Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.3.1.21 (CPT)
4,580 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of the investigation was to throw light on the question whether drugs other than antibiotics and chemotherapeutic agents exert an antimicrobial effect. In order to elucidate this, the antimicrobial effect of selected psychotherapeutic drugs and their stereo-isomeric analogues was studied. The development of psychotherapeutic drugs from aniline dyes has been reviewed against the background of its history considered as a scientific idea. It is demonstrated that psychotherapeutic drugs have an antimicrobial effect. Psychotherapeutic drugs show antimicrobial activity at high concentrations. Stereo-isomeric analogues of known psychotherapeutic drugs also have an antimicrobial effect. The selectivity of the various stereo-isomeric compounds depends on which microorganism and which chemical compound is investigated. Synergism is found between psychotherapeutic drugs (CPZ) and penicillin in vitro, and between a non-neuroleptic stereo-isomeric compound trans-CPT and penicillin in vivo, using infected mice as material. The antibacterial activity of psychotherapeutic drugs is independent of the antihistaminic, antihypersecretory, neuroleptic and antidepressant effect of these drugs. The examples chosen of investigations of the antimicrobial effect of psychotherapeutic drugs in vitro and in vivo lead to the conclusion and to the perspectives in the present study. Namely, the need for a general theory of the interplay between host organism, microorganisms and drugs. This proposition is based on a concern to argue against the view that the prokaryotic effect of eukaryote-directed drugs is without major significance, either for scientific research or for clinical treatment.
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PMID:The antimicrobial activity of psychotherapeutic drugs and stereo-isomeric analogues. 218 4

As health care costs continue to rise, alternatives to the traditional fee for service system of physician reimbursement are being explored. Recently a resource-based relative-value system was enacted by Congress to correct some of the perceived inequities of Medicare reimbursement. Since reimbursement for evaluation and management services, also known as cognitive services, are based on Current Procedural Terminology (CPT-4) codes, we reviewed Medicare claims data for fiscal year 1986-87 to identify the coding habits of Connecticut urologists. We found that Connecticut urologist file 99% of their claims for cognitive services in one of six categories. Furthermore, we found that within these broad categories an average of 82% of the claims were filed under one primary practice specific code. The particular code selected, however, varied markedly between practices. Our data suggest that Connecticut urologists have adopted different standards for using CPT-4 codes and have adjusted for these differences through their fee schedules. These findings highlight the need for increased precision in CPT code definitions for cognitive services before they can be adapted to a reimbursement system based upon relative-value scales.
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PMID:Variations in coding practices among Connecticut urologists for the Medicare population. 222 18

1. Confirming previous work [Murthy & Pande (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 378-382], malonyl-CoA-inhibitable carnitine palmitoyltransferase (CPT1) from rat liver was found to be localized in outer rather than in inner mitochondrial membranes. 2. Antisera were raised against a liver mitochondrial CPT of Mr 68,000, which was presumed to be the latent from of the enzyme (CPT2). These antisera cross-reacted with solubilized CPT extracted from liver inner mitochondrial membranes and with polypeptides of Mr 68,000 and 60,000 in immunoblots of both inner and outer mitochondrial membranes. The antisera also precipitated CPT activity from detergent-treated total membrane and outer-membrane preparations. 3. The antisera did not precipitate [14C]malonyl-CoA binding material obtained either from total membranes or from outer membranes. 4. It was concluded that liver CPT1 and CPT2 have some epitopes in common and may have a similar subunit size. In addition, CPT1 and the entity that binds malonyl-CoA must be separated polypeptides.
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PMID:The relationship of rat liver overt carnitine palmitoyltransferase to the mitochondrial malonyl-CoA binding entity and to the latent palmitoyltransferase. 224 11

A stout man was admitted to the hospital with acute rhabdomyolysis associated with macro creatine kinase (macro-CK, EC 2.7.3.2). This anomaly of CK was detected by gel electrophoresis as an atypical band between CK-MB and CK-MM, classified according to Stein's criteria (Clin Chem 1982; 28:19-24) as type 1, and identified by immunofixation electrophoresis as containing CK isoenzymes MM and MB and immunoglobulin A. Muscle biopsy showed that the etiology of rhabdomyolysis in this case was deficiency of carnitine palmitoyltransferase (CPT, EC 2.3.1.21) in the muscle. We report the first observation of macro-CK in a case of CPT deficiency; its presence may result from recurrent rhabdomyolytic attacks owing to CPT deficiency, and may suggest underlying enzymic abnormality in muscle.
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PMID:Macro creatine kinase in a case of carnitine palmitoyltransferase deficiency. 224 93

