Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Examination of P3HR-I cells (Epstein-Barr virus [EBV] producer) persistently infected with the MAL strain of herpes simplex virus type I (HSV-I) suggested that only a few cells were actively producing a virus indistinguishable from HSV-I (MAL) despite the presence of immunofluorescent HSV-I antigens associated with the majority of cells. EBV-specific immunofluorescence was not altered in HSV-I persistently infected P3HR-I cells. HSV-I persistently infected cells, labelled for 72 h with 14C-thymidine, incorporated approx. 8% of the label into cell associated HSV-I DNA as resolved by caesium chloride gradients. Values greater than 8% of the total were suggested by hybridization of gradient fractions with 3H-HSV-I DNA. To determine whether the establishment of HSV persistent infections in Burkitt lymphoma derived cells was a general phenomenon, six strains of HSV-I (MAL, KOS, Patton, Syn R, BF and SYN V) and two strains of type 2 (333 and MS) were used to infect the P3HR-I and Raji (EBV non-producer) cell lines derived from Burkitt lymphomas. In P3HR-I cells, persistent infections were established with all strains of HSV-I but not with HSV-2. In Raji cells, persistent infections were established with all strains of HSV-I, except Syn V, and with both strains of HSV-2. No external support was required to maintain these infections.
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PMID:Persistent herpes simplex virus infections established in two Burkitt lymphoma derived cell lines. 18 14

A somatic cell hybrid (Cl. 6d) was originated from the fusion of mouse 3T3-4E) and spontaneous yielder SV 40-transformed Chinese hamster (CHK/SVLP AG) cells. During the early stages of its history, the C1. 6d hybrid underwent a rapid chromosome loss, preferentially loosing hamster chromosomes. This was not a constant tendency of the hybrid cells. As the parental CHK)SVLP AG cells, the hybrid cells were always found 100 per cent SV40 T-antigen positive. While CHK/SVLP AG cells infectious SV 40 DNA, V-antigen and virus were regularly detected, in the hybrid cells only infectious DNA was occasionally detected. This was not due either to the loww of an essential Chinese hamster gene(s) or to the presence of an inhibiting mouse cell component(s); it was apparently the consequence of inability of the cells to properly activate the resident SV 40 genome(s). After superinfection with SV 40 DNA, the hybrid cells-though capable of synthesizing SV 40 V-antigen--were unable to ensure virus assembly. Experimental evidence was obtained suggesting that SV 40 maturation is dependent of a cellular function(s).
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PMID:Expression of "early" and "late" viral functions in a somatic cell hybrid between a mouse cell and a spontaneous yielder SV 40-transformed Chinese hamster cell. 20 68

DNA polymerase gamma from purified nuclei of EMT-6 cells (mice) seems to be identical to the mitochondrial DNA polymerase from the same source following several criteria. These two enzyme activities are strongly inhibited by ethidium bromide and acriflavin, while proflavin, acridine orange, daunomycin and chloroquine inhibition is less pronounced. In the case of DNA polymerases alpha and beta very little inhibition by ethidium bromide was observed. Intercalation of this dye in a poly dA-dT 12-18 template-primer was studied spectrophotometrically under conditions similar to those in the in vitro DNA polymerase assay. The polymerase assay. The inhibition by this drug of the mitochondrial DNA polymerase gamma activity was shown to be competitive at varying concentrations of TTP while the inhibition was of the non-competitive type at different concentrations of poly dA-dT 12-18. We conclude that the drug, most probably in the intercalated form, is able to interact with the active site (s) of mitochondrial DNA polymerase.
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PMID:The inhibition of mitochondrial DNA polymerase gamma from animal cells by intercalating drugs. 67 50

Potorous tridactylis (PTK2) cells growing in culture were treated with psoralen derivatives and dividing cells were located by phase-contrast microscopy. Psoralens, light-sensitive DNA-photoadducting drugs, were reacted with mitotic chromosomes through exposure to 365-nm light from an argon laser microbeam system. It was found that following mitosis and photoreaction, cells without nuclear envelopes were produced when psoralen-treated cells received 60 light pulses over their entire chromosome complement. These 'non-nuclear membrane' cells were found to incorporate [3H]uridine and, to a lesser extent, [3H]thymidine by autoradiography. Reduction of the light exposure by half (30 near-u.v. pulses) over the entire chromosome complement in the presence of psoralen also produced non-nuclear-membrane cells as seen by light microscopy. Further examination of these cells (30 light pulses) by single-cell electron microscopy revealed that unlike the high light exposure (60 near-u.v. pulses), the low light dosage resulted in cells with membrane patches associated with their chromatin. Since neither actinomycin D nor cycloheximide impeded nuclear envelope reformation, the psoralen-DNA reaction is concluded to produce non-nuclear-membrane cells by a mechanism other than transcription or translation inhibition. The association of Golgi with areas of nuclear membrane patches gives indirect evidence of a possible Golgi contribution to the reformation of the nuclear envelope after mitosis. It is concluded that DNA plays a role in envelope reformation.
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PMID:Chromatin influence on the function and formation of the nuclear envelope shown by laser-induced psoralen photoreaction. 70 93

