Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.16.2 (PCP)
3,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The AIDS epidemic continues to spread in Georgia. Almost every medical specialty is affected in some manner by the increased number of patients being diagnosed and treated with AIDS or the AIDS-related complex. Radiology has a pivotal role in documenting various opportunistic complications so that further testing and therapy may be instituted. Because of the large number of AIDS patients that develop thoracic disease, we have reviewed many of the potential pulmonary complications and their radiographic findings. Certain patterns of disease may suggest etiologies, though admittedly the chest radiograph is nonspecific. Diagnosis must be confirmed with sputum culture, bronchial lavage, and biopsy or open lung biopsy. There are key features that should be kept in mind. P. carinii, the most common pathogen, and several other opportunistic agents usually present with a fine bilateral interstitial or ground glass appearance. The presence of mediastinal adenopathy and/or pleural effusion suggests an etiology other than PCP. These findings are indicative of mycobacterial infection, KS, or lymphoma. PCP can present as a focal pulmonary consolidation, but this is unusual, and bacterial pneumonia must be considered. Finally, a small percentage of persons will present with a normal chest x-ray despite the presence of pulmonary infection or neoplasm. In those cases gallium lung scanning can help identify the affected individuals.
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PMID:Pulmonary complications in AIDS: the radiographic manifestations. 271 44

The effects of technical grade pentachlorophenol (T-PCP) exposure on several immunological parameters were examined in adult C57Bl/6 mice following eight weeks of dietary exposure. Immune function tests included mitogen-induced lymphocyte blastogenesis, mixed lymphocyte reactivity (proliferation and cytotoxicity), spontaneous and boosted levels of natural killer (NK) cytotoxicity, and phagocytic activity of resident, thioglycollate-induced, and P815-tumor activated peritoneal macrophages. Thymic and splenic weights, spleen cellularity, percentages of splenic T and B cells, and bone marrow cellularity were also determined. The only statistically significant functional alteration observed in T-PCP exposed mice in these studies was a reduction in the lymphoproliferative response in mixed lymphocyte culture which occurred in the absence of any apparent effect on the generation of cytotoxic cells. Mitogen responses, NK cytotoxicity and macrophage phagocytosis were unaltered by exposure to T-PCP. No changes were observed in spleen or thymus weights or in spleen or bone marrow cellularity. A dose-responsive trend toward reduced T cell and increased B cell percentages in the spleen of T-PCP exposed mice was noted. The apparent functional resistance of T cells, macrophages, and NK cells to T-PCP is in contrast to the marked sensitivity of the humoral immune response to T-PCP induced suppression. The results are discussed in relation to the dioxin contaminants present in T-PCP.
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PMID:Effects of dietary technical pentachlorophenol exposure on T cell, macrophage and natural killer cell activity in C57Bl/6 mice. 315 92

Because AIDS patients frequently present with minimal symptomatology, radionuclide imaging with its ability to survey the entire body, is especially valuable. Gallium-67 citrate, the most commonly performed radionuclide study for localizing infection in these patients, is most useful for detecting opportunistic infections, especially in the thorax. A negative gallium scan, particularly when the chest X-ray is unremarkable, rules strongly against pulmonary disease. A negative gallium scan in a patient with an abnormal chest X-ray and Kaposi's sarcoma, suggests that the patient's respiratory distress is related to the neoplasm. Diffuse pulmonary parenchymal uptake of gallium in the HIV (+) patient is most often associated with PCP. While there are other causes of diffuse pulmonary uptake, the more intense or heterogeneous the uptake, the more likely the patient is to have PCP. Focal pulmonary uptake is usually associated with bacterial pneumonia although PCP may occasionally present in this fashion. Lymph node uptake of gallium is usually associated with Mycobacterium avium complex, tuberculosis, or lymphoma. When corresponding abnormalities are present on thallium scintigraphy lymphoma is likely. Gallium positive, thallium negative, studies suggest mycobacterial disease. Labeled leukocyte imaging is not useful for detecting opportunistic infections probably because of the inflammatory response incited by these organisms. Leukocyte imaging is, however, more sensitive for detecting bacterial pneumonia. In the abdomen, gallium imaging is most useful for identifying lymphadenopathy, while labeled leukocyte imaging is superior for detecting AIDS-associated colitides. In summary, radionuclide studies are valuable diagnostic modalities in AIDS. Their success can be maximized by tailoring the study to the individual's needs.
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PMID:The role of gallium and labeled leukocyte scintigraphy in the AIDS patient. 755 45

