Biomedical subjects

J Guy

Publications and source records attributed to J Guy.

At least 19 recordsLinked to original sources

PubMed2004

High-energy particle acceleration in the shell of a supernova remnant.

A significant fraction of the energy density of the interstellar medium is in the form of high-energy charged particles (cosmic rays). The origin of these particles remains uncertain. Although it is generally accepted that the only sources capable of supplying the energy required to accelerate the bulk of Galactic cosmic rays are supernova explosions, and even though the mechanism of particle acceleration in expanding supernova remnant (SNR) shocks is thought to be well understood theoretically, unequivocal evidence for the production of high-energy particles in supernova shells has proven remarkably hard to find. Here we report on observations of the SNR RX J1713.7 - 3946 (G347.3 - 0.5), which was discovered by ROSAT in the X-ray spectrum and later claimed as a source of high-energy gamma-rays of TeV energies (1 TeV = 10(12) eV). We present a TeV gamma-ray image of the SNR: the spatially resolved remnant has a shell morphology similar to that seen in X-rays, which demonstrates that very-high-energy particles are accelerated there. The energy spectrum indicates efficient acceleration of charged particles to energies beyond 100 TeV, consistent with current ideas of particle acceleration in young SNR shocks.

Journal Article↗

PubMed2004

DNA sequence and analysis of human chromosome 9.

Chromosome 9 is highly structurally polymorphic. It contains the largest autosomal block of heterochromatin, which is heteromorphic in 6-8% of humans, whereas pericentric inversions occur in more than 1% of the population. The finished euchromatic sequence of chromosome 9 comprises 109,044,351 base pairs and represents >99.6% of the region. Analysis of the sequence reveals many intra- and interchromosomal duplications, including segmental duplications adjacent to both the centromere and the large heterochromatic block. We have annotated 1,149 genes, including genes implicated in male-to-female sex reversal, cancer and neurodegenerative disease, and 426 pseudogenes. The chromosome contains the largest interferon gene cluster in the human genome. There is also a region of exceptionally high gene and G + C content including genes paralogous to those in the major histocompatibility complex. We have also detected recently duplicated genes that exhibit different rates of sequence divergence, presumably reflecting natural selection.

Base Composition↗

PubMed2003

Drug errors: what role do nurses and pharmacists have in minimizing the risk?

A multi-professional project was carried out in order to identify the interventions that nurses and pharmacists make in relation to drug administration (an intervention refers to 'the process of querying a prescription with a prescriber'). The project highlights the importance of both these occupational groups in identifying prescribing errors and preventing them from being translated into actual medication errors. It also identifies the need for adequate training for nursing and medical staff, along with system changes, in order to minimize the risk of medication errors.

Drug Prescriptions↗

PubMed2001

Closely related proteins MBD2 and MBD3 play distinctive but interacting roles in mouse development.

MBD2 and MBD3 are closely related proteins with consensus methyl-CpG binding domains. MBD2 is a transcriptional repressor that specifically binds to methylated DNA and is a component of the MeCP1 protein complex. In contrast, MBD3 fails to bind methylated DNA in murine cells, and is a component of the Mi-2/NuRD corepressor complex. We show by gene targeting that the two proteins are not functionally redundant in mice, as Mbd3-/- mice die during early embryogenesis, whereas Mbd2-/- mice are viable and fertile. Maternal behavior of Mbd2-/- mice is however defective and, at the molecular level, Mbd2-/- mice lack a component of MeCP1. Mbd2-mutant cells fail to fully silence transcription from exogenous methylated templates, but inappropriate activation of endogenous imprinted genes or retroviral sequences was not detected. Despite their differences, Mbd3 and Mbd2 interact genetically suggesting a functional relationship. Genetic and biochemical data together favor the view that MBD3 is a key component of the Mi-2/NuRD corepressor complex, whereas MBD2 may be one of several factors that can recruit this complex to DNA.

Age Factors↗

PubMed2001

A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome.