The light-activated, nucleic acid-binding drugs, psoralens, were used in conjunction with a 365-nm laser microbeam to selectively bind to any nucleic acids in the centriolar region. 4'-aminomethyl-4,5',8--trimethyl-psoralen (AMT) has a high affinity for both RNA and DNA and can be shown to cause mitotic abortion when centriolar regions of prophase PTK2 cells and reacted with AMT and 365-nm laser light. Other psoralen derivatives which have a high affinity for DNA and a low affinity for RNA are not effective in blocking mitosis in dividing PTK2 cells. Examination of psoralen-bound centriolar regions by single-cell electron microscopy shows that at various times after treatment, the number of microtubules associated with the irradiated poles is much lower than in normal, dividing cells. Light-activated psoralen binding of the centriolar regions does not seem to affect the condensation or structure of mitotic chromosomes. It is concluded that there is an RNA in the centriolar region that is responsible for the formation of the spindle in dividing cells.
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PMID:Evidence for centriolar region RNA functioning in spindle formation in dividing PTK2 cells. 74 44

Electron microscopic visualization of molecular hybrids formed in situ is feasible at the present time. It can be accomplished by two alternative approaches. In one, the in situ hybridization is carried out on ultrathin sections of target embedded in glycol methacrylate. In the other, whole cells are used for hybridization and they are subsequently prepared for electron microscopy. The choice of the method to be adopted depends on the type of target tissue. When there is a choice, the second approach seems preferable. Some of the important technical steps in the hybridization procedure, such as DNA denaturation in ultrathin sections, have been discussed and attention has been drawn to practical problems that may arise during the preparatory steps. Our light microscope experiments demonstrate that preparations made after glutaraldehyde fixation have a lower hybridization efficiency than those fixed with 3 : 1 methanol-acetic acid. Attempts are therefore being made to explore the possibility of using methanol-acetic acid for electron microscope in situ hybridization. First results of straight-forward fixation show that the preservation of nuclear structure may be fairly satisfactory for the purpose. However, the cumultative effects of subsequent treatments in the procedure still remain to be examined. For electron microscope autoradiograph (EM ARG) of hybridized preparations, the most suitable emulsion at present appears to be Ilford L4. Various factors conductive to optimum resolution consistent with maximum efficiency in this emulsion have been pointed out. Practical problems that may arise in autoradiographs of hybridized preparations such as background and variation of grain density in adjacent sections have also been considered.
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PMID:Molecular hybridization of RNA and DNA in situ" visualization at the electron microscope level. 94 30

The mechanism by which 2-ME acts as a macrophage-substitute for the induction of a primary PFC response to SRC in vitro was studied in macrophage-depleted mouse spleen cell cultures. 2-ME could replace macrophages only in FCS-supplemented cultures. Evidence is presented that the function of 2-ME is independent of residual macrophages. Neither normal nor macrophage-depleted spleen cell cultures from congenitally athymic nude mice supplemented with 2-ME, with or without FCS, could give rise to a primary in vitro anti-SRC immune response. 2-ME, at an optimal concentration of 10(-5) M, induced DNA synthesis in normal and macrophage-depleted spleen cells in both FCS-containing and serum-free cultures. The peak response occurred on day 3. The stimulation was accompanied by a polyclonal B cell activation to antibody secretion which was much more pronounced in FCS-containing than in serum-free cultures. Spleen cells from nude mice showed a weaker DNA stimulation than did cells from normal mice in FCS-containing cultures, and nearly no response under serum-free conditions. T cells obtained by a nylon column adherence method from normal mouse spleen cells showed good DNA synthetic responses in FCS-containing, but no response in serum-free cultures. These results show that 2-ME has weak mitogenic activity for B cells, and in combination with FCS, strong mitogenic activity for T cells. Since the macrophage provides stimulation to the T cell in the primary anti-SRC PFC response in vitro, these results suggest that the direct mitogenic activity of 2-ME with FCS on T cells provides the functional substitution for macrophages.
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PMID:Function of 2-mercaptoethanol as a macrophage substitute in the primary immune response in vitro. 108 95

DNA histograms of exponentially growing EMT-6 cells in vitro were obtained at regular time intervals after exposure at 300 rads of x rays or one hour of heat shock at 43 degrees C. After either treatment, about 70% of the cells retained clonogenicity. Irradiation induced the expected block in the G2 + M phase, resulting in an increase of cells in that phase during the first 5 hours after exposure. Heat shock caused a block in both the S and G2 +M phases.
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PMID:Cell cycle progression of murine sarcoma cells after x irradiation or heat shock. 116 61

This report describes a clinical case of a large cell, immunoblastic plasmacytoid malignant B-cell lymphoma of the rectum in an AIDS patient coinfected with HTLV-I. The malignant cells showed clonal genetic rearrangement of the HC (JH) and LCK genes. Infection by EBV was demonstrated serologically and with slot blots using genomic DNA of the cancer cells. Southern blot analysis with DNA extracted from the lymphoma cells were negative for HTLV-I. The patient received seven cycles of VACO-B which induced complete but transient clinical remission of the tumor. The final outcome of the patient is unknown.
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PMID:Primary B cell lymphoma of the rectum in a patient coinfected with HIV-1 and HTLV-I. 128 27

The examination of the presence of Ph chromosome and of the fused gene BCR-ABL in patients with chronic myeloid leukemia (CML) is significant for the precise diagnosis and in some cases for the prognosis of the disease. We examined peripheral blood for the presence of BCR-ABL fused gene by polymerase chain reaction (PCR) in eight patients with CML consecutively cytogenetically studied before and after the bone marrow transplantation and in two patients treated with interferon. Southern blot analysis was performed before BMT in two patients and the molecular rearrangement of Ph chromosome was found. In all cases our results have proved that cytogenetic and recombinant DNA evaluations confirm each other. Due to the high sensitivity of PCR technique the minimal residual leukemia can be detected.
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PMID:[Use of cytogenetic and molecular biology in the detection of chronic myeloid leukemia]. 128 73


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