Recurrent heritable childhood myoglobinuria is a potentially fatal entity (mortality up to 35%) in which prompt diagnosis and treatment are critical. Sixty childhood cases have been reported between 1910 to 1988, most with undiagnosed etiologies. We have studied an additional 40 cases referred to CPMC (1980-1988), suggesting that this condition is largely underdiagnosed or unreported. We have found important differences between the childhood and adult-onset cases. Of 77 cases of adult-onset recurrent myoglobinuria, 45% have been diagnosed biochemically. In contrast, only 30% of the 60 childhood cases from the literature have been diagnosed; 11 with CPT deficiency and 7 with various glycolytic defects, and only 5 of our 40 childhood cases have been diagnosed, all with CPT deficiency. The 100 combined childhood cases can be divided into an exertional group (type I) with exertion as the leading precipitating factor (46 literature and 10 CPMC cases), a toxic group (type II) with infection and/or fever as the primary precipitant (14 literature and 23 CPMC cases), and 7 undefined cases. The type I group resembles the adult-onset group in which exercise is also the leading precipitating factor. There is a slight female predominance (male/female = 1:1.3) in the toxic group vs. a marked male predominance in the exertional and adult groups (4:1). Only 4 of 37 cases (11%) of the toxic group are diagnosed (all with CPT deficiency) vs. 19 of 56 cases (34%) of the exertional group (12 CPT, 7 glycolytic) and 45% of the adult group. The toxic group is also differentiated by a higher mortality rate and by the presence of additional clinical features, including ictal bulbar signs (8 of 18), encephalopathy (4 of 19), and seizures (2 of 7), as well as persistent cardiac abnormalities, developmental delay (4 of 17), and dysmorphic features (2 of 9). These clinical characteristics clearly differentiate the childhood from the adult cases and suggest the presence of more generalized disease processes and different biochemical etiologies. A study of the heritable causes of myoglobinuria is important because identification of the biochemical defect may elucidate the pathogenetic mechanism of the myoglobinuria and facilitate the development of rational treatment strategies aimed at circumventing or correcting the metabolic block.
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PMID:Recurrent childhood myoglobinuria. 226 36

The possible involvement of protein kinase C and/or a lipoxygenase product in the mechanism by which adenosine inhibits release of [3H]acetylcholine evoked by electrical pulses from [3H]choline-labelled hippocampal slices was examined. For comparison, the muscarinic autoreceptors were examined using carbachol. The order of potency of adenosine analogues (CHA = R-PIA greater than NECA much greater than CGS 21680, CV 1808) indicates that the adenosine receptor responsible is of the A1 subtype. Adenosine (10 microM) and R-PIA (0.1 microM) were virtually equiactive as inhibitors and were antagonized to an equal extent by 8-CPT with a potency (IC50 approximately 25 nM) which is also compatible with A1-receptor mediation. The effects of carbachol and of R-PIA were not antagonized by the lipoxygenase inhibitor NDGA (10 or 50 microM). Stimulation of protein kinase C by the phorbol ester 4 beta-phorbol 12,13-dibutyrate caused a concentration-dependent increase in stimulation-evoked 3H overflow, but did not antagonize the presynaptic inhibitory effect of R-PIA or carbachol (0.01-1 microM). Staurosporine (0.1 microM), which inhibited the stimulating effect of phorbol dibutyrate, did not alter the effects of carbachol or R-PIA. The presynaptic effects of phorbol dibutyrate, R-PIA and adenosine were reduced by pretreatment with N-ethylmaleimide (100 microM for 10 min), which inactivates G-proteins. The evoked transmitter release was unaffected by nifedipine (1 microM) in the presence and in the absence of phorbol dibutyrate. These results indicate that adenosine, by acting at presynaptic A1-receptors, reduces transmitter release by a mechanism that involves neither an NDGA-sensitive lipoxygenase nor protein kinase C. The results also indicate that the enhancement of transmitter release by phorbol esters is due to protein kinase C activation and that a G-protein may be involved in the effect but a dihydropyridine-sensitive L-type Ca2+ channel probably is not.
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PMID:Adenosine A1-receptor-mediated inhibition of evoked acetylcholine release in the rat hippocampus does not depend on protein kinase C. 226 53

Signal detection indices (perceptual sensitivity) were calculated to compare performance of 24 male schizophrenic inpatients and 24 controls (12 alcoholics and 12 normals) on 4 different CPT-tests. A standard version (St) employed 1 target (P = 0.166) and 5 nontargets. In condition V stimuli were presented visually, in condition A acoustically and in condition VA bimodally (1 target (P = 0.333) and 1 nontarget). Compared to controls schizophrenics exhibited lower levels of perceptual sensitivity in all 4 conditions. They were especially impaired when stimuli were presented either acoustically or when they had to monitor 2 modalities simultaneously. Perceptual sensitivity of schizophrenics was significantly lower in conditions V, A, and VA than in condition St. For controls only condition VA led to lower values. Because St was always presented first, the possible explanation that vigilance decrement over time is responsible for the lowered perceptual sensitivity had to be ruled out. It could be shown that schizophrenics did not differ in sensitivity between conditions being later in task sequence. Controls, however, showed a slight decrement over time. Thus our finding should to a large extent be attributed to different task requirements. Response criterion beta yielded inconsistent results.
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PMID:Signal detection indices in schizophrenics on a visual, auditory, and bimodal Continuous Performance Test. 228 35

