Search PubMed⌕ Search

Biomedical subjects

E Friedman

Publications and source records attributed to E Friedman.

At least 343 records · Page 19Linked to original sources
PubMed1990

Pre- and post-synaptic cholinergic dysfunction in aged rodent brain regions: new findings and an interpretative review.

Age-related impairment of dynamic aspects of central cholinergic neurotransmission has been indicated by many studies of aged rodents, but the regional distribution of cholinergic deficits and the relative contribution of presynaptic hypofunction and reduced acetylcholine release, loss of synaptic integrity or loss of muscarinic receptors remains unclear. This study therefore compared choline acetyltransferase activity (as a structural marker) and sodium-dependent high affinity choline uptake (which reflects both ongoing cholinergic neuronal activity and structural integrity) in the hippocampus, cortex and straitum of male C57BL mice at 3-4, 10-12 or 28-32 months of age. To evaluate the relationship of changes in muscarinic receptors to presynaptic alterations, binding of the antagonist 3H-quinuclidinyl benzilate was compared in membranes prepared from each of these brain regions. High affinity choline uptake was significantly reduced in all three brain regions by 28-32 months of age. This trend was already evident by 10-12 months of age, especially in hippocampus and cortex. By contrast, choline acetyltransferase activity was unchanged in striatum and actually increased in hippocampus and cortex of aged mice. Muscarinic binding was reduced significantly only in striatum and this effect was significant by 10-12 months of age. This decrease in antagonist binding was accompanied by a small but significant reduction in the relative proportion of high affinity agonist sites as defined by carbachol displacement. The impairment of high affinity choline uptake in the absence of a parallel reduction of choline acetyltransferase activity suggests a decline of ongoing cholinergic activity rather than loss of terminal integrity as the basis of presynaptic deficits in aging. This functional decline may be exacerbated by reduction of muscarinic receptors in striatum. Despite considerable literature support for the hypothesis that cholinergic mechanisms are impaired with age, several controversies leave important issues unresolved. Therefore, the present results are discussed in the context of a critical review with emphasis on dynamic properties of presynaptic function which require analysis in experimental animal models. The impact of normal aging on brain cholinergic systems is distinguished from the neurodegenerative changes in Alzheimer disease in that presynaptic function is compromised with a relative preservation of the integrity of innervation.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMed1990

Mutations of the Gs alpha-subunit gene in Albright hereditary osteodystrophy detected by denaturing gradient gel electrophoresis.

Affected members of most kindreds with Albright hereditary osteodystrophy have a partial deficiency of functional Gs, the guanine nucleotide-binding protein that stimulates adenylyl cyclase. By use of the polymerase chain reaction to amplify genomic fragments with the attachment of a high-melting G + C-rich region (GC clamp) and analysis of these fragments by denaturing gradient gel electrophoresis, heterozygous mutations in the Gs alpha-subunit gene were found in two kindreds. These included a G----C substitution at the donor splice junction of intron 10 and a coding frameshift created by a single base deletion within exon 10. The findings illustrate the heterogeneity of genetic defects in Albright hereditary osteodystrophy and the usefulness of the polymerase chain reaction-denaturing gradient gel electrophoresis method to search rapidly for mutations in a large candidate gene.

Amino Acid Sequence↗
PubMed1990

Acute dystonia during fixed-dose neuroleptic treatment.

Eighty-six patients with acute psychotic exacerbations were treated with fixed dosage regimens of oral fluphenazine up to 10-30 mg/day in randomized, double-blind studies. Dystonic reactions occurred in 33.8% of the subjects at risk. Of these, 58% occurred by the third day, 88% by the fourth day, and 100% by the ninth day of treatment; most occurred later in the interdose interval. Significant predictors of dystonic reactions were higher fluphenazine mg/kg dosage and younger age. There was a trend toward a lower risk of dystonia in patients who received amobarbital sodium for agitation. Results are discussed in relation to possible mechanisms of neuroleptic-induced dystonia.

Adult↗
PubMed1990

Genetic abnormalities in sporadic parathyroid adenomas.