Phencyclidine hydrochloride (PCP) was tested for its ability to alter a variety of immune effector and regulatory functions in vitro. B6C3F1 murine splenic lymphocytes or elicited peritoneal macrophages were cultured in vitro with medium only or medium containing 10(-10)-10(-4) M PCP. Macrophages cultured with or without PCP were stimulated with lipopolysaccharide, and production of interleukin 6 (IL-6) and tumor necrosis factor (TNF) was assessed by bioassay. Cytotoxic T-cell effector function was determined following 5-day lymphocyte co-culture with tumor stimulator cells in the presence of PCP. In addition, the ability of T-lymphocytes to produce specific immunoregulatory cytokines IL-2 and IL-4 in the presence of PCP was quantitated by bioassay. B-lymphocyte function was determined by quantitating lymphocyte proliferation following stimulation with anti-IgM antibody and murine IL-4. Natural immunity was assessed by culturing lymphocytes with or without PCP for 24 h, then quantitating basal and IL-2 augmented natural killer (NK) cell activity. In the absence of effects on cell viability, significant suppression of IL-2 production by T-cells was noted at pharmacologically relevant PCP concentrations (1 microM). In vitro concentrations of 10 microM suppressed the generation of specifically sensitized cytotoxic T-cells. In addition, PCP significantly suppressed both IL-2-augmented NK function as well as B-lymphocyte proliferation. By comparison, macrophage IL-6 production was not affected by any concentration of PCP examined in this study.
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PMID:Phencyclidine exposure alters in vitro cellular immune response parameters associated with host defense. 823 30

111In leukocyte scintigraphy has high sensitivity and specificity for detecting abdominal and pelvic infections. For abdominal imaging, 111In leukocyte imaging is preferred to 67Ga citrate imaging. If localizing signs are present, CT is the preferred imaging technique. In the lungs, gallium imaging is preferred to leukocyte imaging for identifying active inflammatory processes. Gallium imaging provides quantitative information about inflammatory activity that is not apparent from chest CT scans. Although both gallium and leukocyte imaging have a role in patients with fever of unknown origin, gallium imaging may be preferred because it can be used to detect occult tumor as well as more chronic infectious foci. In patients who have AIDS, gallium imaging is particularly reliable in detecting and monitoring response to therapy of PCP. In febrile AIDS patients without localizing signs, 111In leukocyte scintigraphy is indicated to detect infection, except if PCP is suspected. In patients who have known tumor and fever, 111In leukocyte imaging may be preferred to gallium imaging to identify a source of infection. Most fevers in these patients appear to be due to tumor and chemotherapy, which would not manifest as an area of abnormality on an 111In leukocyte scan. If localizing symptoms are present, CT may be the preferred technique. The major concerns about 111In leukocytes are the hazards associated with withdrawal of blood, handling of blood, and reinjecting labeled cells and the requirement to delay imaging for 18 to 24 hours, thus precluding a rapid result. Potential replacement agents for 111In leukocytes include labeled immunoglobulins and labeled antigranulocyte antibody agents. The three- or four-phase bone scan is the first line diagnostic imaging technique after a plain radiograph in the evaluation of suspected osteomyelitis. If the bone scan is inconclusive, 111In leukocytes are the second line diagnostic imaging technique, particularly in adults with other bony abnormalities such as degenerative bone changes or trauma. Gallium imaging also may be used, preferably if other bony abnormalities are absent. In children, gallium imaging is the second line diagnostic imaging technique. Once the diagnosis has been made, gallium may be the preferred technique for following response to therapy.
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PMID:Radionuclide imaging in the evaluation of infections and inflammatory disease. 833 67

