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Biomedical subjects

S Steiner

Publications and source records attributed to S Steiner.

At least 73 records · Page 4Linked to original sources
PubMed1991

Mouse skin inflammation induced by multiple topical applications of 12-O-tetradecanoylphorbol-13-acetate.

It is well known that applications of a single dose of 12-O-tetradecanoylphorbol-13-acetate (TPA) to mouse ears induces an acute inflammatory reaction consisting of erythema, edema and polymorphonuclear leukocyte (PMN) infiltration. We report here that multiple topical applications of TPA to mouse ears produce a prolonged inflammatory reaction characterized by increases in ear weight, inflammatory cell infiltration and epidermal hyperplasia. TPA was applied 5 times over 10 days to mouse ears. Epidermal thickness and PMN infiltration (myeloperoxidase content) increased 3- and 160-fold, respectively, by day 3 and remained elevated over control values throughout the test period. Ear weight was elevated from day 1 and remained high. Hydrocortisone 17-valerate and betamethasone dipropionate significantly reduced all three parameters of inflammation. Indomethacin and two other cyclo-oxygenase inhibitors, and an antihistamine had little or no effect on any of the parameters. This chronic skin inflammation model may be more relevant for evaluating anti-inflammatory compounds than the acute TPA model because the test compounds are applied after the inflammatory lesion is established, which mirrors the use of clinical anti-inflammatory drugs. Also this model may be more selective than the acute TPA model for compounds which affect leukotriene production since other pharmacological agents which are active in the acute model are not active in the multiple-application model.

Administration, Topical↗
PubMed1988

The role of fatty acid metabolites in the differentiation of the human monocyte-like cell line U937.

The human monocyte cell line, U937, can be induced to terminally differentiate into macrophage-like cells when treated with gamma-interferon. However, if these cells were treated with gamma-interferon and esculetin, an inhibitor of the lipoxygenase pathway, or BW755C, an inhibitor of both the lipoxygenase and the cyclooxygenase pathways, a marked inhibition in cellular differentiation occurred. In contrast, inhibitors of only the cyclooxygenase pathway had no effect on differentiation. These studies suggest a role for lipoxygenase products of arachidonic acid in the differentiation of the human U937 cell line. Arachidonic acid utilized in the production of eicosanoids is derived from phospholipids by the action of phospholipase A2 and phospholipase C. When U937 cells were cultured in medium supplemented with gamma-interferon, there was a striking increase in the level of phosphatidylcholine and phosphatidylethanolamine-specific phospholipase A2 activities and phosphatidylinositol-specific phospholipase C activity as compared to control cells. More ever, although there was not a significant difference in the incorporation of labeled arachidonic acid or linoleic acid into the major phospholipids of differentiated U937 cells as compared to undifferentiated control cells, there was a marked increase in the relative amount of the labeled arachidonic acid released from the differentiated cells as lipoxygenase products compared to cyclooxygenase products. These data suggest that lipoxygenase products may be essential in the differentiation process of U937 cells and that enhanced phospholipase enzyme activities that occur during differentiation help explain how arachidonic acid becomes available to form lipoxygenase products.

Cell Differentiation↗
PubMed1986

Leukotriene D4 treatment of bovine aortic endothelial cells and murine smooth muscle cells in culture results in an increase in phospholipase A2 activity.

Leukotriene D4 stimulates prostanoid synthesis in smooth muscle and endothelial cells. Because phospholipases A2 and C have been proposed to regulate prostanoid synthesis, we examined the effect of leukotriene D4 on these activities. Leukotriene D4 treatment resulted in a dose-dependent, stereospecific increase in phospholipase A2 activity with phosphatidylcholine as a substrate. The induction of phospholipase A2 activity occurred just prior to the appearance of prostanoids in the media. Protein and RNA synthesis were required for the increase in phospholipase A2 activity, and the increase in activity resulted from an increase in the apparent Vmax of the phospholipase A2 enzyme. Phospholipase C activity using various substrates was unchanged. We conclude that the increase in prostanoid synthesis observed after leukotriene D4 treatment is a result of an increase in a phospholipase A2 activity.

Animals↗
PubMed1986

Optimizing glycemic control: can insulin dependent diabetic patients rely on their perception of blood glucose fluctuations in order to make therapeutic decisions?