In order to assess the potential usefulness of CPT as a diagnostic tool for ocular allergy, the correlation between skin/RAST tests and CPT was determined in 144 patients affected by allergic 'hay fever' type conjunctivitis. The results showed that an agreement between skin/RAST tests and CPT occurred in 71% of the cases (130/183). Of the 29% uncorrelated cases, 23% (43/183) were positive for at least one specific antigen by skin/RAST tests but not by CPT, while 6% (10/183) were positive for at least one specific antigen by CPT, but not by skin/RAST tests. CPT dramatically increased the histamine levels in tears (p less than 0.001). These findings show that (1) systemic tests can be misleading in that they may suggest a specific sensitisation which, in fact, does not involve the conjunctiva (systemic test positive/CPT negative); (2) CPT can identify local conjunctival sensitisation in the absence of a systemic sensitisation (systemic test negative/CPT positive); (3) CPT can demonstrate that allergic 'hay fever' type conjunctivitis may be related to allergens different from those responsible for a systemic sensitisation.
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PMID:Correlation between conjunctival provocation test (CPT) and systemic allergometric tests in allergic conjunctivitis. 228 52

A new water-soluble derivative of camptothecin, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11), did not exhibit potent antitumor activity in vitro against experimental tumor cells. The 50% effective doses of CPT-11 against KB and L1210 cells were 1100 and 5500 ng/ml, respectively. These values were markedly higher than those of camptothecin (CPT, 0.98 and 3.7 ng/ml) or 7-ethyl-10-hydroxycamptothecin (SN-38, 0.37 and 3.6 ng/ml). CPT-11 was found to be converted into SN-38 in mouse serum. In vitro incubation of CPT-11 in mouse serum or tissue homogenate enhanced the growth-inhibitory activity much more than that expected from the concentration of CPT-11. This enhancement of the activity coincided with that expected from the SN-38 concentration in incubated serum or homogenate, though the contribution of CPT-11 could not be refuted. SN-38 is considered to play a major role in the antitumor activity when CPT-11 is incubated in serum or homogenate. The plasma CPT-11 concentration decreased biexponentially after i.v. administration of CPT-11 into mice with a biological half-life of 0.8 to 1.1 h. The area under the plasma CPT-11 concentration-time curve showed dose dependency. The SN-38 concentration decreased for the first 30 min after administration and was then maintained for a few hours at about 0.1 microgram/ml after i.v. administration of 20 and 40 mg/kg of CPT-11 followed by the log-linear terminal phase with a half-life of about 2 h which was independent of the dose. It is suggested that the maintenance of plasma SN-38 concentration might be necessary for it to exhibit antitumor activity in vivo.
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PMID:Metabolism and pharmacokinetics of the camptothecin analogue CPT-11 in the mouse. 230 25

The goal of this study was to establish conditions for solubilization and characterization of CPTo, the malonyl-CoA sensitive form of mitochondrial carnitine palmitoyltransferase. CPTo of heart mitochondria is soluble in 1% octyl glucoside with retention of malonyl-CoA sensitivity. The degree of malonyl-CoA sensitivity is dependent on both the concentration of octyl glucoside and the presence of salt (KCl). In mannitol-sucrose, 0.5-1% octyl glucoside solubilizes CPTo without loss of malonyl-CoA sensitivity; however, either increasing the detergent concentration or addition of KCl promotes loss of malonyl-CoA sensitivity. The immunoglobulin fraction from immune serum obtained from rabbits immunized with the malonyl-CoA-insensitive form of CPT (CPTi) purified from beef heart mitochondria was used for preparation of an affinity column. The antibody column retained both malonyl-CoA-sensitive and -insensitive CPT activity without apparent selectivity. In addition to CPT, several other major protein bands were detected when the antibody column eluates were subjected to SDS-PAGE; however, native gel electrophoresis gives a large, high molecular weight, diffuse band. After elution of the antibody-CPT column with salt, a 68,000-Da protein is retained by the column. The retained protein contains the CPT activity, but it is not inhibited by malonyl-CoA. Thus, salt elution separates catalysis from inhibition. When the salt eluate is subjected to affinity chromatography using agarose-CoA, two protein peaks are obtained; both bind malonyl-CoA. One of the two fractions contains beta-hydroxyacyl-CoA dehydrogenase, beta-ketothiolase, and crotonase activity. These data show that octyl glucoside solubilized CPTo and CPTi are associated with a complex that contains beta-oxidation enzymes.
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PMID:Isolation of a malonyl-CoA-sensitive CPT/beta-oxidation enzyme complex from heart mitochondria. 235 May 40


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