This review summarises mutagenesis-related research on the major classes of DNA minor groove binding ligands. These compounds can bind to DNA covalently or non-covalently, and span a range of DNA sequence selectivities. Many of the non-covalent binders show effects on topoisomerase enzymes in mammalian cells, with the bisbenzimidazoles being the most active. Mutagenic effects consistent with topoisomerase inhibition are observed in vitro. Many of these compounds induce aneuploidy and polyploidy, properties which may also contribute to carcinogenic processes. Similarly, uvrA trapping by some minor groove binders may alter mutagenetic processes by inhibiting efficient repair. Distamycin has been shown to enhance the mutagenicity of ethidium bromide in bacteria by an undetermined mechanism. However, the inhibitory effects of minor groove binders on human DNA repair systems have not yet been reported. Hoechst 33258 and distamycin cause chromosome decondensation in both mouse and human cells particularly at heterochromatic regions which are rich in AT content. Various minor groove binders have been shown to induce fragile sites in cultured lymphocytes from susceptible individuals, which may have a propensity to develop particular cancers. Investigation of the relationship between fragile site inducing drugs and chromosomal rearrangements in fragile site carriers has not been investigated but may yield interesting results. Some DNA alkylating minor groove binders can generate lesions extremely toxic to mammalian cells (e.g., CC-1065 and analogues), and induce a range of DNA sequence changes in vivo, both at the site of covalent bonding as well as at surrounding sequences. This may be typical of alkylating minor groove binders which have a binding site size of several base pairs, and which stabilise helical structure. Minor groove binders have effects on gene expression in vitro by inhibiting the sequence selective binding of various transcription factors to DNA. These effects may result in expression or repression of downstream genes also. This class of ligand thus offers the possibility of mutations targeted to specific genes or genomic regions. It will be interesting to determine whether such examples of targeted mutagenesis, as has already been observed with CC-1065 and adozelesin, will result in an enhanced or in a lowered capacity to promote neoplastic disease. However it should be noted that pentamidine, a minor groove binder used in the treatment of AIDS-related PCP, has thus far shown no mutagenic effects in nuclear DNA and only a weak effect in mitochondrial DNA of yeast. These results suggest that minor groove binding does not necessarily lead to mutagenesis.
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PMID:The mutagenic properties of DNA minor-groove binding ligands. 878 82

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

WNT signals play key roles in carcinogenesis and embryogenesis through the specification of cell fate and polarity. Dishevelled (DVL) proteins are WNT signaling molecules implicated in beta-catenin pathway and PCP pathway. Xenopus Dapper and Frodo are Dvl-binding proteins, showing 89.8% total-amino-acid identity. Here, we identified and characterized human homologs of Xenopus Dapper and Frodo using bioinformatics. Human DAPPER1 gene was located within human genome draft sequence NT_025892.9 (nucleotide position 39378960-39387891 in the forward orientation), and human DAPPER2 gene within NT_007302.10 (nucleotide position 660279-672480 in the reverse orientation). DAPPER1 (799-amino-acids) and DAPPER2 (774-amino-acids) showed 28.8% total-amino-acid identity. Seven DAPPER homologous (DAPH) domains, including DAPH2 (leucine zipper), DAPH3 (serine rich) and DAPH7 (PDZ binding), were conserved between DAPPER1 and DAPPER2. Phylogenetic analysis of vertebrate Dapper proteins revealed that Xenopus Dapper and Frodo are orthologs of human DAPPER1. DAPPER1 mRNA was expressed in amnion, fetal brain, eye, heart, adult brain medulla, gastric cancer (signet ring cell features), RER+ colon tumor, acute lymphoblastic leukemia, germ cell tumor, chondrosarcoma, and parathyroid tumor. DAPPER2 mRNA was expressed in placenta, genitourinary tract tumor, and endometrial adenocarcinoma. DAPPER1 and DAPPER2 genes were mapped to human chromosome 14q22.3 and 6q27, respectively. Human chromosome 14q22.3 is deleted in astrocytoma, while human chromosome 6q27 is deleted in breast, ovarian, and gastric cancer. Based on evolutionary and functional conservation of WNT signaling molecules as well as human chromosomal localization, DAPPER1 and DAPPER2 genes are predicted to be potent cancer-associated genes.
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PMID:Identification and characterization of human DAPPER1 and DAPPER2 genes in silico. 1263 86

