Analysis of the promoter region of the CHO APRT gene.
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Adenine Phosphoribosyltransferase↗
Biomedical subjects
M W Taylor
Publications and source records attributed to M W Taylor.
A dual anti-tumor effect of a combination of interferon-alpha and 5-flurouracil or 2-chlorodeoxyadenosine on natural killer (NK) cell mediated cytotoxicity.
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2-Chloroadenosine↗
Analysis of interferon-gamma resistant mutants that are possibly defective in their signaling mechanism.
Our previous observations indicated that mutants partially resistant to IFN-gamma cytotoxicity were defective in the induction of indoleamine 2,3-dioxygenase, (IDO). Two mutants highly resistant to IFN-gamma were isolated following a second round of mutagenesis. The resistance to IFN-gamma was inversely correlated with the inducibility of IDO in these mutants. Moreover, several other IFN-gamma responsive genes, including those encoding 2-5A synthetase, GTP cyclohydrolase and HLA-DR alpha, were also differentially altered in their expression upon INF-gamma treatment. IFN-gamma receptor gene expression was not changed nor was the binding of the receptor to IFN-gamma. Southern blot analysis failed to reveal any significant abnormality in the IDO gene structure in these mutants. We therefore suggest that these mutants are defective in the IFN-gamma signaling pathway and will be useful in further analysis of the biochemical mechanism of IFN-gamma activated gene expression in target cells.
Blotting, Northern↗
Transduction of the CHO aprt gene into mouse L cells using an adeno-5/APRT recombinant virus.
An adenovirus-5 recombinant virus Adapt1 carrying the Chinese hamster ovary (CHO) adenine phosphoribosyltransferase (aprt) gene was constructed by insertion of a 2.5-kb fragment containing the complete CHO aprt structural gene linked to a Moloney murine sarcoma virus (MSV) promoter into the E3 region of adenovirus-5. The CHO aprt gene was in the opposite orientation to the adenovirus E3 promoter. Mouse Lapt- tk- (LAT) cells expressed the CHO aprt gene when infected with the virus, even at low MOI (O.1). APRT activity was detectable from approximately 20 h postinfection. At a low frequency, LAT cells were transformed to aprt+, and four stable transductants were selected in adenine, azaserine (AA) medium. Such cells expressed APRT at approximately 50% wild-type activity and the enzyme was shown to be CHO APRT by starch gel electrophoresis. DNA was isolated from the transductants and probed with CHO aprt-specific DNA and with viral DNA probes. The results indicated that the CHO aprt gene was integrated into the LAT cells at a site other than mouse aprt. Although neighboring viral sequences were integrated and maintained in the transductants, viral sequences further upstream and downstream of the aprt gene were absent.
Adenine↗
Effects of extended hospitalization: a one-year follow-up study.
The C. F. Menninger Memorial Hospital is conducting an ongoing follow-up study of the effects of extended hospitalization. The authors report key indicators of outcome at one year postdischarge for 110 patients hospitalized on extended care units for at least 180 days. Outcome is determined by postdischarge rates of rehospitalization, postdischarge suicide attempts, and occupational functioning at the time of the one-year follow-up interview. After comparing these areas with preadmission levels of symptomatology and functioning, the authors report significant improvement in each category at the time of follow-up.
Adaptation, Psychological↗
Relationship between interferon-gamma, indoleamine 2,3-dioxygenase, and tryptophan catabolism.
Interferons have been shown to be potential anti-cancer agents and to inhibit tumor cell growth in culture. The in vivo mechanism of the anti-proliferative effect may be direct or indirect through the immune system; however, in vitro a primary mechanism of cytotoxicity is through the depletion of tryptophan. In particular, interferon-gamma (IFN-gamma) induces an enzyme of tryptophan catabolism, indoleamine 2,3-dioxygenase (IDO), which is responsible for conversion of tryptophan and other indole derivatives to kynurenine. The inhibitory effect of interferon on many intracellular parasites such as Toxoplasma gondii and Chlamydia trachomatis is by the same mechanism. Elevated kynurenine levels have been found in humans in a number of diseases and after interferon treatment, and the enzyme is induced in rodents after administration of interferon inducers, or influenza virus. IDO induction also occurs in vivo during rejection of allogeneic tumors, indicating a possible role for this enzyme in the tumor rejection process. The gene for IDO has been cloned and shown to be differentially regulated by IFN-alpha and IFN-gamma. IDO induction has been correlated with induction of GTP-cyclohydrolase, the key enzyme in pteridine biosynthesis. A direct role for IDO in pteridine synthesis has not been shown, and this parallel induction may reflect coordinate regulation of genes induced by IFN-gamma. A possible role for IDO in O2-radical scavenging and in inflammation is discussed.
