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Biomedical subjects

E Friedman

Publications and source records attributed to E Friedman.

At least 397 records · Page 22Linked to original sources
PubMed1988

Chronic lithium: desensitization of autoreceptors mediating serotonin release.

The effect of chronic lithium treatment on K+-induced release of preloaded [3H] serotonin [( 3H]5-HT) from brain slices and its regulation by the presynaptic serotonin autoreceptors were investigated in superfused cortical, hippocampal and hypothalamic brain slices. Three weeks of treatment with a lithium-containing diet increased stimulation-induced [3H]5-HT overflow in the three brain regions examined. The sensitivity of the inhibitory serotonin autoreceptors was tested by determining K+-elicited release inhibition or potentiation in response to exposure to the agonist, LSD or to the antagonist, methiothepin, respectively. A reduced maximal inhibitory response to LSD was obtained in lithium-treated animals. The potentiation by methiothepin was also markedly diminished in the treated animals. These results suggest that chronic lithium treatment induces a desensitization of serotonin autoreceptors which may result in increased serotonin release from the serotonin nerve terminals.

Animals↗
PubMed1988

Differences in the cataleptogenic actions of SCH23390 and selected classical neuroleptics.

In an attempt to understand the nature of the interactions between D1 and D2 dopamine subsystems as well as between dopamine and acetylcholine, catalepsy was assessed in rats following various drug treatments. The D1-specific antagonist SCH23390 (0.1 mg/kg) produced prompt, potent and brief (less than 90 min) catalepsy with an ED50 of 0.105 mg (0.3 mumol)/kg. Conversely, fluphenazine (0.1 mg/kg), spiroperidol (0.1 mg/kg), and haloperidol (0.2 mg/kg) all had comparably potent but more slowly rising and prolonged (greater than 240 min) effects. The action of SCH23390 was synergistic with spiroperidol, inhibited by apomorphine or atropine, unaffected by mecamylamine, and markedly potentiated by pilocarpine. However, pilocarpine was unable to significantly potentiate the action of fluphenazine or spiroperidol. It is inferred that SCH23390 differs from the classical neuroleptics in its mechanism of cataleptogenicity, that there is a cholinergic link with the D1 dopamine system, and further, that there may be a difference in the nature or impact of the cholinergic interaction with the D1 and D2 dopamine systems.

Animals↗
PubMed1988

Merkel cell carcinoma arising in the oral mucosa.

This is the first reported case of a Merkel cell carcinoma arising in the oral mucosa. The tumor occurred in a 53-year-old white man, and it originated in the right mucobuccal fold. The Merkel cell origin was confirmed by electron microscopic and immunohistochemical studies.

Adenocarcinoma↗
PubMed1988

Effect of chronic lithium treatment on 5-hydroxytryptamine autoreceptors and release of 5-[3H]hydroxytryptamine from rat brain cortical, hippocampal, and hypothalamic slices.

The effect of acute and chronic lithium treatments on 5-hydroxytryptamine (5-HT, serotonin) release and on its regulation by presynaptic 5-HT autoreceptors was studied in [3H]5-HT preloaded superfused rat brain slices. The [3H]5-HT overflow evoked by a 30-s exposure to 65 mM K+ was increased after 3 weeks of ingestion of lithium-containing diet in the three brain areas examined. Acute injection of 4 mEq/kg lithium chloride did not affect 5-HT release. The K+-induced release observed in both control and chronically lithium-treated animals was Ca2+-dependent. Chronic lithium treatment was also found to be associated with a decrease in basal [3H]5-HT overflow in the cortex and hypothalamus but not in hippocampus [corrected]. The Ca2+-independent overflow induced by fenfluramine was also decreased in cortical slices from lithium-treated animals. The sensitivity of the inhibitory 5-HT autoreceptors was assessed by the response to the 5-HT agonist 5-methoxytryptamine. The results indicate a marked reduction in the maximal inhibition of [3H]5-HT release induced by 5-methoxytryptamine in slices obtained from animals which have been treated with lithium for 3 weeks. These data suggest that the functional down regulation of the prejunctional 5-HT sites may be responsible for the increase in K+-stimulated 5-HT overflow in brain slices of animals treated chronically with lithium.

