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At least 19 recordsLinked to original sources
PubMed1998

Inhibition, reactivation and aging kinetics of cyclohexylmethylphosphonofluoridate-inhibited human cholinesterases.

Cyclohexylmethylphosphonofluoridate (cyclosarin) is a highly toxic organophosphate, which was shown to be rather resistant to conventional oxime therapy. To give more insight into the inhibition, reactivation and aging kinetics, human acetyl-(AChE) and butyrylcholinesterase (BChE) were inhibited by cyclosarin (k2 of 7.4 and 3.8 x 10(8) M(-1) min(-1), respectively; pH 7.4, 37 degrees C) and reactivated with obidoxime, pralidoxime and three experimental oximes. The new oxime HLö 7 (1-[[[4-aminocarbonyl)-pyridinio]-methoxy]-methyl]-2,4-bis-[ (hydroxyimino)methyl] pyridinium dimethanesulphonate) was shown to be superior to the other oximes. At oxime concentrations anticipated to be relevant in humans, obidoxime and pralidoxime were extremely weak reactivators of AChE. Aging velocity of BChE was almost fourfold higher compared to AChE (ka of 0.32 h(-1) and 0.08 h(-1), respectively). A substantial spontaneous reactivation was observed with AChE. These results support previous in vivo findings that obidoxime and pralidoxime are insufficient antidotes in cyclosarin poisoning. By contrast, HLö 7 was shown to be an extremely potent reactivator of human AChE and BChE, which supports its position as a broad-spectrum oxime.

Acetylcholinesterase↗
PubMed1979

Effector localization and transfer of reactive inhibition.

An experimental test was made of Hull's (1943) notions that reactive inhibition is effector-specific and that it has primary negative motivational properties. Four groups of 20 subjects (10 males and 10 females in each) executed two segments of continuous right-hand practice on a mirror-tracking task. The two segments were separated either by 0 min rest, 5 min rest, 5 min continuous right-hand practice on rotary pursuit, or 5 min continuous left-hand practice on rotary pursuit. Effects of interpolated conditions were measured in terms of main-task reminiscence arid initial post-treatment performance. When interpolated practice was conducted with the right hand, reminiscence and post-treatment performance were significantly depressed relative to the rest effect, but not when interpolated practice was conducted with the left hand. Thus, Hull's views were supported, while competing views, such as the task specificity concept of lr and the consolidation theory of reminiscence, were impugned.

Journal Article↗
PubMed1990

Inhibition reactivation myofibrillar ATPase technique for demonstration of three fiber types in a single cryostat muscle section.

An inhibition reactivation technique was used for histochemical staining of human skeletal muscle sections. Myofibrillar ATPase activity was inhibited by sodium hydroxymercuribenzoate (2.5 mM in 0.1 M Tris-HCl buffer, pH 7.2-7.5, 30 min) and successively reactivated by cysteine which was added to incubation solution (10 mM cysteine-HCl, 2.5 mM ATP-disodium salt, 50 mM potassium chloride and 27 mM calcium chloride in barbital buffer, pH 9.4, 35 min at 37 C). This technique allows the distinction of three fiber categories with different staining intensities in single cross-section. Dark, intermediate and light fibers correspond to IIB, I, and IIA types, respectively. Storage of air dried sections in the freezer at -20 C for one month had no influence on staining characteristics.

Adenosine Triphosphatases↗
PubMed1980

High incidence of migration inhibition reactivity to lung tumor-associated antigen by normal donors in close contact with lung cancer patients or materials.

A high incidence of indirect leukocyte migration inhibition reactivity of normal donors to a 3-M KCl extract from a fresh pleural effusion of a patient with a lung adenocarcinoma (designated 7661) was observed. When these normal donors were classified according to contact with lung cancer patients or materials, 22 of 32 (72%) normal donors in contact with lung cancer patients or materials were reactive with the 7661 extract as compared to only 3 of 76 (4%) who had no contact. Of normal donors involved in the direct care of lung cancer patients, 14 of 20 (70%) were positive, whereas only 2 of 10 (20%) hospital personnel who worked with noncancer patients were reactive. Among laboratory personnel who handled blood and tissue specimens from lung cancer patients, 8 of 11 (73%) were positive with the 7661 extract, whereas none of 5 laboratory workers who worked with cancer materials unrelated to lung cancer were positive. Also, none of 13 personnel working in laboratories adjacent to those where lung cancer tests were performed were reactive with 7661. None of the 16 blood bank donors and none of 11 secretarial and clerical staff who worked in biochemical laboratories were positive. Reactivity was no correlated with a smoking history. Thus development of reactivity appeared to require direct contact with lung cancer patients or materials. The results suggested a horizontal transmission of reactivity against an antigen associated with lung cancer.

