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Biomedical subjects

E Sander

Publications and source records attributed to E Sander.

At least 19 recordsLinked to original sources
PubMed1998

Calcium channel blockers and the risk of cancer: a preclinical assessment.

The preclinical evidence for a potential influence of calcium channel blockers (CCBs) on carcinogenesis is discussed in the light of a broad database from rodent carcinogenicity studies as well as literature data. In all bioassays performed in rats and mice on the dihydropyridine CCBs--nifedipine, nimodipine, nisoldipine, and nitrendipine--no evidence was found for a carcinogenic potential of these compounds. Calcium is an essential intracellular signal for cell proliferation and apoptosis. The crucial role of increased cell proliferation in all stages of carcinogenesis is well documented. Some indirect experimental evidence also points to a role of defective apoptosis in tumor promotion. CCBs uniformly inhibit cell proliferation, whereas the influence of CCBs on apoptosis is inconsistent, resulting in an inhibition or increase in apoptosis dependent on cell type. Accordingly, antitumorigenic effects of CCBs have been reported based on their antiproliferative action. A tumor-promoting effect of CCBs based on inhibition of apoptosis, however, remains purely speculative and, in fact, can be denied based on the results of in vivo bioassays. It is therefore concluded that there is no preclinical evidence that should give rise to concern over the carcinogenic potential of dihydropyridine-type CCBs.

Animals↗
PubMed1997

Analogical transfer as guided by an abstraction process: the case of learning by doing in text editing.

The authors proposed that not only are the first attempts to solve a problem made by analogy but also that progress in learning can be guided by referring to more abstract knowledge, which affords new possibilities. Two experiments investigated this view in a situation of learning how to use a text editor. Experiments 1A to 1C identified the knowledge associated with 3 domains hypothesized as sources of transfer at increasing levels of abstraction (typewriting, writing in general, manipulating objects). Experiment 2 tested whether participants first use their knowledge about typewriting, then about writing in general, and then about manipulating objects. The data showed that the order of acquisition of text editor functions appeared to be strongly related to this hierarchy, supporting the idea that part of learning consists of discovering properties of objects by accessing increasingly general domains.

Adult↗
PubMed1997

Clinical and pharmacokinetic study of oral etoposide in patients with AIDS-related Kaposi's sarcoma with no prior exposure to cytotoxic therapy.

PURPOSE: In this phase II and pharmacokinetic study, chronic, low-dose, oral etoposide was evaluated for its efficacy in patients with AIDS-related Kaposi's sarcoma who were not previously exposed to cytotoxic therapy. PATIENTS AND METHODS: Of 28 patients accrued for the study, 25 were assessable for toxicity and response. Twenty-four patients were male (homosexual or bisexual cases) and one patient was female (partner of a bisexual male). All patients were human immunodeficiency virus (HIV)-positive, New York University (NYU) disease stage IIB to IVB, and most exhibiting skin and lymph node and/or visceral disease. Median age was 33 years (range, 21 to 50), and median World Health Organization (WHO) performance status was 2 (range, 0 to 3). The patients received a mean number of six treatment courses (range, four to 27). Prior therapy included local/regional irradiation, immunotherapy (interferon-alpha), local resection, and/or cryotherapy. No prior cytotoxic therapy was allowed. Etoposide was administered at a schedule of 25 mg/m2 orally, twice a day for 7 days, every 2 weeks. Plasma concentrations of the drug were measured in six patients by a high-performance liquid chromatography (HPLC) method, after chloroform extraction using teniposide as internal standard. RESULTS: The overall response rate was 32% (two complete and six partial responses), and the median progression-free survival was 8 weeks (range, 4 to 27). Five patients (20%) had stable disease, while 12 cases (48%) did not respond. Patients without a history of opportunistic infections seemed to respond better. The regimen was well tolerated. The main toxic effects consisted of mild to moderate nausea and vomiting in approximately half of the cases, and WHO grodes 3 to 4 leukopenia and thrombocytopenia in eight of 25 (36%) and five of 25 (20%) of cases, respectively. However, only two patients had to discontinue treatment because of prolonged and severe neutropenia. No toxic deaths were documented. The pharmacokinetic analyses revealed the achievement of potentially therapeutic and lowly myelosuppressive plasma etoposide concentrations (2.1 micrograms/mL; range, 1.3 to 2.6) for a significant period of time, ie, for approximately 4.6 hours postdosing. CONCLUSION: At the schedule applied, etoposide shows significant objective antitumor activity in advanced AIDS-related Kaposi's sarcoma, and induces acceptable clinical toxicity. This apparent efficacy of the regimen could be a result of the prolonged maintenance of cytotoxic plasma concentrations of etoposide during each treatment course, and the absence of toxic peak levels of the drug. These results, together with the appreciable bioavailability of oral etoposide, make the regimen feasible for outpatient treatment of patients with advanced AIDS-related Kaposi's sarcoma. Further studies using the above-mentioned approach are warranted.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Long-term blockade of the angiotensin II receptor in renin transgenic rats, salt-loaded Dahl rats, and stroke-prone spontaneously hypertensive rats.