We analyzed genomic DNA from 43 sporadic benign parathyroid adenomas for rearrangements of the PTH gene, and for point mutations of the H-ras (codons 12, 13, and 61), N-ras (codons 12, 13, and 61), and K-ras (codons 12 and 13) genes. One of 43 parathyroid adenomas showed a chromosome 11 rearrangement involving both the PTH gene on the short arm of chromosome 11 (at band p15) and a locus on the long arm (11q13). This rearrangement was indistinguishable from one that was previously described in a parathyroid adenoma by Arnold et al., indicating that this may be an important contributor to tumorigenesis in a small subset of patients with parathyroid adenoma. H-ras, K-ras, and N-ras oncogene activation by point mutation at codons 12, 13, or 61, known to occur in many tumors, could not be detected in any parathyroid adenoma.

Adenoma↗
PubMed1990

To save and to let go.

Recognizing what's right with the U.S. health-care system is as helpful in shaping reform as pointing out what's wrong.

Delivery of Health Care↗
PubMed1990

Stimulation of a dopamine D1 receptor enhances inositol phosphates formation in rat brain.

Accumulation of inositol phosphates was determined in rat brain slices prelabeled with 2-[3H]inositol and incubated with various drugs. In the striatum, micromolar concentrations of dopamine, apomorphine and SKF38393 induced significant accumulations of inositol phosphates in a dose-dependent manner, whereas quinpirole lacked effect. The EC50 values for the accumulation of inositol monophosphate induced by dopamine, apomorphine and SKF38393 were, respectively, 148, 159 and 129 microM. SKF 38393 effect was time-dependent on the accumulation of all three inositol phosphates, with peak effects occurring 64-128 min after drug addition. The action of the dopamine D1 receptor agonist, SKF38393, was blocked by SCH23390 (D1-selective antagonist), but not by sulpiride (D2-selective antagonist), atropine (muscarinic antagonist), prazosin (alpha-1 adrenoceptor antagonist) or methiotepin and methysergide (serotonergic antagonists), indicating that the observed effects of dopaminergic agonists were selectively mediated through the D1 dopamine receptor. On examining the effect of SKF38393 in several brain regions, the highest dopaminergic stimulation of inositol phosphates formation was obtained in the amygdala, followed by the hippocampus and then the striatum and frontal cortex. The finding of an SKF38393-stimulated PI hydrolysis in amygdala, a brain region that is enriched in SCH23390 and SKF38393 binding sites but devoid of dopamine-stimulated adenylate cyclase, suggests that the D1 receptor that is linked to PI metabolism is independent of the D1 receptor which stimulates cyclic AMP formation.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1990

Growth of tracheal anastomoses in lambs. Comparison of PDS and Vicryl suture material and interrupted and continuous techniques.

Tracheal anastomoses were performed in 19 lambs (mean age 4 weeks, mean weight 9.8 kg) to compare polydioxanone (PDS) and polyglactin 910 (Vicryl) suture material (Ethicon, Inc., Somerville, N.J.) and simple continuous and simple interrupted suture technique. Each animal had two anastomoses with full-thickness bites for both suture techniques. Animals were killed at 4 months (n = 6) or 8 months (n = 5). Eight animals died before they were scheduled to be put to death (mean 6 weeks postoperatively). Transverse sections of the trachea were taken at the level of the anastomoses and three tracheal rings above and below each anastomosis. The cross-sectional area of the tracheal lumen of these transverse sections was measured with a computerized digitizing tablet. A percent luminal area for each anastomosis was calculated relative to the mean tracheal area three rings above and three rings below the anastomosis. There was little difference between interrupted and continuous technique with either suture material (p = 0.94). In 10 animals that each served as its own control for suture material, PDS anastomotic area was 55.0% +/- 4.1% of mean tracheal luminal area compared with 45.4% +/- 7.1% for Vicryl anastomoses (p = 0.06). Histologic analysis revealed a more intense inflammatory reaction surrounding multifilament Vicryl sutures with more rapid resorption and greater subsequent fibrosis relative to the reaction seen with PDS sutures. A small clinical experience with seven infants has confirmed short-term satisfactory clinical performance of continuous PDS suture for tracheal anastomosis.

Anastomosis, Surgical↗
PubMed1990

Transforming growth factor beta 1 acts as an autocrine-negative growth regulator in colon enterocytic differentiation but not in goblet cell maturation.

