Biomedical subjects

K Kramer

Publications and source records attributed to K Kramer.

At least 109 records · Page 6Linked to original sources

PubMed1990

Effect of PO2 and metabolic inhibitors on ionic fluxes across the isolated rabbit corneal endothelium.

Bicarbonate and sodium fluxes were measured across the isolated rabbit corneal endothelium under the influence of several inhibitors. Depression of PO2 in the bathing medium decreased net sodium movement but increased bicarbonate movement. Furosemide did not alter bicarbonate fluxes at either 10(-4) or 10(-5) M, but increased passive sodium flux leading to a decrease in net flux. Thiocyanate, at 5 x 10(-3) or 5 x 10(-2) M, decreased active bicarbonate flux and hence net flux, but had no effect on sodium fluxes. Dinitrophenol increased only the passive bicarbonate flux while decreasing both active and passive sodium fluxes, albeit unequally, leading to a decreased net flux. Ethacrynic acid affected only passive bicarbonate flux, while decreasing net sodium flux. The stilbene derivatives, SITS and DIDS caused opposite effects on both sodium and bicarbonate fluxes. SITS decreased net bicarbonate flux by decreasing active and increasing passive flux, yet increased net sodium flux. DIDS, however, increased net bicarbonate flux but decreased net sodium flux. The results may be explained by current models for endothelial ion transport that include a Na+/H+ antiport and a HCO3-/Na+ symport system in parallel with an independent pathway for HCO3- exit from the endothelial cells. When compared with prior corneal swelling data using these same inhibitors, the maintenance of corneal thickness appears to be dependent on the variation of ion fluxes from normal values, and the dissociation of the two active ion fluxes. In addition, there appears to be a significant ability of ion transport systems to compensate for disturbances to other ion exchange or transport mechanisms.

Animals↗

PubMed1988

Vitamin E and selenium regulate balance between beta-adrenergic and muscarinic responses in rat lungs.

The effects of hydrogen peroxide on the beta-adrenergic and muscarinic responses of the rat trachea muscle were studied in vitro, after feeding rats, for 6 weeks, either a diet deficient in vitamin E and selenium or a control diet. In the control situation after incubation with 1 mM hydrogen peroxide for 30 min, a reduction of the maximal response to methacholine of 39% occurred whereas no pD2 shift could be demonstrated. Moreover, no response to isoprenaline after precontraction with 3 x 10(-7) M methacholine was left. In the deficient situation, we found a reduction to 64% of the response to methacholine after incubation with 1 mM hydrogen peroxide. Again isoprenaline became inactive, i.e. no relaxation with isoprenaline was observed after precontraction with 3 x 10(-7) M methacholine. We therefore conclude that vitamin E and selenium protect against oxidative stress in lung tissue and thus regulate the (patho-) physiological balance between adrenergic and muscarinic responses.

Animals↗

PubMed1988

Irreversible binding of the fluorescent beta-adrenoceptor probes alprenolol-NBD and pindolol-NBD to specific and non-specific binding sites.

The fluorescent 4-nitrobenzo-2-oxa-1,3-diazolyl (NBD) derivatives of alprenolol and pindolol bind irreversible to beta-adrenoceptors and non-receptor binding sites. This was established in functional experiments on the guinea pig right atrium and trachea smooth muscle, and by radioligand binding assay of beta-adrenoceptors on Chang liver cells in culture. The pD2'-values of alprenolol-NBD and pindolol-NBD for the beta-adrenoceptors on the right atrium were: 8.3 +/- 0.1 and 8.5 +/- 0.1; on the tracheal smooth muscle strip: 8.2 +/- 0.1 and 8.8 +/- 0.1; and its pKd on Chang liver cells: 8.5 +/- 0.1 and 8.9 +/- 0.1 respectively. The results indicated that no selectivity for the beta-adrenoceptor subtypes was introduced by the addition of NBD. The irreversible binding characteristic to beta-adrenoceptors and non-receptor binding sites of the fluorescent NBD derivatives of alprenolol and pindolol makes these drugs unsuitable to label beta-adrenoceptors specifically. As the irreversible binding is introduced by the coupling of the drug with NBD, it is concluded that NBD derivatives of beta-adrenoceptor antagonists are not suitable to visualize the two-dimensional motion of beta-adrenoceptors during challenge with agonists.