These studies were designed to investigate the protective effects of the new angiotensin II receptors antagonist BAY 10-6734 (6-n-butyl-4-methoxycarbonyl-2-oxo-1[(2'-(1H-tetrazol-5-yl) -3-fluorobiphenyl-4-yl)methyl] 1,2-dihydropyridine, CAS 156001-18-2) on haemodynamic, hormonal, renal, and structural parameters in renin transgenic rats (TGR(mRen2)27), salt-loaded Dahl S and R rats, and salt-loaded stroke-prone spontaneously hypertensive rats (SHR-SP) in long-term trials. Study 1: In SHR-SP the development of blood pressure, cardiac hypertrophy, and the deleterious effects of salt loading on kidney structure and kidney function was prevented by BAY 10-6734. Study 2: In salt-loaded Dahl S rats with a suppressed plasma renin activity treatment with BAY 10-6734 did not delay the increase in blood pressure but prevented cardiac hypertrophy and the increase in plasma ANP (Atrial natriuretic peptide). Study 3: TGR develop malignant hypertension associated with cardiac hypertrophy, elevated left-ventricular end-diastolic pressure and increased plasma ANP. After 6 weeks of treatment with BAY 10-6734 (30 mg/kg p.o. bid) cardiac pump function was improved and cardiac hypertrophy was reversed in this angiotension dependent form of hypertension. The beneficial effects of BAY 10-6734 in these different animal hypertension models are also emphasized by a reduction in mortality.

Aldosterone↗
PubMed1996

Granulocyte/macrophage-colony-stimulating factor induces the migration of human epidermal Langerhans cells in vitro.

In the present study, we investigated the in vitro migratory activity of human epidermal Langerhans cells (LC). Freshly isolated LC exhibit very low spontaneous migration. In contrast, a strong migration is recorded 6 h after the isolation. This migration is due to the presence of GM-CSF released by surrounding keratinocytes in vitro. Picomolar concentrations of GM-CSF promote the migration of LC, but nanomolar concentrations are inhibitory. Checker-board experiments indicate that GM-CSF acts as a chemokinetic mediator for LC, Bulk cultured LC exhibit a significant decrease of their spontaneous migration but retain the capacity to respond to GM-CSF only at nanomolar concentrations. In contrast, LC cultured in the presence of picomolar concentrations of exogenous GM-CSF exhibit a spontaneous migratory activity comparable to that of 6 h rested LC but do not respond to GM-CSF. These results suggest that GM-CSF represents an essential factor triggering the egress of LC from their epidermal environment.

Cell Movement↗
PubMed1995

Stabilization of erythrocytes by aldehydes and suitability of chicken IgY for the detection of potato virus X (PVX) in avidin-biotin enhanced reverse passive haemagglutination.

