Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The case notes of patients with blood cultures positive for enterobacteriaceae were examined retrospectively over a 6-month period in Parirenyatwa Hospital, Harare, Zimbabwe. Speciation was possible for Salmonella typhi and shigellae only. Nontyphoidal salmonellae were serotyped. Salmonella or shigella bacteremia was identified in 51 patients. There were 14 isolates of S. typhi, 32 isolates of nontyphoidal salmonellae, and 5 isolates of shigellae species. The case notes of 38 patients could be identified for review, and of these HIV serology was available for 15 seropositive and 15 seronegative patients. The male to female ratio was approximately 3:1 for both groups and the mean age was 29.7 +or- 21. Nontyphoidal bacteremias as compared with typhoid fever were strongly associated with HIV seropositivity [p 0.01]. 3 out of 8 HIV-negative patients with nontyphoidal bacteremia had another underlying immunosuppressive disease [2 had myeloma and 1 patient had cirrhosis with complicating hepatoma]. 2 patients with nontyphoidal bacteremia whose HIV status was unknown also had another immunosuppressing disease [acute myeloid leukemia and idiopathic pancytopenia]. 13 out of 15 HIV-positive patients showed other signs of HIV infection [oral candida, herpes zoster, persistent generalized lymphadenopathy]. 3 out of 11 patients [27%] with typhoid died, while 11 out of 27 patients [40.7%] with nontyphi bacteremia died. Most strains of S. typhimurium were included in serogroup B, which accounted for 37% of nontyphoidal isolates. Earlier studies identified invasive salmonellosis in patients with other AIDS defining diseases. In Nairobi clinical features of HIV infection were found in 64% of bacteremic HIV-positive patients, but only 28% of patients fulfilled the CDC clinical case definition for AIDS. A more recent study from Nairobi demonstrated that S. typhimurium bacteremia is a common cause of intercurrent infection in HIV-positive tuberculous patients.
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PMID:Salmonella and shigella bacteraemia in Zimbabwe. 813 Nov 97

We have developed a procedure to purify the recombinant fusion toxin IL6-PE4E from Escherichia coli which results in a high yield of fully active monomeric protein of high purity and very low endotoxin content. The chimeric toxin is composed of human interleukin 6 (IL6) fused to a derivative of Pseudomonas exotoxin (PE) containing mutations in the binding domain which prevent binding to the PE receptor. In a typical preparation, 20 g of E. coli cells expressing the plasmid encoding IL6-PE4E were treated with lysozyme and washed repeatedly with detergent (Triton X-100), to obtain 500 mg of inclusion bodies. The recombinant protein was denatured and reduced in guanidine hydrochloride solution containing dithioerythritol and refolded in a redox buffer containing oxidized glutathione and L-arginine. After purification of the dialyzed protein by anion-exchange, polymyxin B, and sizing chromatography, we obtained 100 mg (20% of recombinant protein) of purified monomer with 0.6-2.5 endotoxin units/mg of protein. Amino terminal sequencing confirmed the first 20 amino acids. IL6-PE4E purified in this manner was fully cytotoxic toward human multiple myeloma, hepatoma, epidermoid carcinoma, and prostate carcinoma cell lines. After intravenous injection into mice, we found the dose-limiting toxicity to be to the liver, by measurement of serum transaminases and histologic evaluation of the liver. The LD50 was 450 micrograms/kg. We conclude that IL6-PE4E can be purified efficiently for preclinical testing.
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PMID:Purification and characterization of IL6-PE4E, a recombinant fusion of interleukin 6 with Pseudomonas exotoxin. 830 30