4-Chloro-7-nitrobenzofurazan↗

PubMed1987

The effect of ischemia and recirculation, hypoxia and recovery on anti-oxidant factors and beta-adrenoceptor density. Is the damage in the erythrocytes a reflection of brain damage caused by complete cerebral ischemia and by hypoxia?

This investigation was focussed on the gravity of tissue injury caused by complete ischemia (for five min) and hypoxia (for three weeks) in the cerebral cortex (homogenate) and the erythrocyte lysate or the erythrocyte membrane of the rat in order to investigate if the changes that occur in brain tissue are reflected in the erythrocyte. To this end, glutathione (GSH), superoxide dismutase (SOD) and catalase were measured, also alterations in beta-adrenoceptor density under these two conditions were examined. It was found that in ischemia partial parallelism in changes that occur in the central nervous system (cerebral cortex) and the erythrocyte exists. The SOD activity became higher and the beta-adrenoceptor density (measured as specific (-)-[125I] iodocyanopindolol binding) was decreased in both tissues. However after the hypoxic condition we established a decrease in the number of beta-adrenoceptors in the cerebral cortex but an increase in beta-adrenoceptor density in the erythrocyte.

Animals↗

PubMed1987

Functional reconstitution of N-methyl-D-aspartate receptors in artificial lipid bilayers.

Functional reconstitution of the N-methyl-D-aspartate (NMDA) receptors was achieved by adding synaptic membranes from rat brain to large planar bimolecular lipid membranes (BLMs). The reconstituted receptors exhibited several properties of the NDMA receptors described using a variety of biochemical and electrophysiological techniques. Addition of NMDA at concentrations between 5 and 50 microM produced large, voltage-dependent increases in membrane conductivity. The selective antagonist of NMDA receptors, amino-2-phosphonopentanoate (AP-7), totally blocked the response of the bilayers to NMDA as did micromolar concentrations of magnesium; this latter effect was also voltage-dependent. These results indicate that BLMs can be used to study the ion channels and regulatory processes associated with NMDA receptors from adult brain in ways that could not be accomplished with conventional neurophysiological techniques.

Aspartic Acid↗

PubMed1987

A disbalance between beta-adrenergic and muscarinic responses caused by hydrogen peroxide in rat airways in vitro.

The effect of hydrogen peroxide on adrenergic and muscarinic responses of rat airway smooth muscle was studied. The trachea muscle and the lung parenchymal strip were contracted with methacholine and relaxed with (-)-isoprenaline. Recording of three (-)-isoprenaline curves on the trachea muscle and the lung parenchymal strip was followed by treatment for 30 min with hydrogen peroxide (H2O2) (1mM) after which a new dose response curve for (-)-isoprenaline was constructed. Using the trachea muscle this treatment with H2O2 resulted in a decrease of 61% of the maximum contraction by methacholine compared with the control and a complete inhibition of the relaxation by (-)-isoprenaline. In the lung parenchymal strip preparation we found, after the same treatment no reduction of the contraction by methacholine and 61% reduction of the relaxation by (-)-isoprenaline, compared with the control. The results demonstrate that the adrenergic response in rat airways is more susceptible to hydrogen peroxide than the muscarinic response.

Animals↗

PubMed1987

Relation between pharmacological response and receptor binding with histamine blocking drugs. Irreversible antagonism of three analogues of mifentidine on right atrium and cerebral cortex of the guinea-pig.

The effects of the H2-receptor antagonists cimetidine, ranitidine, mifentidine and three analogues of mifentidine, were studied on the spontaneously beating right atrium (H2-antagonism) and membranes of the cerebral cortex (displacement of 3H-tiotidine), both obtained from the male guinea-pig. The choice of these compounds was based on preliminary experiments in which some mifentidine analogues were shown to displace tiotidine from the H2-receptor in a deviant manner. In the present study we investigated the relation between pharmacological response and receptor binding, also testing the degree of irreversible antagonism of these compounds in the atrium (functional) and cerebral cortex (binding) model. Our data indicate that a relation between the two different approaches for measuring the effect on the H2-receptor can be found, although some differences emerged as well.

Animals↗

PubMed1987

Malignant epithelioid hemangioendothelioma of the colon. Report of a case.