5-Methoxytryptamine↗
PubMed1988

It couldn't happen. Health care? Airlines? Competition? Deregulation? Let's just put the whole thing together.

There are some almost-eerie parallels in how government, payers and patients/passengers view U.S. health care and U.S. air travel. Many claim to see the benefits of competition while some (even simultaneously) point to a need for regulation. The federal government in particular has supplemented traditional controls with "regulation by embarrassment," publishing on-time performance records for airlines and mortality rates for hospitals. Emily Friedman, writing from the imagined viewpoint of November 1994, thinks the parallels may be even eerier than many people realize.

Facility Regulation and Control↗
PubMed1987

Immunologic dysregulation in a patient with familial hemophagocytic lymphohistiocytosis.

A 6-year-old Jewish Iranian girl with familial hemophagocytic lymphohistiocytosis (FHLH) is described. The course of the disease fluctuated with partial initial response to antibiotics, steroids, and supportive treatment. Subsequent cytotoxic treatment, including VP-16, Velban (vinblastine sulfate), and methotrexate (MTX) controlled the disease for a few months but the child died with a clinical picture of meningocephalitis 1.5 years later. Benign-looking lymphohistiocytic infiltrates with varying degrees of hemophagocytosis were present in the bone marrow, pleural effusion, cerebrospinal fluid (CSF), liver, and brain. Clinical and laboratory evidence of immunologic dysregulation during the disease could be demonstrated. Frequent and intense viral and bacterial infectious diseases were encountered. The laboratory examination most consistently found was the absence of natural killer (NK) cell activity against K562 target cells. The impaired activity of NK cells persisted during all stages of the disease including remission, although NK cell numbers, determined morphologically and immunophenotypically (by Leu-11, Leu-7), were normal. Natural killer activity could not be restored by interferon. Moreover, the interferon system appeared to be intact. Impaired monokin interleukin 1 (IL-I) production by peripheral blood monocytes was found and could not be restored by indomethacin. Lymphopenia, a mild decrease in T4 numbers, and subsequently, decreased proliferative response to mitogens was noted. Elevated immunoglobulin levels were found during exacerbations and viral episodes, at times accompanied by the presence of auto-antibodies. The exaggerated fatal lymphohistiocytic response typical for FHLH could be attributed to a underlying genetic pathologic dysregulation of the various immunological response pathways.

Child↗
PubMed1987

Protein kinase C: regulation of serotonin release from rat brain cortical slices.

The effects of phorbol esters on serotonin release were examined in an attempt to investigate the role of protein kinase C in the regulation of serotonin release. Rat brain parietal cortical slices were incubated with [3H]5-HT in the presence of pargyline in order to label the serotonin stores. Potassium stimulated (30 s) release and spontaneous [3H]5-HT efflux were examined in slices during superfusion with Krebs-Ringer solution containing chlorimipramine. Repeated K+ stimulations elicited reproducible responses with release ratios of approximately 1.0. Introduction of phorbol 12-myristate, 13-acetate (PMA) or phorbol 12,13-dibutyrate (PDBu) 20 min prior to S2, or S3 resulted in dose-related increases in [3H]5-HT or [3H]NE release. PMA was slightly more potent (93% increase) than PDBu in potentiating K+-stimulated [3H]5-HT release. Phorbol and 4 alpha-phorbol 12,13-didecanoate (4 alpha PDD) which do not activate protein kinase C did not alter serotonin release. In contrast, basal [3H]5-HT and [3H]NE release were altered to a far lesser extent which was not always dose related. The response to the phorbol esters was reversible, Ca2+-dependent and reached maximal effect after 20 min of superfusion. The putative protein kinase C inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7) inhibited K+-induced [3H]5-HT release significantly (11%) but did not alter basal efflux. The PMA facilitation of serotonin release was, however, markedly prevented by the enzyme inhibitor. The effect of PMA on release was found not to be directly mediated through the prejunctional serotonin autoreceptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

The invasive adenylate cyclase of Bordetella pertussis. Properties and penetration kinetics.

