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Biomedical subjects

C Stein

Publications and source records attributed to C Stein.

At least 127 records · Page 7Linked to original sources
PubMed1991

Peripheral analgesic actions of opioids.

This paper will review experimental and clinical studies investigating analgesic effects of opioids outside the central nervous system. The experimental data indicate that 1) opioids can produce antinociceptive effects in the periphery mediated by local opioid receptors, 2) three different receptor types (mu, delta, kappa) can become active in peripheral tissue, 3) inflammatory hyperalgesic conditions are especially amenable to peripheral opioid actions and 4) the activation of opioid receptors located on primary afferent neurons is the most likely mechanism of action. The evidence from clinical studies is equivocal so far, partly because of methodological shortcomings. More extensive controlled studies investigating the effects of local application of opioids in the vicinity of peripheral nerve terminals or of compounds unable to cross the blood-brain barrier are warranted in view of the potential avoidance of central side effects such as respiratory depression, dependence, nausea or sedation.

Animals↗
PubMed1991

[Extracorporeal lithotripsy of urinary calculi: experience with Modulith SL-20 (Storz Medical)].

The results of extracorporeal lithotripsy on 250 patients with renal and ureteral stones are reported. Stone size varied from less than 1 cm (64%), 1 to 2 cm (31%) to over 2 cm (4%). 51% of patients were treated on an ambulatory basis. Complete fragmentation was obtained in 97% of patients and 78% were free of any demonstrable stone after 90 days. lithotripsy is an effective procedure allowing ambulatory non surgical treatment of urinary stones in many patients.

Adolescent↗
PubMed1990

Antisense-mediated inhibition of BCL2 protooncogene expression and leukemic cell growth and survival: comparisons of phosphodiester and phosphorothioate oligodeoxynucleotides.

Antisense oligodeoxynucleotides specific for sequences in mRNAs from the B-cell lymphoma/leukemia-2 (BCL2) gene were used to inhibit the growth in culture of a human leukemia cell line, 697. Normal phosphodiester (PO) and nuclease-resistant phosphorothioate (PS) oligodeoxynucleotides were compared with regard to specificity, potency, and kinetics. Both PO and PS antisense BCL2 oligodeoxynucleotides were specific inhibitors of cellular proliferation, since sense versions of these synthetic DNAs were inactive at similar concentrations. Specificity was further confirmed by quantitative immunofluorescence studies, showing that PO and PS antisense BCL2 oligodeoxynucleotides (when used at appropriate concentrations) reduced levels of BCL2 protein without influencing expression of HLA-DR and other control antigens. The onset of inhibition by PO oligodeoxynucleotides was faster, with reductions in cell numbers occurring within 1 day of addition to cultures, in contrast to phosphorothioates, which were ineffective until 3-4 days. Phosphorothioates were more potent that phosphodiesters, however, with half-maximal inhibition of leukemic cell growth occurring at concentrations 5-10 times lower. As expected from previous studies demonstrating the importance of BCL2 for regulating lymphoid cell survival, BCL2 antisense oligodeoxynucleotides also led to 697 leukemic cell death through sequence-specific mechanisms, with reductions in cellular viability generally lagging the inhibitory effects on cellular growth by about 2 days. Taken together, these data indicate that PO and PS oligodeoxynucleotides targeted against the human BCL2 protooncogene can be sequence-specific inhibitors of leukemic cell growth and survival.

Cell Division↗
PubMed1990

Involvement of capsaicin-sensitive neurones in hyperalgesia and enhanced opioid antinociception in inflammation.

The effects of capsaicin pretreatment of adult rats was investigated on consequences of unilateral paw inflammation induced by inoculation with Freund's adjuvant. Decrease in mechanical nociceptive threshold in the inflamed paw, as measured by the paw pressure test, was dose-dependently inhibited by capsaicin (20-150 mg/kg s.c.). In control rats, the antinociceptive action of morphine (0.8-1.9 mg/kg s.c.) was greater in the inflamed than in the non-inflamed paw; this difference was absent in capsaicin-treated animals. Increased volume or skin temperature of the inflamed paw was not influenced by capsaicin. It is concluded that capsaicin-sensitive, presumably C-fibre neurones, but not an alteration of the inflammation itself by capsaicin, mediate hyperalgesia and increased morphine antinociception in the rat paw with adjuvant-induced inflammation.