Angiosarcoma of the colon with epithelioid and histiocytoid features, a malignant counterpart of epithelioid hemangioendothelioma, was observed in a 72-year-old man. The disease first manifested as a right cervical mass, with the histologic appearance of malignant, undifferentiated, large-cell epithelioid neoplasm. Light microscopy of the colonic tumor disclosed angiosarcoma, with active erythrophagocytosis and positive immunoperoxidase reactions to lysozyme, alpha-1-antitrypsin, and alpha-1-antichymotrypsin. Ultrastructural features of the tumor cells were those of intermediate between endothelial and histiocytic cells. The disease took a rapid fatal course with recurrence, peritoneal dissemination, and massive peritoneal hemorrhage. The cause remains unknown.

Aged↗

PubMed1987

Studies on the active molecular species of the H2 receptor antagonists cimetidine and mifentidine.

The N'-(4-1H-imidazol-4-ylphenyl)formamidines were recently introduced as a new class of active H2 antagonists; the authors of the compounds (Donetti et al. of de Angeli, Italy) have suggested that these compounds interact with the H2 receptor through their monocations. This is at variance with the model proposed for cimetidine by the SK&F (Smith Kline & French, UK) group who proposed the neutral molecule as the species active at the H2 receptor. In the present study we have investigated the issue whether the neutral or charged species is the active one by measuring the pA2 values of mifentidine and cimetidine at different pH values. Changing the pH will influence the species equilibria of both compounds and thereby affect their activity. The activity changes measured for both compounds are consistent with the proposition that cimetidine as well as mifentidine elicit their activity through their neutral species.

Animals↗

PubMed1987

Family affair.

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Allied Health Personnel↗

PubMed1987

Vaginitis emphysematosa.

Vaginitis emphysematosa is rare, as only 173 cases, to our knowledge, have been reported in the English literature, the last in 1967. We report three new cases and bring the subject up to date. The ages of our patients ranged from 42 to 65 years; one patient complained of vaginal discharge, and the other two cases were found on routine examination, one at autopsy for breast carcinomatosis. The lesions were described as nodules in the vagina, on occasion producing a "popping sound" that relieved the pressure sensation. Microscopically, variably sized cysts were seen containing pink hyalinlike material and foreign body-type giant cells in the cyst's wall, accompanied by minimal chronic inflammatory cell infiltrate. Vaginitis emphysematosa is an uncommon self-healing disease of unknown cause that produces no sequelae deleterious to the patient.

Adult↗

PubMed1986

Influence of lipid peroxidation on beta-adrenoceptors.

The peroxidation of lipids in biological membranes is a destructive phenomenon that can be elicited in various ways. Surface receptor molecules that allow cells to respond to hormones are possibly inactivated during lipid peroxidation. Effects of lipid peroxidation on receptors have not been extensively examined thus far. This investigation shows that there is a decrease in beta-adrenoceptor density (measured as specific (-)-[125I]iodocyanopindolol binding) during lipid peroxidation, in both lungs and erythrocytes of the rat. To this end, lung membranes (containing both beta 1- and beta 2-adrenoceptors) and intact erythrocytes (containing a homogeneous beta 2-adrenoceptor population) were pretreated with cumene hydroperoxide (lung membranes with 0.1 mM and erythrocytes with 1 mM) and Fe2+ (1 X 10(-5) M) for 60 min which resulted in extensive lipid peroxidation measured as malondialdehyde formation. The ration beta 1-:beta 2-adrenoceptor density in lung membranes after treatment with cumene hydroperoxide did not change and remained at 30%:70%. A single injection (i.p.) with the herbicide paraquat (50 mg/kg, 24 h), which is known to cause lung damage via lipid peroxidation, resulted in similar alterations in receptor density to those caused by cumene hydroperoxide in the in vitro experiments.

Animals↗

PubMed1986

The effects of 4-hydroxy-2,3-trans-nonenal on beta-adrenoceptors of rat lung membranes.

Lung membranes are susceptible to oxygen radicals, formed during inflammation, redox cycling of toxic agents, exposition to ozon etc. Oxygen radicals may modify the beta-adrenergic response. However, at the same time beta-adrenoceptors of the lung are frequently addressed in therapy. We embarked upon this problem by studying the effects of the aldehyde 4-hydroxy-2,3-transnonenal (HNE), one of the major products of lipid peroxidation, on the density of beta-adrenoceptors of rat lung membranes. It is shown, that the physiological important sulfhydryl blocking agent HNE inactivates the beta-adrenoceptors in a time- and concentration dependent (0.5-2.5 mM) way, indicated by a decrease in (-)-[3H]dihydroalprenolol (DHA) binding to lung membranes. Moreover, it is shown that combined treatment of HNE with (-)-isoproterenol (0.5 microM) or 1-alprenolol (0.5-10 nM) does not influence the extent of inactivation of beta-adrenoceptors by HNE. This is in contrast with previous studies, conducted with other, synthetic, sulfhydryl blocking agents, such as N-ethylmaleimide (NEM), suggesting that an other mechanism of inactivation is involved upon HNE treatment.

