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:3.4.16.2 (PCP)
3,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Opportunistic lung infections and malignancies are life-threatening complications in HIV-positive patients. In 72 HIV-positive patients the role of different non-invasive tests such as lung function tests, blood gas analysis, 67 gallium scanning and epithelial lung clearance with 99m Tc-DTPA for the management of these patients was prospectively studied. For all non-invasive tests the mean values of patients with pulmonary complications (n = 25) differed significantly from those of asymptomatic HIV-positive patients (n = 47) (p < 0.001). In 10 patients presenting with acute Pneumocystis carinii pneumonia, 99m Tc-DTPA clearance rates and 67 gallium uptake differed significantly before and after therapy (4.80 +/- 1.23%/min vs 2.47 +/- 0.72%/min and 2.15 +/- 0.42 vs 1.39 +/- 0.18, respectively). Follow-up after therapy revealed different time courses of these tests for normalization. A significant inverse correlation was found between DLCO and 99m Tc-DTPA lung clearance (r = -0.90, p < 0.001, n = 35). A diffuse homogeneous 67 gallium uptake is not diagnostic for PCP, the same pattern was found in a patient with lymphoid interstitial pneumonitis and in patients with CMV pneumonitis; these patients also had accelerated epithelial lung clearance rates. 67 gallium (6/6) was superior to 99m Tc-labelled immunoglobulin G (3/6) for detection of PCP. The 3 patients with Kaposi sarcoma of the lung had negative 67 gallium scans, but positive 201 thallium scans and increased 99m Tc-DTPA clearance rates.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Contribution of nuclear medicine to management of pulmonary complications in patients with acquired immune deficiency]. 838 18

The lungs are a primary target for the opportunistic infections and malignancies affecting those with HIV infection. In the patient whose HIV infection is undiagnosed, PCP is the commonest clue to its presence. Early diagnosis prevents morbidity and mortality. Less commonly, interstitial lung disease and tuberculosis, often "primary" or clinically atypical, will be the clue to underlying HIV infection. Other pulmonary complications are usually a late manifestation of HIV infection, which has usually (but not always) already been diagnosed.
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PMID:HIV-related respiratory disease. 841 49

We studied the characteristics and temporal trends of AIDS- associated non-Hodgkin's lymphoma (AIDS-NHL) in individuals with hemophilia. Prospective data were collected on 33 HIV-positive hemophiliacs with AIDS-NHL enrolled in the Hemophilia Malignancy Study (HMS), of whom 21 had primary and 12 had secondary or subsequent AIDS-defining illnesses, and analyzed for frequency and temporal trends. As compared with primary AIDS- NHL, secondary AIDS-NHL occurred at an older mean age, 37 versus 29 years (p = 0.12); at a lower mean CD4 count, 46 versus 154 (p = 0.07); after a longer period of immunosuppression (CD4 < 200/microl), 41 versus 16 months (p = 0.03); and with shorter median survival, 2 versus 7 months (p = 0.09). The presence of EBV in tumor tissue was associated with shorter survival, 1 versus 7 months (p = 0.17). Between 1981 and 1988 and 1989 and 1994, the proportion of primary AIDS diagnoses that were AIDS-NHL changed minimally, 4.6 versus 6.1%, whereas there were significant decreases in Pneumocystis carinii pneumonia (PCP, p = 0.02) and wasting (p = 0.07), and an increase in Candida (p = 0.004). These findings confirm that an increasing proportion of AIDS-NHL in hemophiliacs are occurring as secondary or later AIDS diagnoses, and they are associated with prolonged duration of immunosuppression.
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PMID:AIDS-associated non-Hodgkin's lymphomas as primary and secondary AIDS diagnoses in hemophiliacs. Hemophilia Malignancy Study Group. 879 89