Overexpression of the transmembrane protein-tyrosine phosphatase (PTPase) CD45 in nonhematopoietic cells results in decreased signaling through growth factor receptor tyrosine kinases. Consistent with these data, insulin receptor signaling is increased when the CD45-related PTPase LAR is reduced by antisense suppression in a rat hepatoma cell line. To test whether the hematopoietic cell-specific PTPase CD45 functions in a manner similar to LAR by negatively modulating insulin receptor signaling in hematopoietic cells, the insulin-responsive human multiple myeloma cell line U266 was isolated into two subpopulations that differed in CD45 expression. In CD45 nonexpressing (CD45-) cells, insulin receptor autophosphorylation was increased by 3-fold after insulin treatment when compared to CD45 expressing (CD45+) cells. This increase in receptor autophosphorylation was associated with similar increases in insulin-dependent tyrosine kinase activation. These receptor level effects were paralleled by postreceptor responses. Insulin-dependent tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1) and Shc was 3-fold greater in CD45- cells. In addition, insulin-dependent IRS-1/phosphatidylinositol 3-kinase association and MAP kinase activation in CD45- cells were also 3-fold larger. While expression of CD45 was associated with a decrease in the responsiveness of early insulin receptor signaling, interleukin 6-dependent activation of mitogen-activated protein kinase kinase and mitogen-activated protein kinase was equivalent between CD45- and CD45+ cells. These observations indicate that CD45 can function as a negative modulator of growth factor receptor tyrosine kinases in addition to its well-established role as an activator of src family tyrosine kinases.
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PMID:The transmembrane protein-tyrosine phosphatase CD45 is associated with decreased insulin receptor signaling. 855 83

An inhibitor of IL-6 binding to the human hepatoma line HepG2 and myeloma cell line U266 was identified in a saline extract of the marine sponge, Callyspongia sp. Functional activity, measured through the increase in haptoglobin production by HepG2 cells stimulated with IL-6, could be strongly inhibited by the extract. Similarly, IL-6-induced production of IgM by the B cell line SKW6.4 was substantially reduced. In neither cell line was there evidence of toxicity produced by the extract. Other sponges of the Callyspongia species were found to contain analogous activity. The activity was destroyed by trypsin treatment or boiling of the extract, suggesting that the inhibition is due to a protein. When the binding of IL-6 to its receptor complex was dissected in vitro, inhibition of binding of IL-6 to soluble receptor by the extract was not detected, but binding of the IL-6-sIL-6R complex to soluble gp130 was inhibited in a dose-dependent fashion. This was borne out in cellular assays since the extract inhibited activation of HepG2 cells stimulated with oncostatin M or leukemia inhibitory factor, cytokines which also use gp130 for signal transduction. These results suggest that the Callyspongia extract contains a protein which blocks the interaction of the IL-6 family of cytokines with their signal transduction moiety, gp130. Elucidation of the structure and mode of action of such a protein would be helpful in designing gp130 antagonists to inhibit the functions of this cytokine family, overproduction of which has been associated with cancer and pathologies of autoimmune disease and AIDS.
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PMID:Characterization of an interleukin 6 cytokine family antagonist protein from a marine sponge, Callyspongia sp. 863 42

Hepatitis C virus (HCV) is a major worldwide cause of acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The development of vaccines against HCV have been complicated by the high variability of the envelope region, and it is likely that the cellular immune responses to viral structural proteins may be important for eradicating persistent viral infection. Recently, it was reported that the injection into muscle cells of plasmids encoding viral genes resulted in the generation of strong cellular immune responses. We constructed vectors that express the highly conserved HCV core gene. In this regard, the pHCV 2-2 construct contained the entire HCV core region and pHCV 4-2 contained both the 5' noncoding region and the core gene. Cellular expression of HCV core protein was assessed following transfection into human and murine cell lines, and higher intracellular levels of the 21-kd core protein were observed with pHCV 2-2. These HCV core DNA constructs were used to immunize BALB/c mice and produced low-level anti-HCV core humoral immune responses. To assess cytotoxic T-lymphocyte (CTL) activity generated in vivo, a cloned syngeneic SP2/O myeloma cell line constitutively expressing HCV core protein was established and inoculated into BALB/c mice to produce growth of plasmacytomas. Strong CTL activity was generated because the tumor size and weight in pHCV 2-2-immunized mice were remarkably reduced compared with mice injected with mock DNA. Spontaneous CTL activity was also exhibited by splenocytes in an in vitro cytotoxicity assay. These investigations demonstrate that plasmid constructs expressing HCV core protein generate strong CTL activity, as assessed both in vivo and in vitro, and are promising candidates as antiviral agents.
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PMID:Expression and immune response to hepatitis C virus core DNA-based vaccine constructs. 870 53