Rett syndrome (RTT) is an inherited neurodevelopmental disorder of females that occurs once in 10,000-15,000 births. Affected females develop normally for 6-18 months, but then lose voluntary movements, including speech and hand skills. Most RTT patients are heterozygous for mutations in the X-linked gene MECP2 (refs. 3-12), encoding a protein that binds to methylated sites in genomic DNA and facilitates gene silencing. Previous work with Mecp2-null embryonic stem cells indicated that MeCP2 is essential for mouse embryogenesis. Here we generate mice lacking Mecp2 using Cre-loxP technology. Both Mecp2-null mice and mice in which Mecp2 was deleted in brain showed severe neurological symptoms at approximately six weeks of age. Compensation for absence of MeCP2 in other tissues by MeCP1 (refs. 19,20) was not apparent in genetic or biochemical tests. After several months, heterozygous female mice also showed behavioral symptoms. The overlapping delay before symptom onset in humans and mice, despite their profoundly different rates of development, raises the possibility that stability of brain function, not brain development per se, is compromised by the absence of MeCP2.

Animals↗

PubMed2001

Managing patient demand: a qualitative study of appointment making in general practice.

BACKGROUND: Managing patients' requests for appointments is an important general practice activity. No previous research has systematically observed how patients and receptionists negotiate appointments. AIM: To observe appointment making and investigate patients' and professionals' experiences of appointment negotiations. DESIGN OF STUDY: A qualitative study using participant observation. SETTING: Three general practices on Tyneside; a single-handed practice, a practice comprising three doctors, and a seven-doctor practice. METHOD: Participant observation sessions, consisting of 35 activity recordings and 34 periods of observation and 38 patient and 15 professional interviews, were set up. Seven groups of patients were selected for interview. These included patients attending an 'open access' surgery, patients who complained about making an appointment, and patients who complimented the receptionists. RESULTS: Appointment making is a complex social process. Outcomes are dependent on the process of negotiation and factors, such as patients' expectations and appointment availability. Receptionists felt that patients in employment, patients allocated to the practice by the Health Authority, and patients who did not comply with practice appointment rules were most demanding. Appointment requests are legitimised by receptionists enforcing practice rules and requesting clinical information. Patients volunteer information to provide evidence that their complaint is appropriate and employ strategies, such as persistence, assertiveness, and threats, to try and persuade receptionists to grant appointments. CONCLUSION: Appointment making is a complex social process where outcomes are negotiated. Receptionists have an important role in managing patient demand. Practices should be explicit about how appointments are allocated, including publishing practice criteria.

Adolescent↗

PubMed2000

Recombinant adeno-associated virus vector-based gene transfer for defects in oxidative metabolism.

Defects in oxidative metabolism may be caused by mutations either in nuclear genes or in mitochondrial DNA (mtDNA). We tested the hypothesis that recombinant adeno-associated virus (rAAV) could be used to complement mtDNA mutations. AAV vector constructs were designed to express the reporter gene encoding green fluorescent protein (GFP), fused to a targeting presequence that directed GFP to be translocated into mitochondria. These vectors mediated expression of mitochondrial-localized GFP, as indicated by fluorescence microscopy and electron microscopy, in respiring human embryonic kidney 293 cells and nonrespiring mtDNA-deficient (rho 0) cells. However, when sequences encoding hydrophobic segments of proteins normally encoded by mtDNA were inserted between the presequence and GFP, mitochondrial import failed to occur. In similar experiments, a fusion was created between pyruvate dehydrogenase (PDH) E1 alpha subunit, a nuclear-encoded mitochondrial gene with its own targeting presequence, and GFP. With this construct, expression of GFP was observed in mitochondria in vitro and in vivo. We conclude that the hydrophobicity of mtDNA-encoded proteins limits their ability to be transported from the cytoplasm. However, rAAV-based gene therapy may hold promise for gene therapy of PDH deficiency, the most common biochemically proven cause of congenital lactic acidosis.

Acidosis, Lactic↗

PubMed2000

Genomic sequence and transcriptional profile of the boundary between pericentromeric satellites and genes on human chromosome arm 10q.