Analgesics↗
PubMed1990

Rats with dorsal hippocampal lesions do react to new stimuli but not to spatial changes of known stimuli.

The effect of visual distracting stimuli upon the straight alleyway performance of dorsal hippocampectomized Wistar rats was investigated. In comparison with control animals it was observed that dorsal hippocampectomized animals (1) ambulated more during the preexposure phase, (2) acquired at the same rate a running response for food (training phase), (3) reacted similarly to a new visual stimulus (black cards) presented in a sector of the alleyway, and (4) habituated to successive presentations of that stimulus in the same place. (5) However, dorsal hippocampectomized rats did not react, unlike the controls, to the presentation of the same stimulus in another place of the alleyway but (6) reacted to the visual pattern change of the stimulus (now black/white check cards) in the same place. These results indicate that under certain experimental conditions, hippocampus-lesioned animals are capable of interrupting a running response for food in order to explore a new conspicuously located stimulus, habituate to repeated presentations of that stimulus, and to react to a new pattern of visual stimulation. They suggest that hippocampectomized rats do not lose the capacity to react to a new stimulus; the disruption seems to be related to the spatial context of stimulus presentation, supporting a spatial mapping hypothesis of hippocampal function.

Animals↗
PubMed1990

Opioids from immunocytes interact with receptors on sensory nerves to inhibit nociception in inflammation.

Exogenous opioids can produce localized opioid receptor-mediated antinociception in peripheral inflamed tissue. Previous studies show that activation of endogenous opioids by a cold water swim in rats with hind paw inflammation results in a similar local antinociceptive effect but suggest that pituitary-adrenal opioid pools are not directly involved in producing this effect. Here we show increased amounts of opioid peptides in immune cells infiltrating the inflamed tissue. Furthermore, we demonstrate immunoreactive opioid receptors on peripheral terminals of sensory neurons. The local administration of antibodies against opioid peptides or receptors or systemic pretreatment with the immunosuppressant cyclosporine blocks cold water swim-induced antinociception. These findings suggest that antinociception in inflammation can be brought about by endogenous opioids from immune cells interacting with opioid receptors on peripheral sensory nerves.

Animals↗
PubMed1990

A test of fine finger dexterity.

The lack of instruments available for the measurement of fine dexterity (i.e., speed of interdigital manipulation) implies a gap not only in the occupational therapist's ability to quantify and deal precisely with patients' problems in this area, but also in the knowledge base of occupational therapy itself. The Rosenbusch Test of Finger Dexterity (developed by Doris F. Rosenbusch, MA, OTR), a new instrument that measures the speed of interdigital manipulation of objects by each hand separately, was tested on 64 subjects with normal hand function and 10 subjects known to have disabilities affecting fine dexterity. The determination of significant differences by the subjects' sex, dominant and nondominant hands, and normal and dysfunctional hands was performed with t tests. The scores of the subjects with normal hand function versus those with disabled hand function were then compared on all variables. The findings demonstrate that this instrument is ready to be used experimentally and compares favorably with current commercial tests on both reliability and validity coefficients.

Adult↗
PubMed1990

Intrinsic mechanisms of antinociception in inflammation: local opioid receptors and beta-endorphin.