Methods are described for the detection of potato virus X (PVX) by reverse passive haemagglutination (RPH) by means of polyclonal antiviral antibodies coupled to sheep red blood cells (sRBC) and the chromic chloride method. The cells were stabilized with pyruvic aldehyde, thus providing a stock suspension for numerous coupling experiments lasting several months. Anti-PVX IgY, which is readily isolated in large amounts from the egg yolk of immunized chickens, was used in an avidin-biotin enhanced RPH assay with stabilized sRBC. With this method the PVX detection rate achieved was comparable to that of RPH assays using fresh non-fixed sRBC. In addition, avidin-coated sRBC could be stored for weeks at 4 degrees C and subsequently used for coupling with biotinylated IgY.

Animals↗
PubMed1995

Characterization of the protein tyrosine phosphatase CD45 on human epidermal Langerhans cells.

Human Langerhans cells (LC) express CD45, but clear data about the isoform(s) and their function(s) are lacking. In the present study, double labeling experiments reveal that freshly isolated LC from normal skin are CD45RO+/RA-/RB-. However, after isolation and short-time culture where LC undergo an in vitro maturation resembling that to lymphoid dendritic cells, CD45RB emerges whereas CD45RO expression decreases. This evolution results from dynamic alternative RNA splicing. Addition of granulocyte-macrophage colony-stimulating factor or tumor necrosis factor-alpha to short-time cultures has no significant effect on CD45RB, but both cytokines accelerate the loss of CD45RO. LC isolated from lesional skin of atopic eczema highly express CD45RO and CD45RB. Cross-linking of CD45 on LC isolated from atopic individuals inhibits the calcium mobilization in response to activation via Fc epsilon receptor type I (Fc epsilon RI). Hence, the protein tyrosine phosphatase CD45 from human LC is subjected to a splicing phenomenon related to the differentiation and activation stage of these cells and regulates their Fc epsilon RI-mediated activation.

Calcium↗
PubMed1993

Electroretinographic assessment of early retinopathy in rats.

Amoscanate, a substance which damages photoreceptors, was administered orally to Wistar rats in doses of 10, 40, and 125 mg/kg body weight once daily for 3 or 10 days. At both times electroretinographic, ophthalmological, and histopathological examinations of the retina were carried out to compare the sensitivity of conventional methods and to test electroretinography (ERG) for suitability for use in toxicity studies. Time-dependent and dose-dependent effects were found by electroretinography and light microscopy. However, signs of retinal changes appeared earlier and more distinctly in the electroretinogram. Ophthalmological fundus examination in albino rats yielded no characteristic correlate. In conclusion, electroretinography constitutes a valuable supplement to histopathology and is suitable for use in toxicity studies.

Animals↗
PubMed1992

CD69, an early activation antigen on lymphocytes, is constitutively expressed by human epidermal Langerhans cells.

When screening skin cryosections with a panel of monoclonal antibodies (MoAb), we found that the anti-CD69 MoAb Leu-23 reacted with a subpopulation of epidermal dendritic cells, presumably Langerhans cells (LC). The staining intensity was enhanced by gentle trypsin pretreatment of the sections. Flow cytometric analysis of LC-enriched epidermal cells (EC) revealed that nearly all CD1a-bearing LC display anti-CD69 reactivity when tested briefly after termination of the enrichment procedure. Immunoprecipitation experiments showed that isolated LC specifically express a disulphide-linked dimer composed of 26/30kDa subunits that therefore slightly differs from the 28/32kDa CD69 complex described on activated T or natural killer (NK) cells. This difference is probably due to a different post-translational glycosylation pattern as evidenced by Endoglycosidase-F treatment of the immunoprecipitate disclosing the 24-kDa core protein of CD69. When freshly isolated LC-enriched EC were kept in culture, anti-CD69 reactivity gradually decreased but the addition of IFN-gamma to the culture medium sustained the CD69 expression on LC in vitro. These results strongly suggest that resident but not LC recovered from EC cultures bear CD69 moieties. It remains to be seen whether the expression of this antigen can be linked to (a) particular functional property (ies) of intraepidermal LC.