The establishment of stable cell lines expressing the hepatitis C virus (HCV) core protein may be important for studies of HCV pathogenesis. Human and mouse cell lines were generated expressing the HCV core protein using expression vectors driven by either the cytomegalovirus (CMV) or elongation factor-1 alpha (EF-1 alpha) promoters. Following transient transfection, HCV core protein was expressed in all cell lines. However, stable human hepatocellular carcinoma (HCC) and murine myeloma cell lines expressing the HCV core protein were only established using constructs driven by the EF-1 alpha promoter. In contrast, stable expression of the hepatitis B virus (HBV) middle envelope protein (MHBs) was obtained successfully in these cell lines using an expression vector driven by the CMV promoter. Inhibitory activity of the first 69 amino acids of the HCV core protein on the CMV promoter was found by using chimeric MHBs/HCV core protein constructs. Growth of cloned cell lines expressing the HCV core protein was slower than that of nonexpressing cell lines. However, morphological changes and cell death were not observed in the stable cell lines expressing HCV core protein. These results indicate that the HCV core protein was not directly cytotoxic to HCC and myeloma cell lines but that specific promoter elements are required to establish stable expression of the nucleocapsid structural protein.
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PMID:Comparison between cytomegalovirus promoter and elongation factor-1 alpha promoter-driven constructs in the establishment of cell lines expressing hepatitis C virus core protein. 902 32

Our purpose was to identify the histologic types of malignant liver lesions with high signal intensity (SI) on T1-weighted images and to describe the MR imaging features. Thirteen patients with malignant liver lesions high in SI on T1-weighted images were studied with a 1.5-T MR imager using pre- and serial postcontrast spoiled gradient-echo (SGE) sequences (all patients), T2-weighted fat-suppressed spin-echo sequences (all patients), precontrast T1-weighted fat-suppressed spin-echo sequences (five studies in five patients), and precontrast out-of-phase SGE sequences (seven studies in six patients). Images were reviewed retrospectively to determine number of lesions; lesion size; SI of lesions on T1-weighted, T2-weighted, and fat-attenuated T1-weighted images; distribution of high SI in lesions on T1-weighted images; and tumor enhancement pattern. Seven patients had multiple tumors high in SI on T1-weighted images and six patients had solitary tumors. Seventy-two lesions were less than 1.5 cm in diameter and 35 lesions were more than 1.5 cm in diameter. Nine patients had solid malignant lesions and four patients had cystic malignant lesions. All tumors more than 1.5 cm in diameter were heterogeneously high in SI on T1-weighted images, and all tumors less than 1.5 cm were completely homogeneous or homogeneous with a small central hypointense focus. All tumors were more conspicuous on T1-weighted fat-attenuated images, both on excitation spoiled fat-suppressed spin-echo or on out-of-phase SGE images with the exception of one fat-containing hepatocellular carcinoma (HCC). In one patient with melanoma metastases and one patient with multiple myeloma nodules, appreciably more lesions were detected on out-of phase SGE images. Causes of hyperintensity were considered to be either fat, melanin central hemorrhage, or high protein content, all of which may be seen in a variety of tumors. Fat-attenuation techniques are helpful in the detection of these lesions.
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PMID:Malignant lesions of the liver with high signal intensity on T1-weighted MR images. 913 92