The organization of centromeric heterochromatin has been established in a number of eucaryotes but remains poorly defined in human. Here we present 1025 kb of contiguous human genomic sequence which links pericentromeric satellites to the RET proto-oncogene in 10q11.2 and is presumed to span the transition from centric heterochromatin to euchromatin on this chromosome arm. Two distinct domains can be defined within the sequence. The proximal approximately 240 kb consists of arrays of satellites and other tandem repeats separated by tracts of complex sequence which have evolved by pericentromeric-directed duplication. Analysis of 32 human paralogues of these sequences indicates that most terminate at or within repeat arrays, implicating these repeats in the interchromosomal duplication process. Corroborative PCR-based analyses establish a genome-wide correlation between the distribution of these paralogues and the distribution of satellite families present in 10q11. In contrast, the distal approximately 780 kb contains few tandem repeats and is largely chromosome specific. However, a minimum of three independent intrachromosomal duplication events have resulted in >370 kb of this sequence sharing >90% identity with sequences on 10p. Using computer-based analyses and RT-PCR we confirm the presence of three genes within the sequence, ZNF11/33B, KIAA0187 and RET, in addition to five transcripts of unknown structure. All of these transcribed sequences map distal to the satellite arrays. The boundary between satellite-rich interchromosomally duplicated DNA and chromosome-specific DNA therefore appears to define a transition from pericentromeric heterochromatin to euchromatin on the long arm of this chromosome.

Centromere↗

PubMed2000

New therapies for optic neuropathies: development in experimental models.

Experimental models of human diseases have affected the design and direction of both basic and clinical research into understanding the pathogenesis and treatments of demyelinating disease, stroke, and hereditary disorders of the central nervous system. However, in spite of major advances in molecular research that have linked Leber Hereditary Optic Neuropathy to mutations in mitochondrial DNA, there has been relatively little focus in applying basic scientific methodologies to optic neuropathies other than glaucoma. The relative absence of detailed scientific knowledge about the basic mechanisms involved in the pathogenesis of optic nerve injury has contributed to the use of empiric therapies for neuro-ophthalmic optic neuropathies. Over the past decade major clinical trials, such as the Optic Neuritis Treatment Trial and Ischemic Optic Neuropathy Decompression Trial, have proven that currently available treatment options for demyelinating and ischemic optic neuropathies are ineffective and can even be harmful. Although the pathogenesis of visual failure in demyelinating, ischemic, and hereditary optic neuropathies appears diverse, a final common pathway for irreparable optic nerve injury may exist. This article reviews several models of experimental optic neuropathies that may aid in the development of novel treatments for neuro-ophthalmic disorders of the optic nerve during the 21st century.

Animals↗

PubMed1999

Adenoviral gene therapy with catalase suppresses experimental optic neuritis.

OBJECTIVE: To determine if adenoviral-mediated transfer of the gene for catalase (CAT), the reactive oxygen species scavenger, suppresses experimental optic neuritis. CLINICAL RELEVANCE: Gene therapy with CAT delivered by an adeno-associated viral vector was previously shown to suppress experimental optic neuritis. Because the transduction of protein expression with recombinant adeno-associated viral vector is relatively slow, taking weeks to reach full levels, we studied the effects of replication-deficient adenovirus containing CAT in suppressing experimental optic neuritis. Transduction with adenovirus occurs within days of inoculation, thus, it may be more applicable for the treatment of patients with acute optic neuritis. MATERIALS AND METHODS: Replication-deficient adenovirus containing CAT was injected above the right optic nerve heads of SJL/J mice that were simultaneously sensitized for experimental allergic encephalomyelitis. For controls, the left eyes were injected with the replication-deficient adenovirus without CAT or no virus. The histological effects of CAT on the lesions of experimental allergic encephalomyelitis were measured by computerized analysis of the myelin sheath area (for demyelination), optic disc area (for optic nerve head swelling), the extent of the cellular infiltrate, extravasated serum albumin labeled with immunogold (for disruption of the blood-brain barrier), and the in vivo hydrogen peroxide reaction product. RESULTS: After 1 month, cell-specific catalase activity, evaluated by the quantitation of catalase immunogold, was increased about 2-fold each in endothelia, oligodendroglia, astrocytes, and axons of the CAT-inoculated right optic nerves compared with the control left optic nerves. The increased cellular levels of catalase reduced demyelination by 30%, optic nerve head swelling by 25%, cellular infiltration by 26%, disruption of the blood-brain barrier by 61%, and in vivo levels of hydrogen peroxide by 81%. CONCLUSIONS: Adenoviral-mediated gene transfer increased catalase levels in all optic nerve cell types, and it persisted for 1 month after inoculation. The increased cellular levels of catalase suppressed demyelination and blood-brain barrier disruption at the foci in the optic nerve where prior magnetic resonance imaging and histopathologic studies have demonstrated the demyelinating inflammation of experimental and human optic neuritis. Together, they suggest that gene therapy with CAT may be helpful in the treatment of patients with optic neuritis.