TCHQ is a major carcinogenic metabolite of the widely used wood preservative PCP. Recently, we found that TCHQ was a promoter in a mouse skin carcinogenesis model. However, the mechanism is still not clear. In this study, we showed that overexpression of Bcl-2 effectively suppressed TCHQ-induced apoptosis in NIH3T3 cells, as evidenced by morphological changes and DNA fragmentation. Although production of ROS contributes to TCHQ-induced apoptosis, Bcl-2 failed to attenuate TCHQ-elicited increase of intracellular ROS level. In addition, overexpressed Bcl-2 provides only partial protection against TCHQ-induced cellular DNA damage. We also found that TCHQ induced a change in mitochondrial transmembrane potential, and that caspase-9 and subsequent caspase-3 can be activated during TCHQ-induced acute apoptosis. Interestingly, TCHQ induced a significant upregulation of Bcl-2 expression, and over-expressed Bcl-2 can dramatically inhibit the change of mitochondria membrane potential and activation of both caspase-9 and -3. Thus, our results suggest TCHQ-induced tumor promotion may be through a mechanism of upregulation of Bcl-2 protein and subsequent apoptosis inhibition.
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PMID:Bcl-2 overexpression inhibits tetrachlorohydroquinone-induced apoptosis in NIH3T3 cells: a possible mechanism for tumor promotion. 1510 27

The goal of this study is to present the clinical and evolutive features of Pneumocystis infection (PCP) in infants admitted in our clinic. We summarise these aspects from 17 cases (10 male and 7 female infants), admitted between 1st January 2004 and 31st May 2005. PCP infection is rare. It represents 1,5/1000 children (17 cases of 11328 total patients) admitted in our hospital. The risk factors for PCP were age between 6 weeks and 6 months (average 3,38 months) low birth weight (average = 2428 grams), low weight for age, prolonged hospital admission (88,23% of the 17 infants were abandoned in nursery). Only one of them had HIV infection and none presented neoplastic disease. The most prominent clinical aspect was tachypnea (average 78 breath/minute, maximum 130). 16 (94,11%) had difficult breathing with chest in-drawing and flaring of ala nasi. 14 (82,35%) had generalised cyanosis. Only two (11,72%) infants had fever. Radiologic aspects were evocative, with diffuse pulmonary involvement in almost all cases (88,23%). 6 infants (35,29%) had pneumothorax and 2 (11,76%) presented pneumomediastinum. Positive diagnosis was made by microscopic examination of secretions from endotracheal tube aspiration (Grocott methenamine silver stain and Romanowsky stain). 14 infants were ventilated with a good outcome--12 surviving infants (85,7%). All infants had a full course of intravenous Co-trimoxazole. The deceased infants had more risk factors--congenital heart disease 1 case, severe cerebral palsy with organic epilepsy 2 cases. The apparent increase of PCP cases can be related to the number of abandoned children in Romanian pediatric hospitals and nurseries.
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PMID:[Pneumocystis pneumonia in infants]. 1653 25


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