The opportunistic infections, malignancies, and causes of death related to acquired immunodeficiency syndrome (AIDS) are changing, perhaps as a result of improved treatment, prophylaxis, and education. With its high percentage of persons who acquired the human immunodeficiency virus from intravenous drug (IVD) use, the population of patients with AIDS in the Bronx is potentially unique. All of the 257 consecutive adult human immunodeficiency virus and/or AIDS cases from two Bronx teaching hospitals from 1982 through 1995 were collected. The reports were reviewed for patient demographics, opportunistic infections, malignancies, and causes of death. One hundred thirteen cases from 1982 through 1988 were compared with 144 cases from 1989 through 1995, separated by the institution of antiretroviral therapy and Pneumocystis carinii (PCP) prophylaxis in the latter period. Male homosexuality as a risk factor significantly decreased from 24.8% of the cases in our study from the 1982/88 period to 12.5% during the 1989/95 period (P = 0.014), but IVD use cases showed no change. Cases of AIDS in heterosexual patients increased from 23.9 to 36.1% (P = 0.041) but did not achieve statistical significance unless the unknown risk category (a population shown to be infected predominantly through heterosexual transmission) was included. The prevalence of PCP at autopsy as an opportunistic infection decreased from 37.2 to 25% (P = 0.04), and its prevalence as a cause of death decreased from 31.9 to 13.9% (P = 0.007). This decrease was seen in the homosexual and heterosexual populations but not in the population of IVD users. The homosexual population, as opposed to the population of IVD users, may have taken greater advantage of PCP treatment and prevention. As a result, bronchopneumonia, not PCP, is now the leading cause of death among the patients with AIDS in this study. These findings have important implications for therapy and prophylaxis to control the spread of AIDS and its related infections, particularly in an inner city population troubled by drug use and poverty.
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PMID:Comparison of changing autopsy trends in the Bronx population with acquired immunodeficiency syndrome. 890 38

Procalcitonin (ProCT) is a recently described marker of severe sepsis. It was decided to assess the value of proCT as a marker of secondary infection in patients infected with HIV-1. ProCT plasma levels were measured by immunoluminometric assay in a prospective study in 155 HIV-infected individuals: 102 asymptomatic and 53 with lever or suspected secondary infections. The baseline plasma level of ProCT was low (0.5 ng/ml +/- 0.37), even in the latest stages of the disease, and did not differ from the values of healthy subjects (0.54 ng/ml +/- 0.08). EDTA-treated whole blood was collected from patients before starting specific antimicrobial therapy. No elevation of ProCT level was detected in HIV-infected patients with evolving secondary infections including PCP (n = 4), cerebral toxoplasmosis (n = 4), viral infections (n = 9), mycobacterial infections (n = 5), localized bacterial (n = 12) and fungal infections (n = 4), malignancies (n = 3), and in various associated infectious and non-infectious febrile events (n = 13). All these plasma values were lower than 2.1 ng/ml. In contrast, high ProCT plasma levels were detected in one HIV-infected patient with a septicaemic Haemophilus influenzae infection (16.5 ng/ml) and another one with a septicaemic Pseudomonas aeruginosa infection (44.1 ng/ ml), ProCT values decreased rapidly under appropriate therapy. ProCT seems to be a specific marker of bacterial sepsis in HIV-infected patients, as no increase in other secondary infections could be detected in those patients. A rapid determination of ProCT level could be useful to confirm or refute bacterial sepsis for a better management of febrile HIV-infected patients.
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PMID:Procalcitonin as a marker of bacterial sepsis in patients infected with HIV-1. 927 23

Adenocarcinomas of the nose are regarded as an occupational disease in Germany and other European countries, and workers exposed to oak or beech wood-dust in the course of their work receive compensation if they incur adenocarcinoma of the nose. This has prompted a joint research project to record the functional and morphological changes of the nasal mucosa and/or paranasal sinus of 149 exposed subjects and 33 controls in accordance with a defined occupational exposure. To ensure the quantitative and qualitative reliability of the exposure data, 1,349 measurements at the company workplace were taken and analyses of 614 wood samples performed; parallel to this, the genotoxic effects of the most important substances used in the wood-working industry were tested. Apart from this, latency periods and morbidity rates in Germany were investigated. Partial findings of this research projects have been evaluated by the International Agency for Research on Cancer (IARC). According to these evaluations and the findings presented here, the following points can be made: i) Morphological changes in the nasal mucosa after exposure to wood-dust resulted in an increase in cylindrocellular hyperplasias and, in functional terms, a tendency towards improved nasal clearance was observed. Chromium and formaldehyde, on the other hand, tended to give rise to an increase in the number of squamous metaplasias. This might explain the preference for the histological types of adenocarcinoma among subjects exposed to wood-dust. ii) In tissue samples more dysplasias were found among those exposed to oak and beech wood-dust. Subjects exposed to wood preserving agents had dysplasias only if they were simultaneously exposed to oak and beech wood-dust. The latter effect did not quite reach the level of significance (p = 0.07) on account of the low numbers of cases. iii) The investigation of genotoxic effects showed that oak and beech contain genotoxic substances that can be dissolved by means of ethanol and cyclohexane; they also showed that 3 out of 8 wood preservatives, 5 out of 16 stains, and 2 out of 11 paints from the wood-working industry are genotoxic too. Apart from this, lindane and PCP have proved to be genotoxic in the nasal cells of rats and human beings. Analysis of 614 wood samples from wood-preserving agents showed that almost 73% contained agents of this type, even in woods described by the companies as being guaranteed free of wood preservatives. iv) According to an analysis of 147 cases accepted since 1985 as a pensionable occupational illness by the Holz-Berufsgenossenschaft (an industrial compensation society for employees in the wood-working industry), the disease was much more apparent in small companies where there is multi-factorial exposure, than in large companies where the exposure factor tends to have a single component. This points to the combined effects of hardwood dusts and chemicals as being the cause. v) According to published findings, the incidence of the disease in England seems to be on the decline. In Germany, increasing latency periods also point to a decline in the number of cases, although both countries have only very recently introduced effective prevention measures against exposure to wood-dust. This also leads to the assumption that wood-dusts cannot be the only cause of this type of cancer. vi) These findings tally with the evaluation by the IARC confirming the special part that hardwood dusts play in the development of nasal cancer. The findings presented here also indicate combined effects as being the cause of this type of cancer. This hypothesis cannot be confirmed until the conclusion of long-term animal experiments, currently being conducted, to test how the effects of chemicals such as lindane, PCP, and chromate compare with use of oak wood-dust.
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PMID:The role of combination effects on the etiology of malignant nasal tumours in the wood-working industry. 972 90