Adenoviridae↗

PubMed1999

Treatment of paraneoplastic visual loss with intravenous immunoglobulin: report of 3 cases.

BACKGROUND: Paraneoplastic visual loss is an autoimmune disorder believed to be caused by the remote effects of cancer on the retina (cancer-associated retinopathy [CAR]) or optic nerve. Both disorders may result in rapid and complete blindness. Spontaneous recovery of vision has not been reported. The serum of patients with CAR contains autoantibodies against recoverin, enolase, or unidentified retinal proteins. Autopsy examination results of eyes of blind patients with CAR show complete absence of the retinal neurons involved in phototransduction. Corticosteroids and plasmapheresis are the only treatment options previously described. OBJECTIVE: To treat paraneoplastic visual loss. DESIGN AND METHODS: Three patients with metastatic cancer developed rapidly progressive loss of vision. The first patient had visual acuity of hand movements in each eye before intravenous immunoglobulin treatment. The second patient had visual acuity of light perception in both eyes. The third patient's visual acuity was 20/400 OD and 20/20 OS. Diagnostic tests included magnetic resonance imaging of the head and cytologic examination of the cerebrospinal fluid to exclude metastasis as the cause of visual loss and then an electroretinogram and serum tests for autoantibodies against retinal antigens to confirm the clinical diagnosis of CAR. Patients 1 and 2 were treated with intravenous immunoglobulin (400 mg/kg per day) for 5 days; however, patient 3 received only a single dose due to adverse effects consisting of shortness of breath and itching. RESULTS: Within 24 hours of taking the first dose of intravenous immunoglobulin, the visual acuity of patient 1 improved from hand movements only in both eyes to 20/50 OD and 20/200 OS. After the third day of treatment, visual acuity in the left eye further improved to 20/40. Even with the improved acuity, Goldmann visual field perimetry results showed poor responses in both eyes. However, 2 weeks later there was marked visual field improvement, and visual acuity was maintained at 20/50 OD and 20/40 OS. Patient 2 had no improvements and continued to have light perception in both eyes. Patient 3 had improvements in visual field defects but remained 20/400 OD and 20/20 OS. CONCLUSION: Intravenous immunoglobulin may be another treatment option offered to patients with paraneoplastic visual loss in addition to corticosteroids or plasmapheresis because a review of the medical literature has shown no spontaneous improvements of visual function without treatment.

Aged↗

PubMed1999

Reporter expression persists 1 year after adeno-associated virus-mediated gene transfer to the optic nerve.

OBJECTIVE: To determine the foci and duration of protein expression following virus-mediated gene transfer to the optic nerve. METHODS: A cytomegalovirus (CMV) promoter was linked to a lacZ-SV40 polyA reporter gene or a humanized green fluorescent protein (hgfp) reporter gene, then inserted into a bacterial plasmid containing adeno-associated virus (AAV) terminal repeat sequences. The CMV-lacZ or the CMV-hgfp construct were injected into the vitreous cavity of strain-13 guinea pigs. Controls consisted of eyes injected with AAV without the promoter and reporter elements or eyes that received no injections. The eyes and optic nerves were processed for beta-galactosidase immunohistochemistry and hgfp fluorescence analyses. Cellular transduction at the messenger RNA (mRNA) level was evaluated by in situ reverse transcription-polymerase chain reaction. RESULTS: Weekly fundus photography, done for 1 month, documented the absence of any ocular abnormality due to the viral injections. No in vivo hgfp fluorescence of the retina was visualized. Beta-galactosidase histochemical analysis of eye cups that received the lacZ gene construct showed blue lacZ staining of the optic nerve head at 2 weeks. Light microscopy revealed the blue beta-galactosidase reaction product in fibers, glial cells, and blood vessels of the optic nerve head and retrobulbar nerve. Histochemistry showed absence of beta-galactosidase in the optic nerve at 3 to 12 months, but immunochemistry showed the persistence of beta-galactosidase in fibers, glial cells, and blood vessels as late as 1 year after a single ocular injection. In the retina, histochemical staining showed evidence of lacZ at 3 months, but not later. In situ reverse transcription-polymerase chain reaction revealed brown lacZ mRNA reaction product in ganglion cells of the retina. Control eyes that received AAV without the promoter and reporter elements and the eyes that received no viral injections and were processed for beta-galactosidase showed no reporter gene expression in any ocular tissue or cell type. CONCLUSIONS: Viral-mediated gene transfer can be successfully accomplished in the optic nerve. Further evaluation is needed to determine whether the level of protein expression at 1 year after injection, which is clearly reduced relative to shorter postinjection time, is sufficient for therapeutic purposes. CLINICAL RELEVANCE: We have previously shown that gene therapy with catalase suppressed experimental optic neuritis at 1 month after injection. Viral-mediated gene transfer may be a powerful technique for the treatment of optic neuropathies, particularly for recurrences of optic neuritis, if long-term expression of transduced protein can be demonstrated in the optic nerve.