Aldehydes↗

PubMed1985

High affinity non-beta-adrenoceptor binding of beta-adrenergic ligands.

Two types of saturable binding, besides the well-known non-specific binding, were found when hydrophobic ligands were used for investigating the vesiculization of beta-adrenoceptors on cultured HeLa and Chang liver cells. The first (compartment I) representing beta-adrenoceptors with high affinity ([3H]DHA 0.8 nM, 125I-CYP 27 pM) and low capacity (10-20 fmol/mg protein), the second (compartment II) had a rather high affinity ([3H]DHA 400 nM, 125I-CYP 30 nM) and a very high capacity (20 000-25 000 fmol/mg protein). The affinity of adrenergic agents for compartment II correlates very well (r = 0.9418) with the calculated hydrophobicity. It is concluded that these types of binding sites might interfere with the determination of adrenoceptor binding sites when hydrophobic ligands are used. When using hydrophobic ligands like these special care should be taken to avoid such interference.

Adrenergic beta-Agonists↗

PubMed1985

Non-specific binding of the fluorescent beta-adrenergic receptor probe alprenolol-NBD.

The fluorescent beta-adrenergic receptor probe alprenolol-NBD was found to exhibit a high affinity (Kd 3.2 nM) and a low capacity (10 fmol/mg protein) for the beta 2-adrenergic receptor on living Chang liver cells but also a high affinity (Kd 320 nM) for non-beta-adrenergic receptor binding sites with a very high capacity (28,000 fmol/mg protein). Calculations are presented which make clear that less than 3% of the binding of alprenolol-NBD during visualization experiments is beta-adrenergic receptor related. Furthermore, it is shown that besides the downregulation of beta-adrenergic receptors during incubation with isoproterenol, the high-affinity non-beta-receptor binding sites are also deminishing during incubation with isoproterenol. Based on our findings it is concluded that the results of Henis et al. who claimed the visualization of the beta-adrenergic receptor population on Chang liver cells by alprenolol-NBD must be interpreted as an almost completely non-specific fluorescence.

4-Chloro-7-nitrobenzofurazan↗

PubMed1984

Low concentrations of potassium inhibit the Na-dependent [3H]glutamate binding to rat hippocampal membranes.

Potassium at low concentrations was found to inhibit the Na-dependent [3H]L-glutamate binding to rat hippocampal synaptic membranes. This inhibition was probably due to a competition between potassium and sodium at the ionic locus of the recognition site for glutamate of the uptake process. In addition, potassium inhibited the high-affinity [3H]L-glutamate uptake in hippocampal synaptosomes. These results provide an additional mechanism for the spreading of depression which accompanies seizure activity in the hippocampus.

Animals↗

PubMed1984

The esophagogastric polyp-fold complex.

A polyp-fold complex at the gastroesophageal junction is a rare finding. We made this diagnosis in a 51-year-old man who presented with abdominal discomfort after an episode of protracted vomiting. The esophagogastric polyp-fold complex is not always associated with reflux esophagitis, as was originally proposed.

Diagnosis, Differential↗

PubMed1983

Irreversibility and time course of calcium stimulated [3H]glutamate binding to rat hippocampal membranes.

Previous studies have indicated that calcium ions induce an irreversible increase of [3H]glutamate binding to rat hippocampal membranes. The present study was intended to provide an estimate of the time-course for this effect. The calcium chelator EGTA and the proteinase inhibitor leupeptin were introduced at various times during the incubation of hippocampal membranes with calcium and the binding of [3H]glutamate subsequently assayed. Both compounds totally blocked the calcium-induced increase in binding when added at the beginning of the incubation period but produced progressively less inhibition when added after longer delays. This method indicates that calcium produces its maximal effect between 5 and 10 min of incubation, a time-course compatible with the hypothesis that calcium stimulates a membrane-bound proteinase which results in the unmasking of [3H]glutamate binding sites.

Animals↗