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Biomedical subjects

G Harris

Publications and source records attributed to G Harris.

At least 127 records · Page 7Linked to original sources
PubMed1988

Interaction of salicylate and corticosteroids in man.

Corticosteroids have been reported to decrease the plasma concentrations of salicylate when salicylates have been administered chronically at high doses. In the present study, two single, oral doses of sodium salicylate, 10 mg kg-1 were administered to six adult subjects with a variety of inflammatory conditions both before and during treatment with daily oral doses of prednisone (12-60 mg). Concomitant prednisone therapy did not increase the whole body clearance of single doses of salicylate in these subjects (0.0275 +/- 0.08 l kg-1 h-1 before prednisone; 0.0247 +/- 0.03 l kg-1 h-1 during prednisone therapy; P greater than 0.05). These results indicate that corticosteroids do not alter the clearance of single doses of salicylate in man.

Adrenal Cortex Hormones↗
PubMed1988

The teenage coeliac: follow up study of 102 patients.

Over a 10 year period a total of 102 teenage patients with coeliac disease were assessed on transfer from paediatric hospitals to an adult clinic. Fifty seven patients said they were on a strict gluten free diet; 36 were semistrict, and nine admitted to eating a normal diet. Jejunal mucosal abnormalities, however, suggested that many patients on the 'strict' diet were actually consuming gluten. All patients were well with biochemical parameters within the normal range. Height percentiles were not significantly different from the normal population but patients, as a group, were significantly lighter.

Adolescent↗
PubMed1988

Increased sensitivity of lymphocytes from patients with systemic autoimmune diseases to DNA alkylation by the methylating carcinogen N-methyl-N-nitrosourea.

Lymphocytes from patients with various diseases associated with autoimmunity showed both impaired capacity to repair O6-methylguanine (a powerful, promutagenic, directly miscoding base lesion) and increased sensitivity to the cytocidal effects of cellular methylation by N-methyl-N-nitrosourea (MNU) compared with normal controls and patients with other disorders. Defective repair of O6-methylguanine was significantly associated with arthritis and myositis in the group with systemic lupus erythematosus (SLE), and increased sensitivity to the toxic action of MNU was associated with the presence of immune complexes and the administration of steroids to patients with Behçet's syndrome. The results indicate that lymphocytes from patients with the autoimmune diseases studied are more susceptible to DNA damage with possible relevance to aetiopathogenesis.

Adult↗
PubMed1988

Deficient repair of O6-methylguanine in lymphocytes from rheumatoid arthritis families may be an acquired defect.

Deficient repair of the premutagenic DNA lesion O6-methylguanine (O6-MeGua) has been reported in lymphocytes from patients with autoimmune diseases. This was confirmed in the present study of probands with rheumatoid arthritis (RA) and their families. We also noted a significant deficiency in 9/19 spouses (P less than 0.05) and a statistically non-significant deficiency of repair of O6-MeGua in 14/42 first and second degree relatives in comparison with healthy and non-autoimmune disease controls, respectively. A significant correlation of the repair status of O6-MeGua in DNA between individual probands with RA and respective spouses (P less than 0.01) and probands and respective family members (P less than 0.001) supported the idea that an environmental, transmissible agent could influence the expression of the protein, O6-methylguanine-DNA-transferase (O6-MT), involved in the repair of O6-MeGua. The present results, however, cannot entirely exclude an additional hereditary influence.

Adolescent↗
PubMed1987

2'-Deoxy-2'-halonucleotides as alternate substrates and mechanism-based inactivators of Lactobacillus leichmannii ribonucleotide reductase.