Vascular endothelial growth factor (VEGF) is a dimeric protein which induces formation of new blood vessels (angiogenesis) through binding to VEGF-receptor-2 tyrosine kinase (VEGFR2 TK) or KDR (kinase insert domain-containing receptor) on the surface of endothelial cells. Angiogenesis has been shown to be essential for malignancy of tumors; therefore, VEGFR2 TK is a potential therapeutic target for the treatment of cancer. Sequence homology studies indicate that VEGFR2 TK contains three domains: extracellular (ligand-binding domain), transmembrane, and intracellular (catalytic domain). In this work, the catalytic domain of VEGFR2 TK was cloned and expressed in a soluble active form using a baculovirus expression system. In the absence of ligand, the enzyme is shown to catalyze its autophosphorylation in a time-dependent and enzyme-concentration-dependent manner, consistent with a trans mechanism for this reaction. Mass spectrometry analysis revealed incorporation of 5.5 +/- 0.5 mol of phosphate/mole of enzyme (monomer). In addition, the enzyme was shown to catalyze phosphorylation of a synthetic peptide, poly(E4Y). Using poly(E4Y) as substrate, the kinetic constants of both native and phosphorylated enzyme were determined. Enzyme phosphorylation increased catalytic efficiency of the enzyme by at least an order of magnitude. Furthermore, the enzyme was shown to catalyze the reverse reaction using phospho-poly(E4Y) as substrate. Cd2+ was found to be an inhibitor of the enzyme. Kinetic studies revealed that inhibition by Cd2+ was competitive with respect to Mg2+ and noncompetitive with respect to MgATP. These results indicate that Cd2+ competes for a second metal-binding site. Therefore, the reaction catalyzed by this enzyme was treated as a terreactant system. The kinetic mechanism of VEGFR2 TK was elucidated through the use of steady-state kinetic studies. According to these studies, the enzyme binds Mg2+ and MgATP in a random fashion followed by ordered addition of the peptide substrate. The release of product is also ordered, with MgADP being released last. The order of substrate binding was confirmed by using AMP-PCP, a dead-end inhibitor.
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PMID:Characterization and kinetic mechanism of catalytic domain of human vascular endothelial growth factor receptor-2 tyrosine kinase (VEGFR2 TK), a key enzyme in angiogenesis. 984 50

In the present study we have examined the effects of brominated flame retardants (BFR) and several other environmental contaminants in two in vitro assays for intragenic recombination at an endogenous locus in mammalian cells. A total ten compounds were investigated, i. e., two technical PCB mixtures (Aroclor 1221 and Aroclor 1254), DDT, PCP, tetrabromobisphenol A (TBBPA), 4,4'-bischlorophenyl sulfone (BCPS), hexabromocyclododecane (HBCD) and the three different polybrominated diphenylethers (PBDEs): 2-bromodiphenylether (MBDE), 3,4-dibromodiphenylether (DBDE) and 2,4,2', 4'-tetrabromodiphenylether (TBDE). In the SPD8 assay system statistically significant increases in recombination frequency were observed with Aroclor 1221, BCPS, DBDE, DDT, HBCD, MBDE and TBDE. In the Sp5 assay system, only DBDE, HBCD and MBDE caused statistically significant increases in recombination frequency. In conclusion, our findings indicate that the modern additives to plastic, i.e., HBCD and PBDEs, as well as the plastic monomer BCPS may have the same effect to human health as DDT and PCBs, in terms of inducing genetic recombination, which is known to provoke a number of diseases, including cancer.
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PMID:Brominated flame retardants induce intragenic recombination in mammalian cells. 1002 42