This study examined antinociception induced through the activation of local opioid receptors in inflammation by endogenous opioids. Rats developed a unilateral localized inflammation upon injection of Freund's adjuvant into one hindpaw. Four to 6 d later they were subjected to cold water swim (CWS), an environmental stimulus known to activate intrinsic opioid systems. Following CWS (1 min) the animals' withdrawal threshold to noxious pressure applied onto the paws increased significantly more on the inflamed paw than on the noninflamed paw. This unilateral antinociceptive effect in inflamed paws was dose-dependently and stereospecifically reversible by intraplantar (i.pl.) but not systemic (i.v. or s.c.) administration of the opioid antagonist naloxone (18 micrograms). This suggested that CWS-induced antinociception in inflamed tissue was brought about by the activation of local opioid receptors. Antiinflammatory or vasoconstrictive events, as measured by paw volume and temperature, did not contribute to this unilateral antinociception. Receptor-selective antagonists indicated the involvement of mu- and delta- but not kappa-receptors. Intravenous application of a universal antibody to endogenous opioid peptides (3-E7) and a specific antibody to beta-endorphin, but not antisera against metenkephalin or dynorphin, abolished the CWS effect. Finally, the i.pl. injection of synthetic beta-endorphin (1-31) produced an antinociceptive effect in inflamed paws which was reversible by i.pl. naloxone and selective mu- and delta-receptor antagonists. These findings suggest that antinociception in inflamed tissue can be induced through the activation of local opioid receptors by endogenous beta-endorphin released during CWS.

Animals↗
PubMed1989

Cloning and expression of human steroid-sulfatase. Membrane topology, glycosylation, and subcellular distribution in BHK-21 cells.

A 2.4-kilobase cDNA clone for human steroid-sulfatase (STS) was isolated and sequenced, which encoded an enzymatically active protein. The deduced amino acid sequence comprises 583 amino acids with an N-terminal signal peptide of 21 or 23 residues and four potential N-glycosylation sites. Two of the N-glycosylation sites are utilized and were localized to the asparagine residues 47 and 259. STS has the solubility properties of an integral membrane protein. The resistance of STS toward proteinase K after translocation into microsomes suggests that most, if not all, sequences of STS are exposed at the luminal side of microsomes. The deduced amino acid sequence predicts two membrane-spanning domains (amino acids 185-211 and 213-237) separated by a helix-breaking proline residue. We propose for STS a three-domain model. Two glycosylated luminally oriented domains of 161 and 346 residues are separated by a hydrophobic domain spanning the membrane twice in opposite directions. STS expressed in BHK-21 cells is located predominantly in the endoplasmic reticulum; smaller fractions are found in the Golgi, at the cell surface, multivesicular endosomes, as well as in lysosomes. The stability of STS in lysosomes may be related to the high homology of the two luminal domains of STS with the lysosomal sulfatases, arylsulfatase A, and arylsulfatase B. In spite of its similarity with these two lysosomal sulfatases, STS does not contain mannose 6-phosphate residues and is transported to lysosomes by a mannose 6-phosphate receptor-independent mechanism.

Amino Acid Sequence↗
PubMed1989

Cloning and expression of human arylsulfatase A.

A full length cDNA for human arylsulfatase A was cloned and sequenced. The predicted amino acid sequence comprises 507 residues. A putative signal peptide of 18 residues is followed by the NH2-terminal sequence of placental arylsulfatase A. One of the arylsulfatase A peptides ends 3 residues ahead of the predicted COOH terminus. This indicates that proteolytic processing of arylsulfatase A is confined to the cleavage of the signal peptide. The predicted sequence contains three potential N-glycosylation sites, two of which are likely to be utilized. The sequence shows no homology to any of the known sequences of lysosomal enzymes but a 35% identity to human steroid sulfatase. Transfection of monkey and baby hamster kidney cells resulted in an up to 200-fold increase of the arylsulfatase A activity. The arylsulfatase A was located in lysosome-like structures and transported to dense lysosomes in a mannose 6-phosphate receptor-dependent manner. The arylsulfatase A cDNA hybridizes to 2.0- and 3.9-kilobase species in RNA from human fibroblasts and human liver. RNA species of similar size were detected in metachromatic leukodystrophy fibroblasts of two patients, in which synthesis of arylsulfatase A polypeptides was either detectable or absent.

Amino Acid Sequence↗
PubMed1989

Peripheral opioid receptors mediating antinociception in inflammation. Evidence for involvement of mu, delta and kappa receptors.