The interaction of the ribonucleoside-triphosphate reductase of Lactobacillus leichmannii with various 2'-halogenated ribo- and arabinonucleoside triphosphates has been investigated. All analogues examined acted as mechanism-based inactivators of the enzyme, producing base, triphosphate, and halide. In all cases, the inactive enzyme had developed the distinctive chromophore at 320 nm that is characteristic of enzyme inactivated by 2-methylene-3(2H)-furanone. The striking similarities between these results and those previously reported for the inactivation of this enzyme by 2'-chloro-2'-deoxyuridine triphosphate suggest a common reaction path for all 2'-halonucleotides. In the pyrimidine series, it was found that 2'-fluoro- and 2'-chloronucleotides partitioned between inactivation and formation of the normal reduction product 2'-deoxynucleotide. Normal reduction predominated with 2'-fluoronucleotides, whereas it was a minor pathway for 2'-chloro-2'-deoxyuridine triphosphate. With 2'-chloro-2'-deoxyuridine triphosphate, the relative partitioning between the two modes was pH dependent: the amount of 2'-deoxyuridine triphosphate formed increased 2.8-fold upon changing from pH 6.1 to pH 8.3. The ability of 2'-arabinohalonucleotides to inactivate ribonucleotide reductase and the variation of partitioning of the pyrimidine analogues with leaving group and reaction pH are consistent with our radical cation hypothesis and support the proposal that the difference between normal catalysis and inactivation is related to the protonation state of the reductase.

Deoxyribonucleotides↗
PubMed1987

Induction of thymomas by N-methyl-N-nitrosourea in AKR mice: interaction between the chemical carcinogen and endogenous murine leukaemia viruses.

AKR mice develop thymomas spontaneously when greater than 6 months old but when young AKR mice are treated with N-methyl-N-nitrosourea (MNU) they develop thymomas at 3-6 months of age. In this study the potential role of oncogene activation in the development of both the spontaneous and MNU-induced thymomas in AKR mice has been examined by DNA transfection into NIH3T3 mouse fibroblasts and by Southern analysis of tumour DNA. The results show that a high proportion of MNU-induced thymomas contain activated cellular rasK while no activated cellular ras genes were detected in spontaneous thymomas. Southern analysis of tumour DNA revealed that 2/30 spontaneous tumours and 2/52 MNU-induced tumours contained alterations in the c-myc gene while 5/29 spontaneous tumours and 6/56 MNU-induced tumours contained alterations in the Pim-1 gene. A more detailed analysis of the Pim-1 gene demonstrated that the alterations observed in most MNU-induced and spontaneous tumours resulted from proviral integration at the 3' end of this gene. Our analyses also demonstrated that the majority of MNU-induced tumours, including those containing rearrangements in the Pim-1 gene, lacked the somatically acquired recombinant MCF proviruses that are present in most spontaneous AKR lymphomas. These results provide evidence that the mechanisms of development of MNU-induced and spontaneous tumours in AKR mice are distinct and the development of thymomas that contain proviral integrations at the Pim-1 locus in the MNU-treated AKR mice involve cooperation between the chemical carcinogen and endogenous murine leukaemia viruses.

Animals↗
PubMed1987

DNA quaternary structure in the radiation sensitivity of human lymphocytes--a proposed role of copper.

On challenging with 2M NaCl, the nuclei of human lymphocytes yield an aggregate of DNA-protein material. The density of the material is less when isolated from irradiated cells than when isolated from unirradiated cells. The density of this material, designated histone-free-DNA (HF-DNA), from irradiated cells returns to that from unirradiated cells if the irradiated cells are allowed time at 37 degrees C in nutrient conditions. Lymphocyte HF-DNA from patients who have exhibited hypersensitivity to radiotherapy exhibit slower repair characteristics than lymphocyte HF-DNA from the average normal subjects. Neutrons are more effective than X-rays in producing density changes. Misonidazole and the ADPRT inhibitor 3-AAB substantially inhibit return to unirradiated densities. The oer for the initial effect is between 2 and 3. These properties of this DNA material from human lymphocytes suggest that alterations in the configuration of such material by the loss and re-establishment of relatively weak cellular bonds are closely related to the well-known changes observed in classical cell survival experiments. Where the proliferation of human lymphocytes has been observed by concanavalin A stimulation, oer, RBE and chemical modification has been of the same order as the measured density changes. Additionally, we have found that the density of HF-DNA is heavily dependent upon Cu content. This has led us to propose that cell killing or malfunction at the nuclear level caused by ionizing radiation is caused by the conversion CuII----CuI and also by specific .OH attack on DNA or proteins at a Cu site.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Survival↗
PubMed1986

