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Biomedical subjects

N Atkinson

Publications and source records attributed to N Atkinson.

34 records · Page 2Linked to original sources
PubMed1988

Prospective randomized trial of high-dose cisplatin and fluorouracil infusion with or without sodium diethyldithiocarbamate in recurrent and/or metastatic squamous cell carcinoma of the head and neck.

Previous studies have indicated that sodium diethyldithiocarbamate (DDTC) can reduce cisplatin's (CP) toxic effects without altering the antitumor activity. DDTC has also been shown to have immunostimulative properties. Sixty patients with objectively measurable recurrent and/or metastatic squamous cell carcinoma (SCC) of the head and neck were randomized to receive either (A) CP at 120 mg/m2 over one hour on day 1, plus fluorouracil (5-FU) at 1,000 mg/m2 over 24 hours as a continuous infusion on days 1 through 5, or (B) CP/5-FU as in A, plus DDTC at 600 mg/m2 over 30 minutes administered intravenously (IV) exactly 30 minutes after CP infusion. Group B also received DDTC at 200 mg/m2 administered IV over 30 minutes on days 8 and 15. Each cycle was repeated at 3-week intervals. Objective responses were achieved in 41% of the CP/5-FU group and in 29% of the CP/5-FU with DDTC group (P = .26). Median survival was 9 months in group A and 10 months in group B. CP-related toxicity between the groups was equivalent with respect to nausea and vomiting, renal impairment, neurotoxicity, ototoxicity, and hematologic toxicity. The pharmacokinetics of reactive platinum species in plasma ultrafiltrate and urine samples obtained from both groups were comparable. The immune status of 48 patients was evaluated before and after completion of therapy. There were no significant differences in mean pretreatment and posttreatment values within or between groups A or B, except for absolute pretreatment OKT4 values (P = .02). We conclude that (1) the present dose and infusion schedule of DDTC did not significantly reduce CP-mediated toxic effects, (2) DDTC did not alter the disposition of ultrafilterable platinum species, (3) DDTC did not affect immune responses, and (4) the addition of DDTC improved neither the clinical response nor the survival of patients with recurrent SCC of the head and neck.

Adult↗
PubMed1984

Blood and liver acetaldehyde concentrations during ethanol oxidation in C57 and DBA mice.

Hepatic and blood acetaldehyde concentrations during ethanol oxidation were determined in C57 and DBA mice. Liver acetaldehyde was determined with the perchloric acid-thiourea method (no artefactual acetaldehyde formation). Levels ranging from 5 to 118 nmole/g were observed. At ethanol concentrations below 50-60 mumole/g, liver acetaldehyde concentrations were higher in DBA compared with C57 mice. A positive correlation was found between the ethanol and acetaldehyde concentration, when ethanol concentration was below 25 (DBA) or 70 mumole/g (C57). At higher ethanol concentrations the correlations tended to become negative. Artefactual acetaldehyde formation during the analytical procedures was obtained with the use of hemolysis, with or without thiourea, and semicarbazide methods for blood acetaldehyde determination. The magnitude of the artefactually formed acetaldehyde was of such order that no conclusions regarding the existence of true in vivo blood acetaldehyde concentrations could be drawn. Earlier reported mice blood acetaldehyde concentrations are suggested to be re-evaluated.

Acetaldehyde↗
PubMed1982

Increase in hepatic microsomal ethanol oxidation by a single dose of ethanol.