Animals↗
Cure with low-dose total-body irradiation of the hematological disorder induced in mice with the Friend virus: possible mechanism involving interferon-gamma and interleukin-2.
The effects of split low-dose total-body irradiation (TBI; 150 cGy) on production of interferon (IFN)-gamma and Interleukin-2 (IL-2) and on the growth characteristics of erythroid progenitor cells (BFU-E) have been assessed in normal mice, normal mice receiving TBI only, mice infected with the polycythemia-inducing strain of the Friend virus complex (FVC-P), and FVC-P infected mice receiving 150 cGy TBI on days 5 and 12. It was found that lymphocytes from the spleens of TBI-treated mice previously infected with FVC-P produced in response to phytohemagglutinin (PHA) and concanavalin A (Con A) stimulation up to 15 times greater amounts of IFN-gamma than cells from untreated FVC-P-infected mice. IL-2 production in Con A-stimulated spleen cell cultures also increased when cells were isolated from FVC-P-infected mice treated by low-dose TBI compared to untreated FVC-P-infected mice. TBI treatment was associated with greater than 99% ablation of "erythropoietin-independent" BFU-E colony formation. The results suggest that the cure of FVC-P-infected mice by low-dose TBI may result from activation of the IFN-gamma system and IL-2 production.
Animals↗
An assessment of computing activity by GPASS users in Scottish general practice.
The electronic questionnaire has been developed as a means of collecting data held on computers in Scottish General Practices using the standard national general practice computer system (GPASS). In 1989, data were gathered from 251 computerised Scottish practices using a floppy disc based interrogation program, amalgamated and then analysed. The results of this study are presented and examined in three separate ways: by region, by date of initial computerisation, and by list size per general practitioner (GP).
Computer Systems↗
The state of general practice computing in Scotland and the characteristics of computerised practices: a survey of 948 practices.
A survey of 1,179 Scottish practices produced an 81% response rate and gathered data about practice size, environment, state of computerisation as well as future plans for the use of computers in the practice. Results show that the majority of practices are already computerised and that over 90% will be computerised soon. A computer in the practice correlates especially with the presence of a practice manager, a practice nurse and training or teaching status. Scotland is unique in having a national software program (GPASS) for general practice administration. We estimate that by mid 1991 over 750 practices will be using GPASS.
Computers↗
General practice computing in Scotland.
OBJECTIVE: To investigate a method of assessing the extent of routine patient data held on computer by Scottish general practitioners. DESIGN: An "electronic questionnaire" in the form of an interrogation questionnaire was used to extract a subset of data from practice computers running a standard software package (the general practice administrative system for Scotland, GPASS). The data were retained by each practice and also collected and analysed centrally to produce regional and national data. SUBJECTS: All 257 general practices in Scotland using GPASS software were sent the electronic questionnaire; data from 154 practices, including 759 general practitioners and covering 1,010,452 patients, were collected. RESULTS: Ninety three practices had all their patient records on computer; others had selectively entered data on, for example, only those patients receiving repeat prescriptions. The number of computerised patient records per practitioner ranged from 46 to 2373. Altogether 194,261 patients had repeat prescribing data and 204,005 morbidity or clinical data. CONCLUSION: An electronic questionnaire is a simple and effective way of investigating the information held on practice computers, allowing analysis and feedback of information to practitioners. Development of this system will provide a cumulative information system for Scottish general practitioners.
Computers↗
Fever induced by Escherichia coli or intrahypothalamic prostaglandin E2 enhances interferon-gamma synthesis.
We previously showed that hyperthermia induced in rhesus monkeys (Macaca mulatta) by forced passive heating "primes" the peripheral lymphocyte population for increased synthesis of interferon-gamma (IFN-gamma). It was not clear whether these data could be extrapolated to the physiological response in naturally occurring fever. Therefore, in the current experiments, the temperature of rhesus monkeys was raised either by systemic injection of killed Escherichia coli or by intrahypothalamic administration of prostaglandin E2. Mononuclear cells collected subsequently from such monkeys produced more IFN-gamma in response to stimulation with mitogens than cells from control monkeys. Direct administration of IFN-alpha, -beta, or -gamma to the hypothalamus did not affect the body temperature of rhesus monkeys.