IL-6 is a pleiotropic cytokine and plays a major role in inflammation and in the immune response. Altered serum levels of IL-6 have been described in several pathologies such as myeloma, EBV-lymphoma and chronic autoimmune disease. Here we report data on the utilization of a hIL-6 receptor superantagonist with a gene therapy approach. The superantagonist used in this work possesses very high affinity for the hIL-6 receptor, and is therefore an excellent candidate for the treatment of IL-6-dependent diseases. To obtain an efficient in vivo delivery method, we constructed a recombinant adenovirus expressing the IL-6 receptor superantagonist by inserting the cDNA, controlled by the RSV promoter, into a first generation replication-incompetent adenoviral vector. Recombinant virus allowed correct expression of the transgene in vitro. Supernatants of infected cells specifically inhibited IL-6-induced transcriptional activation in hepatoma cells and blocked the IL-6-dependent proliferation of human myeloma cells. After intravenous injection of the recombinant virus into mice, nanomolar amounts of antagonist were produced in the serum, and these were able completely to inhibit IL-6 bioactivity. Gene transfer of such an antagonist offers a practical means of imposing long-term blockade of IL-6 activity in vivo for investigational and therapeutic purposes.
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PMID:Adenovirus-mediated gene transfer of a human IL-6 antagonist. 933 13

A high-dose bolus regimen for interleukin(IL)-2 administration to cancer patients frequently causes serious side-effects in which various organs are involved. In order to reveal the mechanism of toxicities associated with this regimen, we compared the augmenting effect of high-dose IL-2 on murine organ-associated lymphocytes between neoplastic and non-neoplastic states. Intraperitoneal administration of IL-2 at a dose of 10(5) JRU (Japanese Reference Units) twice daily for 3 days led to the death of all the syngeneic MH134-hepatoma- or X5563-myeloma-bearing mice, whereas it had no lethal effect on non-tumor-bearing mice. Histological and morphometric analyses demonstrated that tumor-bearing mice displayed more extensive infiltration of large granular lymphocytes and agranular lymphocytes in the liver and lungs than did the non-tumor-bearing mice. Large granular lymphocytes had the ultrastructural characteristics of lymphokine-activated killer cells. Lymphocytes often underwent extravasation into the interstitial space and exhibited local proliferation without causing any direct injury to apposed parenchymal cells. Flow-cytometric analysis of hepatic mononuclear cells demonstrated that IL-2-receptor-beta (IL-2R beta)-bearing lymphocytes, i.e., natural killer cells and intermediate CD3 cells, were increased in number in the neoplastic state before the IL-2 injection. The present study indicates that the tumor-bearing state increases the number of organ-associated IL-2R beta + lymphocytes, which are then greatly amplified by the challenge of high-dose IL-2, leading to the functional disturbance of organs. We have further demonstrated here that an intermittent low-dose IL-2 regimen has a potential therapeutic effect on tumor regression without causing lethal side-effects.
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PMID:The tumor-bearing state induces augmented responses of organ-associated lymphocytes to high-dose interleukin-2 therapy in mice. 939 Jan 96

A new human myeloma cell line, KMS-18, was established from a 58-year-old male with multiple myeloma associated with hyperammonemia. The original leukemic cells and established KMS-18 cells possessed several of the same chromosomal abnormalities, including add(1)(q32), add(10) (q24) and add(17)(p11). In addition, the KMS-18 cells showed novel t(4;14)(p16.3;q32.3) masked translocation which was determined by the FISH method. Moreover, we compared the ammonia production in culture medium of the KMS-18 cell line with that of non-myeloma hematological malignant cell lines and a hepatocellular carcinoma cell line. KMS-18 produced higher levels of ammonia in medium than the other cell lines examined. This new cell line may prove helpful in analyzing the role and biological mechanisms of the t(4;14)(p16.3;q32.3) translocation in myeloma and also in investigating hyperammonemia in cases with myeloma.
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PMID:Establishment of a new human myeloma cell line, KMS-18, having t(4;14)(p16.3;q32.3) derived from a case phenotypically transformed from Ig A-lambda to BJP-lambda, and associated with hyperammonemia. 947 91


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