30 insulin dependent diabetic (IDD) patients without clinically evident autonomic neuropathy were asked on 128 occasions to estimate quantitatively what they believed their capillary blood glucose (CBG) to be (predicted blood glucose--PBG) immediately before an actual CBG measurement was performed (real blood glucose--RBG). A statistically significant correlation was found between the pooled RBG's and PBG's of our patient population (r = 0.57, p less than 0.001). However, there was a notable skewing of the RBG/PBG curve, evidencing a tendency of our patients' predictions to be closer to normality. This is further documented by the fact that the mean M value of the RBG's of each of the 11 patients with more than 6 predictions was significantly greater than the mean M value of the corresponding PBG's. Within the ranges of hypoglycemia (RBG less than or equal to 3.3 mmol/l) and of normoglycemia (3.4-7.8 mmol/l) there was no correlation between RBG's and PBG's. With RBG's greater than or equal to 7.8 mmol/l the correlation was statistically significant (r = 0.41, p less than 0.01). When the pooled predictions were analyzed according to qualitative accuracy for different ranges of RBG the following trend emerges: for RBG's less than or equal to 3.3 mmol/l (60 mg%), 2/11 predictions were accurate (18%), for RBG's greater than or equal to 12.3 mmol/l (221 mg%), 30/37 (81%) and for RBG's between 3.4 and 12.2 mmol/l (61-220 mg%), 44/80 (55%). In conclusion, our patients as a whole showed an ability to discriminate between high, normal and low levels of blood glucose, albeit with a strong bias to predict values closer to the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1984

Effect of inhibitors of the lipoxygenase pathway on mouse myoblast fusion.

In this study we examined the effects of inhibitors of the lipoxygenase and cyclooxygenase pathways on mouse myoblast fusion. The fusion of cloned mouse myoblasts was markedly inhibited, in a dose-dependent manner, when cells were cultured in medium supplemented with either phenidone (1-phenyl-3-pyrazolidione) or BW755c (3-amino-1-(3-tri-fluoromethylphenyl)-2-pyrazoline), drugs which have been reported to inhibit lipoxygenase and cyclo-oxygenase activities. Fusion was also inhibited when these cells were cultured in medium supplemented with esculetin (6,7-dihydroxycoumarin) which has been reported to inhibit lipoxygenase activity. Removal of the above inhibitors resulted in a return to control levels of fusion. Fusion was not demonstrably inhibited with aspirin (acetylsalicylic acid) and only inhibited to a minor extent with indomethacin (1-(p-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetic acid); both of these drugs are inhibitors of cyclo-exygenase activity.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1983

The effect of rapid eye movement sleep deprivation on cortical beta-adrenergic receptors.

The relationship between rapid eye movement sleep deprivation (REMD) and rat beta-adrenergic receptors was evaluated. REMD was achieved using the platform method and verified by EEG and EMG recordings. Although the amount of REM sleep was diminished 90%, there was no alteration in either the number of binding sites or their affinity for [3H]-dihydroalprenolol. Periods of stress as well as recovery periods after REMD were also without effect on the cortical beta-adrenergic receptors. Thus no support is garnered for the interaction of REMD and the cortical beta-adrenergic receptor binding parameters, although REMD is sometimes used as a mode of therapy for depression and other antidepressives do in fact affect the beta-adrenergic system. The mechanism of REMD as a potential antidepressive therapy is yet to be elucidated.

Animals↗
PubMed1983

Trapping of the beta-adrenergic receptor in the hormone-induced state.

Isoproterenol and other agonists readily dissociate from the beta-adrenergic receptor in turkey erythrocyte membranes. However, when a low concentration of deoxycholate is added, the receptor locks the prebound agonist; i.e., the rate of dissociation of the prebound agonist decreases drastically. The dissociation of prebound antagonists is slightly increased by deoxycholate. Locking, which is thus agonist specific, occurs in the cold, is reversed when detergent is removed from the membranes, and appears not to require the guanyl nucleotide binding protein of the adenylate cyclase system. It is suggested that this induced fit of a receptor to an agonist represents the specific conformational response that normally propagates in the receptor molecule in its interaction with the next component along the pathway of signal transmission.

Animals↗
PubMed1981

Follow-up study of 281 schizophrenic patients treated with high dosage fluphenazine decanoate.

281 newly admitted female schizophrenic patients were treated with high dosage fluphenazine decanoate intramuscularly, starting with 250 mg per injection together with antiparkinsonian and antidepressant drugs. On a set day the 3 groups 'with neuroleptics' (NL) (n = 54), 'without NL' (n = 152) and 'relapsed when without NL' (n = 42) were compared concerning age, diagnosis, hereditary disposition, first admission and readmissions, number of admissions and global judgement. From the differences no clear conclusion for practical clinical work could be obtained. The good tolerance is discussed using the list of side effects including tardive dyskinesia and laboratory data.