The mechanism of Lactobacillus leichmannii ribonucleotide reductase. Evidence for 3' carbon-hydrogen bond cleavage and a unique role for coenzyme B12.

Reduction of [3'-3H, U-14C]UTP with ribonucleotide reductase showed isotope effects of 1.6, 1.8, and 1.8 at pH 6.1, 7.3, and 8.3, respectively. Similar studies with [3'-3H, U-14C]ATP gave effects of 2.1, 2.1, 1.7, and 1.9 at pH 5.5, 6.1, 7.3, and 8.3, respectively. During the course of the isotope effect determinations the samples were analyzed for the production of 3H2O. Reduction of [3'-3H]UTP at pH 6.1, 7.3, and 8.3 resulted in 0.08, 0.15, and 0.24% of the total 3H being volatilized at 50% reaction. Reduction of [3'-3H]ATP gave no detectable 3H2O at pH 6.1 or 7.3 and a maximum of 0.02% at pH 8.3. The isotope effects in conjunction with 3H2O production indicate that ribonucleotide reductase catalyzes cleavage of the 3' carbon-hydrogen bond of NTPs during the reduction to dNTPs. The role of the cofactor, adenosylcobalamin (AdoCbl), was also investigated. Incubation of [3'-3H]NTP with prereduced ribonucleotide reductase in the absence of reductant (one-turnover conditions) followed by isolation and analysis of AdoCbl for radioactivity indicated no 3H transfer from substrate to cofactor and no 3H2O production. Similar results were obtained in the presence of DTT (multiple turnover conditions). The role of AdoCbl was further investigated by examination of its potential to mediate hydrogen transfer between two substrates. Incubation of [3'-3H]UTP and unlabeled ATP with ribonucleotide reductase and isolation of the products produced indicated no 3H in dATP. These results allow us to postulate a unique role for AdoCbl in the ribonucleotide reductase reaction, that of a radical chain initiator rather than an intermediary hydrogen transfer agent.

Adenosine Triphosphate↗
PubMed1986

Repair of chemical carcinogen-induced damage in DNA of human lymphocytes and lymphoid cell lines--studies of the kinetics of removal of O6-methylguanine and 3-methyladenine.

The removal of O6-methylguanine by human lymphoid cells corresponded, with certain assumptions, to a second-order chemical reaction in any given cell. There was a spectrum of proficiency in this respect for a considerable number of cells originating from different individuals and it was found that patients with diseases associated with autoimmunity tended to fall into the less proficient groups. E-B virus-induced lymphoid cell lines, derived from proficient, but not relatively deficient, peripheral blood lymphocytes, always (in 9/9 cases) reflected the level of proficiency of the donor lymphocytes with respect to removal of O6-methylguanine. Thus while proficient lymphocytes always produced proficient cell lines, deficient lymphocytes, in 3/8 cases, gave rise to more proficient cell lines. No evidence was found that groups of individuals exist who lack ability to remove 3-methyladenine from DNA, either from their blood lymphocytes or derived lymphoid cell lines.

Adenine↗
PubMed1986

Sensitivity to X-irradiation of peripheral blood lymphocytes from ageing donors.

The proliferation of human blood lymphocytes from ageing donors, responding to concanavalin A, showed greater sensitivity to inhibition by X-rays than similar cells from younger donors. This increased sensitivity was associated with deficiency in repair of X-ray-induced damage to nuclear material, as measured by density in sucrose gradients, and with increased incidence of chromosomal damage following exposure of freshly isolated lymphocytes. There was also an increased frequency of spontaneous chromosomal aberrations in ageing subjects whose lymphocytes were deficient in repair of DNA damage.