Animals↗

PubMed1999

Cancer-associated retinopathy in a patient with advanced epithelial ovarian carcinoma.

BACKGROUND: Paraneoplastic phenomena, such as retinopathy, may herald an unsuspected gynecologic malignancy. CASE: A 75-year-old woman presented to a neuro-ophthalmologist with abrupt onset of unilateral visual loss. A diagnosis of branch retinal artery occlusion was made and she was treated with aspirin. An echocardiogram subsequently revealed atrial dilation and she was placed on coumadin therapy. Her vision worsened and a cancer-associated retinopathy was entertained. A serum cancer-associated retinopathy antibody was detected; subsequent computed tomographies of the abdomen and pelvis revealed findings consistent with a primary ovarian carcinoma. CONCLUSION: Patients with unexplained ophthalmologic symptoms may harbor an underlying gynecologic cancer.

Aged↗

PubMed1999

Murine MHC class II locus control region drives expression of human beta-glucocerebrosidase in antigen presenting cells of transgenic mice.

Gaucher disease is the most prevalent lysosomal storage disorder in humans, resulting from an inherited deficiency of the enzyme glucocerebrosidase. Although the enzyme is ubiquitously expressed, cells of the reticuloendothelial system are particularly affected since they accumulate the undigested glucosylceramide substrate through their role in scavenging and breaking down cell debris. Gaucher disease is an attractive target for somatic gene therapy. To test the ability to express the enzyme in the affected cell types we have generated transgenic mice expressing human glucocerebrosidase under the control of the murine major histocompatibility complex (MHC) class II Ead locus control region (LCR). The four transgenic lines express the human enzyme in a copy number-dependent manner, independent of the integration site of the transgene. Over-expression of the human enzyme in mice did not result in any abnormal phenotype or pathology during the period of observation (> 2 years). The enzyme is expressed in B cells, monocytes, dendritic cells, thymic epithelial cells, and macrophages in various tissues: the peritoneal cavity, bone marrow, spleen, kidney, gastrointestinal tract, Kupffer cells in the liver and alveolar macrophages in lungs. Expression in the brain was limited to perivascular macrophages and was not seen in microglial cells. Therefore, the MHC class II LCR could potentially be of use in somatic gene therapy for type 1 Gaucher disease.

Animals↗

PubMed1999

Sequences flanking the centromere of human chromosome 10 are a complex patchwork of arm-specific sequences, stable duplications and unstable sequences with homologies to telomeric and other centromeric locations.

Little is known about sequence organization close to human centromeres, despite empirical and theoretical data which suggest that it may be unusual. Here we present maps which physically define large sequence duplications flanking the centromeric satellites of human chromosome 10, together with a fluorescence in situ hybridization (FISH) analysis of pericentromeric sequence stability. Our results indicate that the duplications on each chromosome arm are organized into two blocks of approximately 250 and 150 kb separated by approximately 300 kb of non-duplicated DNA. The larger proximal blocks, containing ZNF11A, ZNF33A and ZNF37A (10p11) and ZNF11B, ZNF33B and ZNF37B (10q11), are inverted. However, the smaller distal blocks, containing D10S141A (10p11) and D10S141B (10q11), are not. A primate FISH analysis indicates that these loci were duplicated before the divergence of orang-utans from other Great Apes, that a cytogenetically cryptic pericentric inversion may have been involved in the formation of the flanking duplications and that they have undergone further rearrangement in other primate species. More surprising is the fact that sequences across the entire pericentromeric region appear to have undergone unprecedented levels of duplication, transposition, inversion and either deletion or sequence divergence in all primate species analysed. Extrapolating our data to the whole genome suggests that a minimum of 50 Mb of DNA in centromere-proximal regions is subject to an elevated level of mechanistically diverse sequence rearrangements compared with the bulk of genomic DNA.