A single injection of ethanol was shown to produce a relatively rapid increase in the in vitro activity of aniline hydroxylase and in microsomal ethanol oxidation. Stimulation of the microsomal ethanol oxidating system (MEOS) was dependent on the ethanol dose and time after dosing. Hepatic MEOS activities were significantly increased 2, 3 and 4 hr after a single 4.0 g/kg i.p. dose of ethanol and 4 hr after administration of 2.0 and 3.25 g/kg doses. Renal MEOS activity was also significantly increased 4 hr after a 4.0 g/kg dose of ethanol. Hepatic MEOS and aniline hydroxylase activities per gram of liver were significantly increased 2 hr after a 4.0 g/kg dose of ethanol, whereas microsomal cytochromes P-450 and b5, NADPH cytochrome c reductase, protein and NADPH-stimulated and ethanol/NADPH-stimulated lipid peroxidation were unchanged. Cycloheximide pretreatment did not block ethanol-induced stimulation of aniline hydroxylase or MEOS activity. Finally, an acute injection of ethanol (4.0 g/kg) produced significantly higher MEOS activities per gram of liver (121% of control) in mice chronically ingesting ethanol than in mice treated with saline. This investigation shows that MEOS activity can respond rapidly to a dose of ethanol and that synthesis of new protein is not responsible for this stimulation of activity.

Aniline Hydroxylase↗
PubMed1981

The effects of chronic ethanol ingestion on ethanol binding to hepatic cytochrome P-450 and on certain hepatic and renal parameters in the "long sleep" and "short sleep" mouse.

Male mice selected for genetic differences in ethanol-induced sleep time, thereby designated long sleep (LS) an short sleep (SS), were treated with the Lieber-DeCarli liquid diet for 25 days. This chronic ethanol treatment produced an increase in liver/body weight and kidney/body weight in SS mice only. In addition, chronic ethanol treatment produced significant increases in both LS and SS treated mice in in vivo ethanol elimination, hepatic cytochromes P-450 and B5, NADPH cytochrome c reductase and hepatic and renal 7-ethoxycoumarin O-de-ethylase activity. Genotypic differences were observed in the magnitude of response of microsomal ethanol oxidation per mg of microsomal protein (SS greater than LS). Further, control LS and SS mice possessed substantially different activity of renal 7-ethoxycoumarin O-de-ethylase. Both lines exhibited similar induced renal 7-ethoxycoumarin O-de-ethylase activity after chronic ethanol ingestion. Ethanol binding spectra produced when ethanol was added to hepatic microsomes were examined using double reciprocal plots. Chronic ethanol ingestion produced genotypically related (LS greater than SS) increases in the absorbance change maximum per mg of microsomal protein. No significant changes in the spectral dissociation constant or absorbance change maximum per nM cytochrome P-450 were observed following ethanol treatment.

Alcoholism↗
PubMed1980

Genetically mediated responses of microsomal ethanol oxidation in mice.

Long-sleep (LS) and Short-sleep (SS) male mice were treated chronically with alcohol for 30 days. Ethanol treated mice were withdrawn from alcohol diet at 8, 12, 16, 20, 24 and 30 days of treatment for the assessment of metabolic tolerance and numerous parameters associated with the microsomal cytochrome P-450 complex. Up to 20 days of ethanol treatment, LS and SS mice displayed nearly the same enhancement of in vivo ethanol elimination rates. AT 24 and 30 days of ethanol treatment, LS mice were found to have significantly greater ethanol elimination rates than SS mice chronically treated with alcohol. The induction of microsomal cytochrome P-450 content and microsomal ethanol oxidation paralleled the acquisition of metabolic tolerance with LS mice displaying significantly greater values of both microsomal parameters at 24 and 30 days of treatment. Aniline hydroxylase was maximally induced (2.5 fold) in both LS and SS mice by 16 days of treatment. Chronic ethanol treatment resulted in a significant induction of ethylmorphine and benzphetamine N-demethylase activity in both LS and SS mice with the SS selected line showing a greater (P < .05) maximal induction. These data are suggestive that the induction of MEOS may have some significance in the acquisition of metabolic tolerance to ethanol and that there may be a genetic predisposition for these adaptive responses.

Alcohol Drinking↗
PubMed1980

The role of liver cytosolic aldehyde dehydrogenase in ethanol metabolism in DBA and C57Bl mice.