Previous studies from this laboratory (Schroy, P., Rifkin, J., Coffey, R.J., Winawer, S., and Friedman, E. (Cancer Res., 50: 261-265, 1990; Schroy, P.C., Winawer, S., and Friedman, E. Cancer Lett., 48: 53-58, 1989) found that a 7-day treatment of the human colon carcinoma cell line HT29 with the differentiation agent hexamethylene bisacetamide (HMBA) induces both a 4-5-fold increase in transforming growth factor beta 1 (TGF beta 1) mRNA levels and reduced tumorigenicity in vivo. A series of 15 cloned lines with different commitments to differentiation has been isolated from 20-day HMBA-treated HT29 cells, maintained without HMBA, and utilized to study the role of TGF beta 1 in colon carcinoma differentiation. Two such lines, HD6 and HD8, differentiate to 97 and 76% mucus-secreting goblet cells, respectively, in columnar monolayers in postconfluent culture. Both HD6 and HD8 cells exhibit low TGF beta 1 mRNA levels, little different from the undifferentiated HT29 parental line, and exhibit no growth modulation in response to exogenous TGF beta 1. In contrast, two other lines, HD3 and HD4, differentiate to fluid-transporting enterocytic cells with functional brush borders and exhibit autocrine-negative growth response to TGF beta 1. Both lines express TGF beta 1 mRNA at levels 11-12-fold higher than the parental line and respond to exogenous TGF beta 1 by growth inhibition. HD3 cells secrete biologically active TGF beta 1 into conditioned media, which inhibited growth of a TGF beta 1-sensitive mink cell line. This inhibition was blocked by antisera to TGF beta 1, proving the specificity of the inhibition. A range of concentrations of this TGF beta 1 antiserum stimulated HD3 cell growth in a dose-dependent manner, further documenting the autocrine-negative response of the cells to TGF beta 1. Another cell line, HI1, was blocked in enterocytic differentiation. HI1 cells synthesized as much TGF beta 1 mRNA as HD3 and HD4 cells, yet they responded to exogenous TGF beta 1 with less growth inhibition, suggesting some impairment in their response to TGF beta 1. A third class of response to TGF beta 1 was exhibited by the HP1 cell line, which was resistant to HMBA-induced differentiation, remaining undifferentiated with a multilayered growth pattern. HP1 cells synthesized TGF beta 1 mRNA at levels over 20 times the parental level but were stimulated to divide by TGF beta 1, exhibiting autocrine-positive response to this growth factor.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetamides↗
PubMed1990

Central 5-hydroxytryptamine receptor-linked protein kinase C translocation: a functional postsynaptic signal transduction system.

The effect of 5-hydroxytryptamine (5-HT) receptor stimulation on protein kinase C (PKC) activity and translocation was assessed in slices or synaptosomes obtained from rat brain. Serotonin (0.5-100 microM) and the specific 5-HT2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (0.01-10 microM) but not the 5-HT1A or 5-HT1B agonists elicited time- and dose-related translocations in cortical slices. The maximal translocation elicited by 5-HT (10-100 microM, 15 min) or DOI (1 microM, 10 min) was similar to that achievable by the phorbol ester phorbol myristate acetate (PMA) (162 nM). In synaptosomes, short exposures to depolarizing concentrations of K+ (45-65 mM) resulted in PKC translocation. In addition, PMA but not serotonin induced enzyme translocation in synaptosomes. In slices, serotonin-stimulated PKC translocation was prevented by 5-HT2 antagonists but not by dopamine or alpha-adrenergic antagonists. PKC translocation induced by serotonin but not by PMA was inhibited by incubation of slices in a Ca2+-free medium. However, addition of 0.5 mM ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid to the incubation mixture abolished the effects of both serotonin and PMA. These results indicate that, in cortical slices, serotonin operating via a 5-HT2 postsynaptic receptor can induce the translocation of PKC from cytosol to membrane. This action of the neurotransmitter appears to be dependent on extracellular Ca2+.

Animals↗
PubMed1989

Effect on in vivo tumorigenicity of lengthy exposure of human colon cancer cells to the differentiation agent hexamethylene bisacetamide.

The heterogeneity of tumor responses to maturation agents was studied using the multi-potential, non-cloned human colon carcinoma cell line HT29. Short-term treatment (5 cell doublings) with the differentiation agent hexamethylene bisacetamide (HMBA) induced a sharp decrease in tumorigenicity in vivo and loss of a cell surface malignancy marker. However, prolonged treatment (22 cell doublings) with the agent lead to loss of the HMBA-sensitive subpopulation from the mass culture, and enrichment of a tumorigenic, HMBA-resistant subpopulation.

Acetamides↗