrow smears sampled from the left femur of each respective animal. Damage was visualized, in smear cytology or in histologic and histochemical preparations, and quantified by microphotometry and special staining for cytochrome oxidase activity.

Animals↗

[Neoplastic and preneoplastic lesions in rats after oral administration of a single dose of N-nitrosomorpholine (author's transl)].

The administration of a single oral dose of 320 mg/kg body wt. N-nitrosomorpholine (NNM) to 62 Sprague-dawley rats resulted in neoplastic and preneoplastic changes in different organs, especially in liver and kidney. After a lag period of 4 weeks, nearly all experimental animals developed preneoplastic (clear cell, acidophilic, basophilic, mixed cell) foci of the liver parenchyma. Sporadically, small neoplastic nodules were found in the liver as early as 4 weeks after the beginning of the experiment. After a lag period of 1--2 years, 4 of 13 rats showed multiple neoplastic hepatic nodules and one animal a hepatocellular carcinoma. The bile ductules of some animals responded to the carcinogen by forming mucous cholangiofibroses and cystic cholangiomas. After long lag periods, large cholangiofibromas were found in two experimental animals. One or two years after application of the carcinogen, many animals developed epithelial (clear cell, acidophilic, chromophobic, basophilic, oncocytic) kidney tumors, often cystic. Pathologically changed (clear cell, chromophobic, basophilic, oncocytic) tubules are regarded as precursors of the epithelial tumors. The latered tubules appear for the first time at about half a year after application of the carcinogen. Apart from multiple cysts of the liver and kidneys some pancreatic cysts developed in two animals. In addition, two mesenchymal kidney tumors, one malignant neurinoma, two subcutaneous fibromas, one fibroadenoma, and one squamous cell carcinoma of the skin were observed.

Administration, Oral↗