Antibodies, Monoclonal↗
PubMed1992

Osteochondroma in laboratory rats: a report of 3 cases in a Fischer-344, a Sprague-Dawley, and a Wistar rat.

Three cases of osteochondroma in a male Sprague-Dawley (SD) rat, a female Fischer (F344) rat, and a male Wistar rat are described. The rats were aged between 26 and 30 months. All osteochondromas were considered to be of spontaneous origin. The Wistar rat had multiple osteochondromas on both hind legs, the skull base, and a lumbar vertebra, whereas each of the F344 and SD rats was affected by a solitary osteochondroma, also on a lumbar vertebra. The lumbar osteochondromas were similar in appearance in all rats and consisted of a central core of trabecular bone, interspersed with fatty marrow and covered by a cap of hyaline cartilage. The additional tumors in the Wistar rat represented different developmental stages of osteochondroma with or without endochondral activity. The osteochondromas in the rats were morphologically similar to those described in humans and some domestic animal species.

Animals↗
PubMed1992

Monoclonal antibody to tumor necrosis factor--alpha prevents lethal endotoxin sepsis in adult rhesus monkeys.

In a rhesus monkey endotoxin sepsis model established by intravenous administration of 300 mg/kg D-galactosamine and 0.1 microgram/kg lipopolysaccharide from Salmonella abortus equi, hemodynamic, respiratory, metabolic and hematologic variables; levels of blood gases; monkey leukocyte elastase levels, and blood plasma concentrations of tumor necrosis factor--alpha (TNF) were monitored for 6 hours after administration, and again after 24 hours. Thirty minutes after administration of lipopolysaccharide, either 15 mg/kg anti-TNF monoclonal antibody (MoAB; n = 6) or vehicle placebo (saline solution; n = 4) were given intravenously. During this short-term experiment the organ functions were not different between the treatment groups. However, anti-TNF MoAb afforded morphologic protection from heart, lung, liver, and kidney damage after lipopolysaccharide challenge. Coagulation responses (platelet count and levels of fibrinogen, antithrombin III, and thrombin-antithrombin III complex) were smaller in anti-TNF MoAB-treated monkeys. Plasma TNF levels (WEHI cell cytotoxicity assay) reached a peak (350 pg/ml) 60 minutes after lipopolysaccharide administration in vehicle control subjects but no TNF was detected in the anti-TNF MoAB-treated monkeys. All control animals died 67 +/- 30 hours after lipopolysaccharide administration from multiorgan failure. On the contrary, all anti-TNF MoAB-treated animals survived 14 days (p > 0.005 vs placebo group mortality). Thus in short-term monkey experiments our study indicates protection against lipopolysaccharide-induced endotoxin sepsis by anti-TNF MoAB, which may have clinical relevance for the treatment of human septicemia.

Acid-Base Imbalance↗
PubMed1991

Phase II study of teniposide in patients with AIDS-related Kaposi's sarcoma.

Antitumour activity of cytotoxic agents, evaluated in patients with AIDS-related Kaposi's sarcoma (KS), is about 30-80%. However, responses are mostly partial and short. Experience with etoposide is similar. Teniposide has a longer elimination half-life and superior antitumour activity compared with etoposide in some experimental models. Thus a phase II trial was done in 25 patients with AIDS-related KS. Teniposide was given by 60-min infusion at 360 mg/m2 every 3 weeks. 10 (40%) showed a partial response, median duration of 9 (6-20) weeks. The main side-effects were leukopenia, thrombocytopenia, nausea and vomiting, alopecia and mucositis.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Effect of postural stimulation on systemic hemodynamics and sympathetic nervous activity in systemic hypertension.