Coordinate regulation of fibrinolytic and collagenolytic systems is essential for normal tissue remodeling and wound healing. To define the molecular mechanisms which link these two proteolytic systems, we have investigated the role of fibrin in matrix metalloproteinase (MMP) function. Both active and latent forms of MMP-9 (gelatinase B) bind to fibrin in a selective, dose-dependent manner; latent enzyme is activated by plasmin during fibrinolysis. Fibrin binding of MMP-9 is mediated by amorphous calcium phosphate (ACP), and proceeds in a step-wise fashion with formation of ACP as the first and rate-limiting step. MMP-9 rapidly binds preformed ACP to yield a transient ACP: MMP-9 complex that avidly binds fibrin. Here we report the effect(s) on fibrin: ACP: MMP-9 formation/dissociation of pyrophosphate (POP), an endogenous calcification inhibitor, and its bisphosphonate analog, alendronate (PCP). MMP-9 was obtained from neutrophil lysate and ACP formation was monitored turbidimetrically. Free MMP-9, ACP: MMP-9 and fibrin: ACP: MMP-9 complexes were analyzed by gelatin zymography. POP at physiologic concentrations (0.5-2.5 microM) inhibited both ACP formation and subsequent fibrin binding of MMP-9 at orthophosphate concentrations of 250 microM. PCP exhibited a similar inhibitory effect. With both substances, inhibition was slightly overcome (>2.5 microM) by higher phosphate (500 microM). In contrast, supraphysiologic concentrations of either POP or PCP (>50 microM) were required to inhibit MMP-9 binding to preformed ACP or to induce dissociation of preformed ACP: MMP-9 complexes (50-100 microM). Neither POP nor PCP had any effect on preformed fibrin: ACP: MMP-9 at concentrations up 1 mM. POP is an endogenous by-product of numerous metabolic pathways and may regulate bone turnover, soft tissue calcification, and contribute to the pathogenesis of calcium pyrophosphate crystal disease (CPPD). These studies support another role for POP and fibrin: ACP: MMP-9 complexes in physiologic and pathologic processes, including tumorigenesis and cancer metastasis.
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PMID:Amorphous calcium phosphate-mediated binding of matrix metalloproteinase-9 to fibrin is inhibited by pyrophosphate and bisphosphonate. 1044 97