Animals↗
Specific effect of interferon on the herpes simplex virus type 1 transactivation event.
Human recombinant gamma interferon and to a lesser extent alpha interferon were shown to inhibit herpes simplex virus type 1 replication in the human cell lines WISH and HEp-2. Dot blot analysis of viral DNA synthesis and viral RNA transcription indicated that the inhibition occurred at an early step in infection. A study of the early events after herpes simplex virus type 1 infection indicated that adsorption, penetration, uncoating, and transport of viral DNA were not affected by interferon. Northern (RNA) blot analysis revealed that both immediate-early and delayed-early gene transcription was inhibited by interferon. Transactivation of the immediate-early responsive element linked to a reporter gene (CAT or tk) was specifically inhibited by both classes of interferon. Our data would indicate that either the transactivating protein VP16 or the complex formed between VP16 and a host protein(s) is attenuated by interferon.
Animals↗
Transcriptional activation of the adenine phosphoribosyltransferase promoter by an upstream butyrate-induced Moloney murine sarcoma virus enhancer-promoter element.
It has been documented that the activity of a specific promoter can be occluded by the presence of another promoter element upstream. We present evidence for a phenomenon contradictory to that predicted by the promoter occlusion theory. Transcription from the hamster aprt (adenine phosphoribosyltransferase) promoter was augmented instead of repressed in transfected mouse L cells when an upstream Moloney murine sarcoma virus enhancer-promoter element was induced with butyrate. Without an adjacent Moloney murine sarcoma virus element, butyrate could not activate the aprt promoter.
Adenine Phosphoribosyltransferase↗
Outcome at discharge for patients in an ongoing follow-up study of hospital treatment.
Methodological and practical difficulties have limited the growth of knowledge about outcome of psychiatric hospital treatment. The authors report on outcome at hospital discharge for 103 long-term and 93 short-term patients treated at the C. F. Menninger Memorial Hospital, part of an ongoing follow-up study of hospital treatment. Discharge outcome is based mainly on ratings of symptoms, global functioning, and therapeutic alliance as well as on patients' reports of satisfaction. At discharge both long- and short-term patients were found to have low levels of symptoms (based on the Brief Psychiatric Rating Scale) and a relatively adequate level of functioning (in the 51-to-60 range on the Global Assessment Scale) and to have been highly satisfied with treatment.
Adult↗
Trans-activation of herpes simplex virus type 1 immediate early genes is specifically inhibited by human recombinant interferons.
The effect of human recombinant interferons (IFNs) alpha and gamma on the transcription of Herpes Simplex virus type-1 (HSV-1) immediate early (IE) genes has been studied. Human amniotic cells (WISH) were transfected with a chimaeric plasmid containing the regulatory region of the HSV-1 IE genes controlling the expression of a reporter gene (CAT). Subsequently cells were infected with live HSV-1 to trans-activate the IE sequences. When cell samples were treated with IFN alpha or IFN gamma prior to viral infection, transcription of the CAT gene was greatly inhibited.
Amnion↗
An analysis of 5' regulatory sequences of the hamster APRT gene.
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Adenine Phosphoribosyltransferase↗
Effect of alterations of the ATG translation start codon of the APRT gene.
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Adenine Phosphoribosyltransferase↗
Detection of fibronectin on vascular flow surfaces by enzyme-linked immunosorbent assay.
Numerous variables are involved in the attachment of endothelial cells to a substrate. Quantifying these factors both on native vessels and on synthetic substrates is important in determining the success of endothelial cell attachment, retention, and growth on these substrates. Fibronectin is an important cell attachment molecule and is likely to be key to the successful attachment of endothelial cells to any substrate. For this reason we have developed an enzyme-linked immunosorbent assay for interrogation of the luminal surface of native and synthetic vessels for the presence of fibronectin. A plexiglass chamber was designed with two blocks, an upper block with wells and a lower supporting block. The chamber was then assembled with a vessel between the two blocks, forming the bottom of the well. This luminal surface was then interrogated by conventional enzyme-linked immunosorbent assay. Native vessels, collagenase-digested vessels, acellular matrices and PTFE preclotted with whole blood were assayed to determine the quantity of fibronectin present. These results were correlated with a bioassay developed to determine the quantity of fibronectin necessary for cell attachment. It was concluded that all of the samples assayed had ample fibronectin for cell attachment and that other factors must be responsible for successful maintenance of a cell monolayer.
Acid Phosphatase↗