Animals↗

PubMed1998

Adeno-associated viral-mediated catalase expression suppresses optic neuritis in experimental allergic encephalomyelitis.

Suppression of oxidative injury by viral-mediated transfer of the human catalase gene was tested in the optic nerves of animals with experimental allergic encephalomyelitis (EAE). EAE is an inflammatory autoimmune disorder of primary central nervous system demyelination that has been frequently used as an animal model for the human disease multiple sclerosis (MS). The optic nerve is a frequent site of involvement common to both EAE and MS. Recombinant adeno-associated virus containing the human gene for catalase was injected over the right optic nerve heads of SJL/J mice that were simultaneously sensitized for EAE. After 1 month, cell-specific catalase activity, evaluated by quantitation of catalase immunogold, was increased approximately 2-fold each in endothelia, oligodendroglia, astrocytes, and axons of the optic nerve. Effects of catalase on the histologic lesions of EAE were measured by computerized analysis of the myelin sheath area (for demyelination), optic disc area (for optic nerve head swelling), extent of the cellular infiltrate, extravasated serum albumin labeled by immunogold (for blood-brain barrier disruption), and in vivo H2O2 reaction product. Relative to control, contralateral optic nerves injected with the recombinant virus without a therapeutic gene, catalase gene inoculation reduced demyelination by 38%, optic nerve head swelling by 29%, cellular infiltration by 34%, disruption of the blood-brain barrier by 64%, and in vivo levels of H2O2 by 61%. Because the efficacy of potential treatments for MS are usually initially tested in the EAE animal model, this study suggests that catalase gene delivery by using viral vectors may be a therapeutic strategy for suppression of MS.

Animals↗

PubMed1998

Effect of hypobaria on ventilatory and CO2 responses to short-term hypoxic exposure in cats.

The effect of hypobaria on the ventilatory response to short-term hypoxia was studied by comparing the respiratory mechanical and inspired CO2 ventilatory responses to hypobaric hypoxia (438 mmHg) with normobaric hypoxia (11.8% FIO2). Fifteen spontaneously breathing, anesthetized cats were divided into three groups of five: time control, normobaric hypoxia and hypobaric hypoxia. Measurements of ventilation, gas exchange, and responses to intermittent CO2 rebreathing were collected over a 4 h period. PaO2 fell to 44.5 +/- 2.7 mmHg, PaCO2 fell to 24.8 +/- 0.9, and pH rose to 7.49 +/- 0.01 in both hypoxic groups. Tidal volume did not change with respect to time or condition, but frequency and ventilation were significantly increased in the hypobaric hypoxic group. The slope of the CO2 response was unchanged over time or by condition. These results suggest that hypobaric hypoxia may alter the pattern of breathing responses to hypoxia but not the CO2-response. If metabolic rate remained constant, these results could be explained by a difference in dead space between hypoxic conditions.

Animals↗

PubMed1998

The effects of interferon-alpha and acyclovir on herpes simplex virus type-1 ribonucleotide reductase.

Herpes simplex virus-type 1 (HSV-1) encodes both the small (UL40) and large (UL39) subunits of the enzyme, ribonucleotide reductase. Treatment of HSV-1-infected cells with interferon-alpha (IFN-alpha) reduced the levels of both enzyme subunits. Reduced steady state levels of the large subunit were demonstrated by immunoblot using polyclonal antibody specific for the viral enzyme. Reduction in the amount of small subunit was shown by a reduction in the electron spin resonance signal derived from the iron-containing tyrosyl free-radical present in this subunit. Treatment of cells with 100 IU/ml of IFN-alpha decreased levels of both subunits resulting in a reduction in enzyme activity as measured by conversion of CDP to dCDP. The decrease in the amount of the large subunit was not due to a reduction in the level of its mRNA. The combination of IFN-alpha and ACV treatment of human cornea stromal cells did not result in a further reduction in amounts of ribonucleotide reductase relative to that detected with IFN-alpha alone. The IFN-alpha-induced reduction in ribonucleotide reductase activity is the likely cause of decreased levels of dGTP which we have previously demonstrated in IFN-alpha-treated, infected cells.

Acyclovir↗