This study examined a possible peripheral site of action of opioids in the modulation of the response to noxious pressure on inflamed tissue. Rats developed a unilateral localized inflammation upon injection of Freund's complete adjuvant into one hindpaw. 4-6 days after inoculation, intraplantar administration of mu, delta and kappa selective agonists [D-Ala2,N-methyl-Phe4,Gly-ol5]-en-kephalin (1 micrograms), [D-Pen2,5]-enkephalin (40 micrograms) and U-50, 488H (50 micrograms) produced marked antinociceptive effects in inflamed but not noninflamed paws. Equivalent doses applied systemically (s.c. and i.v.) were without effect. Dose dependency and stereospecificity of these effects were demonstrated using (-)- and (+)-morphine and (-)- and (+)-tifluadom. Furthermore, by use of (-)- and (+)-naloxone, dose-dependent and stereospecific antagonism was shown. Lastly, reversal of effects of [D-Ala2,N-methyl-Phe4,Gly-Ol5]-enkephalin, [D-Pen2,5]-enkephalin and U-50,488H by mu, delta and kappa selective antagonists D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2, ICI 174,864 and nor-BNI, respectively, indicated that these agents interact with discriminable populations of receptors. These observations suggest that several selective opioid agonists can modulate responses to noxious pressure through a peripheral opioid receptor-specific site of action in inflammation and that these receptors possess distinguishable pharmacological characteristics resembling those of mu, delta and kappa receptors.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1988

Antinociceptive effects of mu- and kappa-agonists in inflammation are enhanced by a peripheral opioid receptor-specific mechanism.

Rats received an injection of Freund's complete adjuvant into the right hindpaw and developed localized inflammation. Four to six days after inoculation, the antinociceptive effect of both the mu-agonist, morphine, and the kappa-agonist U-50,488H, administered subcutaneously, was markedly enhanced in the inflamed paws. This effect was dose dependently antagonized by low dose of intraplantar, but not subcutaneous or intravenous, (-)-naloxone. (+)-Naloxone was inactive. These data indicate that the enhanced antinociceptive effects of both agonists in inflammation are mediated by a peripheral, opioid receptor-specific mechanism.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1988

Kinetic studies on nitrite and nitrate in rats by ion-pair chromatography.

A highly sensitive and specific ion-pair chromatographic method is presented for the simultaneous determination of nitrite (NO2-) and nitrate (NO3-) in plasma. The detection limits are 2 mumol NO2-/l and 8 mumol NO3-/l with recovery rates of 98-99%. The applicability of this method to clinical medicine is demonstrated using NO2- -loaded rats as a biological model: following intravenous infusion or intragastric application of NO2-, blood levels of NO2-, NO3- and methemoglobin are measured during 2-64 min. The kinetic data obtained reflect the complex metabolism of NO2- and NO3- in living organisms.

Animals↗
PubMed1988

Peripheral effect of fentanyl upon nociception in inflamed tissue of the rat.

This study examined a possible peripheral site of action of opiates in the modulation of the response to noxious pressure on inflamed paws. Rats received an injection of Mycobacterium butyricum suspension into one hindpaw which resulted in an ipsilateral inflammatory response (swelling) and decreased threshold to noxious pressure within 1-2 days. Four days post-inoculation direct intraplantar injection of fentanyl resulted in a significant increase of paw pressure thresholds in inflamed, but not in non-inflamed paws. Intraplantar injection of (-)-naloxone but not (+)-naloxone reversed this effect. The action of fentanyl was dose dependent at doses of 0.1-1.2 micrograms. Equal doses of fentanyl given systemically as well as (-)-naloxone or (+)-naloxone given alone were inactive. These data show that fentanyl can modify the response to noxious pressure in inflamed but not non-inflamed paws via a peripheral site of action. Stereospecific reversibility by naloxone as well as dose dependency strongly indicate an opioid mechanism of action. This suggests a possible role for peripherally located opioid receptors in the modulation of nociception in inflamed tissue.

Animals↗