Aged↗
PubMed1986

Water environment microwave thawing.

A rapid, controlled microwave oven thawing technic for fresh frozen plasma (FFP) that minimizes flocculent formation while maintaining excellent coagulation factor, total protein, and albumin levels is presented. This method, using an unmodified microwave oven and a tap-water environment, decreases thawing time from 37.5 minutes for the standard 37 degrees C water bath to approximately 11 minutes for either one or two units of FFP.

Blood Protein Electrophoresis↗
PubMed1986

The context and content of community hospital admissions.

Hospital admissions from a general practice were studied for one year. One-third of all admissions were found to be to a community hospital. Those admitted were mainly elderly people. The majority of patients stayed in the community hospital only a short time and 69% of patients returned home on discharge. Social, nursing and medical factors determined admission and discharge. Social factors were found to be increasingly important as the age of patients increases while medical factors become less important.

Adolescent↗
PubMed1985

Histochemical assessment of cytochrome oxidase activity for monitoring ischemic muscle injury.

Electromyographic detection of increased neuromuscular conduction latency that follows electrostimulation of spinal nerves has been used widely as a clinical tool for detection of ischemic muscle injury. We hypothesized that a biochemical marker for stagnant hypoxia provides more direct evidence for evaluating severity and monitoring resolution of ischemic muscle injury than the EMG. To detect intracellular changes in oxygen use during experimental ischemia, ultrathin sections of rat gastrocnemius muscle were treated with reducing agent, 3,3'-diaminobenzidine (DAB), a histochemical marker for intramitochondrial cytochrome oxidase activity. The observed decrease in mitochondrial uptake of DAB suggested that a decrease in cytochrome oxidase activity was associated with experimental ischemia. Neuromuscular conduction latency in rat gastrocnemius muscle was also quantitated after electrostimulation of the sciatic nerve. Ligation of the femoral artery produced ischemic tissue injury, during which recordings of the EMG showed that conduction latency increased [from a mean +/- SEM control value of 3.09 +/- 0.13 to 3.92 +/- 0.22 ms (N = 11, P less than 0.001).] The changes in both histochemically detectable cytochrome oxidase activity and neuromuscular conduction latency were reversed by reperfusion. Response of the rat tissue to arterial occlusion was thereby shown to be a physiologic model for skeletal muscle response to ischemia. In addition, histochemical detection of cytochrome oxidase activity was shown to be a sensitive intracellular marker for decreased oxygen use during ischemic muscle injury.

Animals↗
PubMed1985

Radiosensitivity of peripheral blood lymphocytes in autoimmune disease.

The proliferation of peripheral blood lymphocytes, cultured with Con A, can be inhibited by ionizing radiation. Lymphocytes from patients with conditions associated with autoimmunity, such as rheumatoid arthritis, systemic lupus erythematosus and polymyositis, are more radiosensitive than those from healthy volunteers or patients with conditions not associated with autoimmunity. The nuclear material isolated from the lymphocytes of patients with autoimmune diseases is, on average, lighter in density than the nuclear material from most healthy controls. This difference in density is not related to increased sensitivity to ionizing radiation but the degree of post-irradiation change in density (lightening) is proportional to the initial density, i.e. more dense nuclear material always shows a greater upward shift after radiation. The recovery of preirradiation density of nuclear material, 1 h after radiation exposure, taken as an indication of DNA repair, correlates with the radiosensitivity of lymphocyte proliferation (Con A response); failure to return to pre-irradiation density being associated with increased sensitivity of proliferative response. These results require extension but, taken with previously reported studies of the effects of DNA methylating agents, support the idea that DNA damage and its defective repair could be important in the aetio-pathogenesis of autoimmune disease.

Adult↗