Bordetella pertussis, the causative organism of whooping cough, produces a calmodulin-sensitive adenylate cyclase. Confer & Eaton [(1982) Science 217, 948-950] have shown that an extract from B. pertussis increases intracellular cyclic AMP levels in neutrophils and suggested that this increase is caused by the bacterial adenylate cyclase which penetrates these cells. We demonstrate in the present study that adenylate cyclase activity in lysates from lymphocytes exposed to a partially purified preparation of the bacterial enzyme has properties completely different from those of the intrinsic membrane-bound enzyme. Adenylate cyclase activity in lysates from lymphocytes exposed to the invasive enzyme is insensitive to N-ethylmaleimide, readily inactivated by acetic anhydride and relatively stable to SDS. Similar properties are exhibited by the bacterial enzyme itself. By contrast, the intrinsic membrane-bound enzyme activated by forskolin and guanosine 5'-gamma-thiotriphosphate is sensitive to N-ethylmaleimide and SDS and relatively stable to acetic anhydride. This strongly supports the notion that B. pertussis adenylate cyclase penetrates cells. Using the partially purified preparation of the invasive enzyme, we have studied the kinetics of its penetration. The intracellular catalytic activity reaches a steady state within 20 min, irrespective of enzyme or cell concentration. Steady-state levels are maintained for at least 2 h provided that the invasive enzyme is present in the incubation medium. Upon its removal, a rapid decrease (t1/2 approximately equal to 15 min) in the intracellular cyclase level is observed. This decrease reflects intracellular inactivation of the bacterial enzyme and is not caused by the release of the enzyme to the cell medium.

Adenylyl Cyclases↗
PubMed1987

The invasive adenylate cyclase of Bordetella pertussis. Intracellular localization and kinetics of penetration into various cells.

The penetration of Bordetella pertussis adenylate cyclase into various mammalian cells exhibits similar kinetics; the accumulation of both intracellular cyclase activity and cyclic AMP is rapid, reaching constant levels after 15-60 min of incubation. The kinetics of enzyme penetration into turkey erythrocytes is different; cyclase activity and cyclic AMP accumulate linearly and do not reach constant levels even after 6 h of incubation. In the preceding paper [Friedman, Farfel & Hanski (1987) Biochem. J. 243, 145-151] we have suggested that the constant level of intracellular cyclase activity reflects a steady state formed by continuous penetration and intracellular inactivation of the enzyme. In contrast with other mammalian cells, no inactivation of cyclase is observed in turkey erythrocytes. These results further support the notion that there is continuous penetration and deactivation of the invasive enzyme in mammalian cells. A 5-6-fold increase in specific activity of the invasive cyclase is detected in a pellet fraction of human lymphocytes in which a similar increase in specific activity of the plasma-membrane marker 5'-nucleotidase is observed. A similar increase in the invasive-cyclase specific activity is detected in a membrane fraction of human erythrocytes. Cyclase activity in a membrane-enriched fraction of human lymphocytes reached a constant level after 20 min of cell exposure to the enzyme. Similar time courses were observed for accumulation of cyclase activity and cyclic AMP in whole lymphocytes [Friedman, Farfel & Hanski (1987) Biochem, J. 243, 145-151]. We suggest therefore that cyclic AMP generation by the invasive enzyme as well as the intracellular inactivation process occur while it is associated with a membrane fraction identical, or closely associated, with the plasma membrane.

Adenylyl Cyclases↗