Cytosolic aldehyde dehydrogenase (AlDH) activity was increased in DBA and C57Bl mice following phenobarbital (Pb) treatment. The kinetic constants for the control and induced enzymes were similar in both inbred strains. The DBA mice showed enhanced rates of ethanol and acetaldehyde metabolism after Pb treatment, whereas the C57Bl mice did not. It was concluded that the cytosolic enzyme is more important for acetaldehyde metabolism in the DBA than in the C57Bl mice.

Acetaldehyde↗
PubMed1976

Streptomycin and temperature sensitivity of colicin-like activity in Salmonella cultures.

Salmonellin production on agar was reduced by adding streptomycin or raising the incubation temperature to 44 degrees. Production of group 3b salcol was increased by incubation at 44 degrees and, for one producer only, by adding streptomycin. Production of the diffusible, nontransferable group 4 salcol and also of diffusible colicin V was reduced at 44 degrees. Group 1 salcol production was unaffected by raised temperature or streptomycin. Group 2 salcol production also was unaffected, except in salm+ transcipients of Arizona So116 where it was reduced along with salmonellin production by incubation at 44 degrees or addition of streptomycin.

Bacteriocins↗
PubMedDate not supplied

Augmentation of in vitro lymphocyte blastogenesis and cytotoxicity responses by tumor cells modified with dodecanoyl cytochrome C.

In a model testing the immune responsiveness of allogeneic lymphocytes against the human cervical cancer cell line SW756, tumor cells coupled to dodecanoyl cytochrome C (D-cyt C) demonstrated augmented immunogenicity. The coupling was noncovalent; the D-cyt C spontaneously associated with the SW756 cells during mixing. Augmented immunogenicity was shown in both in vitro blastogenesis and cytotoxicity assays. The extent of cell-associated D-cyt C, which influenced the in vitro responsiveness, was easily controlled. Increased lipoprotein concentrations and increased lipid substitution of the cyt Cs led to greater cell uptake. Under the maximum conditions, 60-80 micrograms D-cyt C were bound/10(7) SW756 cells. In the blastogenesis assay, augmented immunogenicity was observed on days 3 and 4 after cocultivation of the allogeneic lymphocytes with the modified SW756 cells. When cells modified by the optimal D-cyt C preparations (as determined in the blastogenesis assay) were tested in the cytotoxicity assay, augmented responses were observed across a range of lymphocyte:tumor cell ratios. Our results demonstrate that the modification of SW756 cells with D-cyt C can augment the immune responses detected in in vitro assays.

Adhesiveness↗
PubMedDate not supplied

Prognostic factors in bronchoalveolar lavage in 77 patients with bone marrow transplants.

OBJECTIVE: To study the prognostic implications of the following factors in bronchoalveolar lavage (BAL) specimens in bone marrow transplant (BMT) patients: number of lymphocytes per high-power field (HPF), presence of hemosiderin-laden macrophages (HLMs), presence of infections and presence of reactive epithelial cellular changes in bronchial and alveolar cells. STUDY DESIGN: A retrospective study of 77 bone marrow transplant patients who required BAL. Each specimen was studied for the number of lymphocytes per HPF, presence of HLMs, presence of infection and presence of reactive epithelial cells. RESULTS: Patients who had < or = 5 lymphocytes per HPF had a much higher death rate than did patients who had > 5 lymphocytes per HPF (P < .001). Eighty-nine percent of patients who had < or = 5 lymphocytes per HPF died within 30 days of undergoing BAL (P < .001). Patients without HLMs had a better prognosis than did patients with HLMs (P < .005). Thirty-six documented viral or fungal infections occurred in 33 patients. Patients with infections had a greater chance of dying than did those who were infection free (P < .05). Multiple logistic regression analysis showed that the previous three factors are statistically significant. Reactive epithelial cellular changes were seen primarily in patients with autologous BMT (11 of 14 cases) and in those with hematologic malignancies, but they had no statistical significance prognostically. CONCLUSION: The following factors in BAL have a good prognostic value: number of lymphocytes > 5 per HPF, absence of HLMs and absence of infections. Reactive epithelial cellular changes have no prognostic value.

Bone Marrow Transplantation↗