Age Factors↗
PubMed1980

Effects of sodium butyrate on the membrane glycoconjugates of murine sarcoma virus-transformed rat cells.

The temporal relationship between butyrate-induced cellular flattening of murine sarcoma virus-transformed rat cells (MSV-NRK) and alterations in certain surface-associated biochemical markers of transformation, e.g., surface glycopeptides, glycolipids, fibronectin, hexose uptake, and cell-substrate adhesion was examined. The induction of elevated levels of the ganglioside GM3 and of a GDla-like ganglioside were observed to precede or to parallel cellular flattening. Likewise, enhanced incorporation of radioisotopically labeled fucose into a novel fucose-containing component, i.e., glucopyranosyl (1 leads to 3) fucopyranosyl-threonine, was also observed to occur at an early stage of cellular flattening. In contrast, a shift in the molecular weight distribution of trypsin-sensitive, surface fucopeptides was observed to occur at a late stage of cellular flattening. Moreover, surface fibronectin was not detectable in the butyrate-flattened MSV-NRK cells despite the fact that the cells manifested significantly enhanced cell-substrate adhesion. Thus, butyrate appears to be a useful tool for understanding the sequential changes associated with expression of the transformed phenotype of MSV-NRK cells.

Animals↗
PubMed1980

[Modification of schizophrenia by intensive neuroleptic therapy and the course of the disease after withdrawal of neuroleptic drugs].

Since 1976 a group of 229 patients with schizophrenic or other paranoid illness (9 patients) were treated for about 14 weeks with intramuscular or intravenous injections of fluphenazinedecanoate. During the first 2 weeks, three injections of 250 mg were given after which time the injections were given at three weekly intervals with slowly decreasing dosage. The patients also received tablets of procyclidine and 100-150 mg of amitriptyline per os. After the initial intensive phase the patients received an average of 145 mg i.m. every 3 weeks. A total of 209 patients could be followed up. Of those, 127 had for various reasons not continued with oral medication. The course of their illnesses was compared with that of the patients who had complied. The present report which represents a 3-year follow-up study confirms the findings of an earlier paper which showed the rapid onset and stability of remission, the absence of relapses among the patients who were under continued treatment, and the relative freedom from relapses among the patients who did not continue to have further neuroleptic medication. The anticipation that the initial high-dosage medication would have deleterious effects on the personality, producing robots or zombies, was shown to be groundless.

Adolescent↗
PubMed1977

Cyclic AMP-induced morphological transformation of cells infected by temperature-sensitive mouse sarcoma virus. Expression of transformation-associated markers.

Normal rat kidney (NRK) cells infected with a temperature-sensitive (ts) mutant of mouse sarcoma virus (NRK [MSV-1b]) express the transformed phenotype when grown under permissive conditions, but acquire the normal phenotype when grown under restrictive conditions. Addition of 3', 5' cyclic adenosine monophosphate (cAMP) to NRK (MSV-1b) cells grown at the restrictive temperature results in morphological transformation. To determine whether other markers associated with the transformed phenotype were coordinately expressed after cAMP exposure, concanavalin A (Con A) agglutinability, hexose transport rate, and incorporation of radioactively labeled fucose into fucolipid III and fucolipid IV (FL III and FL IV ) of the cells were examined. NRK cells transformed by wild-type MSV or NRK(MSV- 1b) grown under permissive conditions were agglutinated by low concentrations of Con A and exhibited relatively high maximal agglutination levels which were specifically inhibited by alpha-methyl-D-mannoside. In contrast, NRK (MSV-1b) cells grown under restrictive conditions were weakly agglutinated by Con A and exhibited reduced maximal agglutination levels, similar to uninfected NRK cells. Treatment of NRK (MSV-1b) cells at the restrictive temperature with cAMP resulted in morphological transformation and a change in the pattern of incorporation of labeled fucose inot FL III and FL IV to one comparable to that of NRK (MSV-1b) cells at the permissive temperature or to NRK cells transformed by wild-type MSV. In contrast, cAMP treatment resulted in no increase in Con A agglutinability or 2 deoxy-D- [(3)H]glucose transport relative to mock treated cultures. The results demonstrate that cAMP-induced morphological transformation and altered fucolipid composition of NRK (MSV-1b) cells are not correlated with alterations in hexose transport rate or Con A agglutinability.

Agglutination↗