Pentachlorophenol has been used as an herbicide, algicide, defoliant, wood preservative, germicide, fungicide, and molluscicide. Pentachlorophenol was nominated by the National Cancer Institute for carcinogenicity testing based on its widespread use as a wood preservative, potential for entering the environment (pentachlorophenol residues have been found worldwide in soil, water, and air samples; in food products; and in human and animal tissues and body fluids), and likelihood of bioaccumulation in the environment (pentachlorophenol is persistent in soil, having a half-life of up to 5 years). Technical Report No. 349 contains the results of the 2-year studies of pentachlorophenol performed by the NTP with B6C3F1 mice. Male and female F344/N rats were exposed to pentachlorophenol (approximately 99% pure) in feed for 28 days or 2 years. Genetic toxicology studies were conducted in vitro in Salmonella typhimurium and cultured Chinese hamster ovary cells and in vivo in rat and mouse bone marrow cells. 28-DAY STUDY IN RATS: Groups of 10 male and 10 female F344/N rats were given 0, 200, 400, 800, 1,600, or 3,200 ppm pentachlorophenol, equivalent to average daily doses of approximately 20, 40, 75, 150, or 270 mg pentachlorophenol/kg body weight to males and females in feed for 28 days. With the exception of one male and two females exposed to 3,200 ppm, all rats survived until the end of the study. The final mean body weights and body weight gains of male rats exposed to 1,600 or 3,200 ppm and female rats exposed to 400, 800, 1,600, or 3,200 ppm were significantly less than those of the controls; rats exposed to 3,200 ppm lost weight during the study. Feed consumption by 3,200 ppm males was less than that by the control group throughout the study. The absolute and relative liver weights of 400, 800, and 1,600 ppm males and all exposed groups of females were significantly greater than those of the controls. Compared to the control groups, the incidences of minimal to mild hepatocyte degeneration in males and females exposed to 400 ppm or greater and the incidences of centrilobular hepatocyte hypertrophy in the 3,200 ppm groups were increased. 2-YEAR STUDY IN RATS: Groups of 50 male and 50 female rats were fed diets containing 200, 400, or 600 ppm pentachlorophenol (equivalent to average daily doses of approximately 10, 20, and 30 mg/kg) for 105 weeks. Stop-exposure groups of 60 male and 60 female rats received 1,000 ppm (equivalent to 60 mg/kg) in feed for 52 weeks, after which animals received undosed feed for the remainder of the 2-year study; 10 male and 10 female control and 1,000 ppm rats were evaluated at 7 months. Survival, Body Weights,and Feed Consumption: In the 2-year study, survival of 600 and 1,000 ppm males was greater than that of the controls. Mean body weights of 400 and 600 ppm males and females were generally less than those of controls. When exposure to pentachlorophenol was discontinued at week 52, mean body weights of 1,000 ppm males and females were 17%% and 22%% lower than those of the respective controls; however, by the end of week 87, the mean body weights were similar to those of the controls. Generally, feed consumption by exposed groups was similar to that by the controls. Pathology Findings: At 2 years, the incidence of malignant mesothelioma originating from the tunica vaginalis was significantly greater in 1,000 ppm males than in the controls, and the incidence exceeded the historical control range. Nasal squamous cell carcinomas were present in one control male, three 200 ppm males, one 400 ppm male, and five 1,000 ppm males at 2 years, and the incidence in 1,000 ppm males exceeded the historical control range. At the 7-month interim evaluation, the incidences of centrilobular hepatocyte hypertrophy in 1,000 ppm males and females and hepatocyte cytoplasmic vacuolization in 1,000 ppm males was significantly greater than those in the controls. At 2 years, the incidences of several nonneoplastic liver lesions including hepatodiaphragmatic nodules and hepatocyte cystic degeneration in all exposed ation in all exposed groups of males and basophilic foci in 1,000 ppm males were increased compared to the controls. GENETIC TOXICOLOGY: Pentachlorophenol (91.6%&percnt; pure) was tested in Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537 at doses up to 30 &mu;g/plate with and without induced rat or hamster liver S9; no significant increases in the number of revertant colonies were observed in any of the strain/activation combinations. When tested for cytogenetic effects in cultured Chinese hamster ovary cells, pentachlorophenol was weakly positive for induction of sister chromatid exchanges and chromosomal aberrations. In the sister chromatid exchange test, a weakly positive response was observed within a concentration range of 3 to 30 &mu;g/mL in the absence of S9; with S9, no induction of sister chromatid exchanges was noted. In the chromosomal aberrations test, pentachlorophenol was negative without S9 but induced small but significant increases in the frequency of aberrant cells in the presence of S9 at doses of 80 and 100 &mu;g/mL. In contrast to the positive in vitro results in the test for induction of chromosomal aberrations, no increase in the frequency of micronucleated erythrocytes was noted in bone marrow of male rats or mice administered pentachlorophenol by intraperitoneal injection three times at 24 hour intervals. The highest dose administered to rats (75 mg/kg) and mice (150 mg/kg) was lethal. CONCLUSIONS: Under the conditions of this 2-year feed study, there was no evidence of carcinogenic activity of pentachlorophenol in male or female F344/N rats fed diets containing 200, 400, or 600 ppm. There was some evidence of carcinogenic activity of pentachlorophenol in male F344/N rats given feed containing 1,000 ppm for 1 year followed by control feed for 1 year (stop-exposure study), based on increased incidences of mesothelioma and nasal squamous cell carcinoma. There was no evidence of carcinogenic activity of pentachlorophenol in female rats given feed containing 1,000 ppm for 1 year and maintained on control feed for 1 year. Stop-exposure males and females recovered from a transitory reduction in body weight gain by the end of the 2-year study, and males had increased survival compared to the controls. Synonyms: Chlorophen; PCP; penchlorol; penta; pentachlorofenol; pentachlorofenolo; 2,3,4,5,6-pentachlorophenol Trade names: Acutox; Chem-Penta; Chem-Tol; Cryptogil ol; Dowicide 7; Dowicide EC-7; Dow Pentachlorophenol DP-2 Antimicrobial; Durotox; EP 30; Fungifen; Fungol; Glazd Penta; Grundier Arbezol Lauxtol; Lauxtol A; Liroprem; Moosuran; Pentacon; Penta-Kil; Pentasol; Penwar; Peratox; Permacide; Permagard; Permasan; Permatox; Priltox; Permite; Santophen; Santophen 20; Sinituho; Term-i-Trol; Thompson's Wood Fix; Weedone; Witophen P
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PMID:NTP Toxicology and Carcinogenesis Studies of Pentachlorophenol (CAS NO. 87-86-5) in F344/N Rats (Feed Studies). 1257 80


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