The contributions of the carotid sinus and cardiopulmonary baroreflexes to the interindividual variation in sympathetic nervous system activation caused by postural adaptation were indirectly assessed in 68 mild hypertensive subjects. Supine and upright plasma norepinephrine (NE), blood pressure (cuff) and cardiac output (acetylene rebreathing) were measured. Mean arterial pressure (MAP), carotid sinus pressure, stroke volume and systemic vascular resistance were calculated. Stroke volume was assumed to be proportional to the degree of stretch of cardiac mechanoreceptors, carotid sinus MAP was assumed to be proportional to carotid sinus stretch and plasma NE to reflect sympathetic nervous activity. Plasma NE correlated inversely with stroke volume (r = -0.62, p less than 10(-14] and estimated carotid sinus MAP (r = -0.33, p less than 0.0002) and positively with systemic vascular resistance (r = 0.59, p less than 10(-10]. Holding systemic vascular resistance constant by partial regression, the inverse relation between plasma NE and stroke volume remained (partial r = -0.36, p less than 0.02). Multiple linear regression yielded the equation: plasma NE (pg/ml) = 720 + 4.3 age - 5.1 stroke volume (ml) - 1.0 carotid sinus MAP (mm Hg). Substituting mean supine and upright values for stroke volume and carotid sinus MAP in this equation, it can be roughly estimated that changes in stroke volume account for as much as 60% of the postural variation in plasma NE in hypertensives, whereas only 15% of this variation is caused by changes in carotid sinus pressure. These findings suggest that cardiopulmonary baroreflexes are primary activators of the sympathetic nervous system during postural adaptation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Hemodynamics of seasonal adaptation.

To investigate the possibility that seasonal adaptation requires significant hemodynamic changes, 5 normotensive and 21 mildly hypertensive subjects were followed through 4 seasons for changes in systemic hemodynamics and sympathetic nervous activity. In the upright position wintertime blood pressures increased by 3% (P = NS) over summer values whereas cardiac output and stroke volume decreased by 18% and 21%, respectively (P less than .0017 for each). Similarly, wintertime upright heart rate increased by 7% (P less than .017) with larger parallel increases in systemic vascular resistance (+24%, P less than .0017) and plasma norepinephrine (+26%, P less than .017). The supine values followed similar trends but the magnitude of changes was about 50% less than the corresponding upright values. Thus, in the northern US, wintertime vasoconstriction is related to increased sympathetic nervous activity and decreased cardiac output. When these reciprocal changes are proportional, blood pressure remains constant.

Adaptation, Physiological↗
PubMed1990

Characterization of Bay U 3405, a novel thromboxane A2/endoperoxide receptor antagonist.

The thromboxane A2-receptor antagonistic properties of Bay U 3405 [(3R)-3-(4-fluorophenylsulfonamido)-1,2,3,4-tetrahydro-9-carbaz o-lepropanoic acid] have been evaluated in various pharmacologic models. Bay U 3405 specifically inhibits platelet aggregation induced by U 46619, collagen, platelet-activating factor, and the second wave of ADP (IC50 0.5, 0.07, 0.3, 0.19 microM) in human plasma. The plasma phase of ADP-induced aggregation is not affected. U 46619-induced platelet aggregation is competitively antagonized (pA2 = 6.3). In humans, ex vivo platelet aggregation is inhibited after oral application of 2 or 50 mg Bay U 3405. Bay U 3405 also specifically and competitively antagonizes U 46619-induced contractions of rabbit aortic rings (pA2 = 7.4). In vivo, Bay U 3405 protects rabbits dose dependently from arachidonic acid or collagen-induced thromboembolism (ED50 1-3 mg/kg p.o). Chronic administration of Bay U 3405 to stroke-prone spontaneously hypertensive rats reduces stroke-related mortality and diminishes the occurrence of cerebral hemorrhages. From these results, we conclude that Bay U 3405 is an orally active, selective, and competitive thromboxane A2-receptor antagonist that may be beneficial in the treatment of cardiovascular or cerebrovascular diseases.

Adenosine Diphosphate↗