Adenocarcinoma↗
PubMed1992

Fiber differentiation of the human laryngeal muscles using the inhibition reactivation myofibrillar ATPase technique.

The aim of the present study was to further subdivide the type II fibers of the human thyroarytenoid and posterior cricoarytenoid muscles by means of a modified myosin ATPase reaction. In order to understand the functioning of these highly strained muscles better, it is important to know the respective percentage of fatigue-resistant type IIA fibers and fatigable type IIB fibers. The material comprised the larynges of seven laryngectomized males aged between 45 and 70 years and four laryngectomized females aged between 39 and 72 years. After having been frozen in nitrogen, 10-microns-thick sections were cut from the laryngeal muscles in a cryostat. The pH-lability of the enzyme that can be utilized in a classical myosin ATPase reaction permits a differentiation between fiber types I, IIA and IIB. Evidently, this is not possible with every human muscle. The fiber types IIA and IIB of the thyroarytenoid and the posterior cricoarytenoid muscles could be clearly distinguished by means of the inhibition reactivation myofibrillar ATPase technique. Using this method, the myosin ATPase enzyme was initially inhibited by hydroxymercuribenzoate and subsequently reactivated by cysteine. Regarding the incidence of type I and IIA fibers, there was a statistically significant difference between the thyroarytenoid and the posterior cricoarytenoid muscles. The type IIA fiber content was statistically significantly higher in the arytenoid muscle than in the posterior cricoarytenoid muscle. The percentage of type IIB fibers was low, not only in the thyroarytenoid muscle and the posterior cricoarytenoid muscle but also in the other laryngeal muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphatases↗
PubMed1999

Dimethylphosphoryl-inhibited human cholinesterases: inhibition, reactivation, and aging kinetics.

Human poisoning by organophosphates bearing two methoxy groups, e.g. by malathion, paraoxon-methyl, dimethoate and oxydemeton-methyl, is generally considered to be rather resistant to oxime therapy. Since the oxime effectiveness is influenced not only by its reactivating potential but also by inhibition, aging and spontaneous reactivation kinetics, experiments were performed with human acetyl- (AChE) and butyrylcholinesterase (BChE) to determine the respective kinetic constants. The efficacy of obidoxime in reactivating dimethylphosphoryl-AChE was 40, 9 and 3 times higher than of HI 6, pralidoxime and HLö 7, respectively. Aging (t1/2 3.7 h) and spontaneous reactivation (t1/2 0.7 h) occurred concomitantly, with the portion of the aged enzyme being dependent on the presence of excess inhibitor. Calculation of steady-state AChE activity in the presence of inhibitor and oxime revealed that obidoxime was superior to pralidoxime. In addition, organophosphate concentrations up to 10(-6) M (paraoxon-methyl) and 10(-4) M (oxydemeton-methyl) could be counteracted at clinically relevant oxime concentrations (10 microM). These data indicate that oximes may effectively reactivate human dimethylphosphoryl-AChE. Failure of oximes may be attributed to megadose intoxications and to prolonged time intervals between poison uptake and oxime administration. The potency of the oximes to reactivate dimethylphosphoryl-BChE was much lower and the spontaneous reactivation slower (t1/2 9 h), while aging proceeded at a comparable rate. Thus, BChE activity determination for diagnosis and therapeutic monitoring may give no reliable information on AChE status.

Acetylcholinesterase↗
PubMed1993

Cocaine reduces macrophage killing by inhibiting reactive nitrogen intermediates.

The present study describes the inhibition of macrophage-mediated cytotoxicity (MMC) by cocaine and suggests a possible mechanism. Mice (C57BL/6) were injected i.p. with cocaine. At various intervals after exposure to cocaine, peritoneal macrophages (M phi) were removed, cultured in the presence of interferon gamma and LPS, then incubated with 51Cr labeled target cells. A single injection of > or = 10 mg/kg cocaine was sufficient to inhibit cytotoxicity to P815 cells. This inhibition was evident 3 h after exposure to cocaine and could still be demonstrated 24 h later. Since reactive nitrogen intermediates (RNI) have been reported to be one of the major mechanisms by which M phi kill, the amounts of NO2- produced by M phi from cocaine-injected animals were compared with that produced by equivalent controls. Cocaine reduced the level of NO2- in a dose-dependent manner which correlated with MMC. There was a significant reduction in NO2- produced by activated M phi, 3 h after i.p. injection of cocaine but not at 24 h, using > or = 5 mg/kg. At 12 h there were differences between M phi from control animals and animals receiving > or = 10 mg/kg cocaine. By 24 h there were no differences between control and cocaine-injected animals even at the highest dose employed (25 mg/kg). These results suggest that cocaine reduces the killing ability of murine M phi through a temporary reduction of RNI.

Animals↗