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Biomedical subjects

M Fox

Publications and source records attributed to M Fox.

At least 37 records · Page 2Linked to original sources
PubMed1991

Effects of glycemic control on red cell deformability determined by using the cell transit time analyzer.

There is considerable evidence that blood viscosity is greater than normal in diabetes, and decreased red blood cell deformability has been suggested as the cause. However, viscosity can be influenced by changes in the properties of blood proteins in addition to red cells. Direct interpretation of red cell filtrometry data in terms of deformability has been complicated by the interfering effect of white cells and platelets and clogging of micropores. We have thus used the cell transit time analyzer, a new filtrometric procedure that eliminates these complications and produces an individual red cell micropore transit time profile, to reassess diabetic red cell deformability. Samples from 26 patients with diabetes and an equal number of subjects without diabetes who served as controls were assayed by the cell transit time analyzer at 2 and at 4 cm hydrostatic pressure. Samples from patients with diabetes and controls were sex and age matched for daily runs. At 2 cm H2O, red blood cell transit time for the patients with diabetes was 2.73 +/- 0.05 milliseconds as compared with 2.67 +/- 0.05 milliseconds for controls (p not significant). The ratio of transit time for patients with diabetes to that of controls (Td/Tnd) was 1.03 +/- 0.01 (p less than 0.05, Wilcoxon) at 2 cm H2O and 1.02 +/- 0.01 (p not significant) at 4 cm H2O.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

TAC use and absorption of cocaine in a pediatric emergency department.

The topical anesthetic TAC (tetracaine 0.5%, adrenaline 0.05%, cocaine 11.8%) has been reported to be effective in pain control for local procedures. However, it has the potential for cocaine toxicity by absorption through an open wound. A study was undertaken to assess the systemic absorption of cocaine and its metabolites when TAC is used as a local anesthetic. Fifty-one children, 1 to 14 years of age, were enrolled in the study. Plasma for cocaine and/or its metabolite levels was available from 46 children and obtained 20 to 40 minutes after the topical anesthetic was applied. No plasma sample had detectable parent cocaine levels; however, 26 (56.5%) had cocaine metabolite levels. Ecgonine methylester levels were detected in plasma from six children and ranged from 59 to 985 ng/mL. Benzoylecgonine levels were detected in none of 19 specimens not preserved with sodium fluoride, and in 23 of 27 specimens to which sodium fluoride had been added. Benzoylecgonine levels ranged from 40 to more than 600 ng/mL. No clinical sign of cocaine toxicity was observed in any child.

Administration, Topical↗
PubMed1990

Introduction of the activated N-ras oncogene into human fibroblasts by retroviral vector induces morphological transformation and tumorigenicity.

The introduction of activated N-ras cDNA into normal diploid human skin fibroblast cell cultures using the retroviral vector pZIPneo results in a spectrum of morphologies ranging from near normal to, in rare instances, dense piled-up colonies of morphologically transformed cells. However, none of the clones isolated were transformed as assessed by growth on agar or tumorigenicity in nude mice. Introduction of both c-myc and N-ras oncogene cDNAs into normal skin fibroblasts failed to produce transformation as assessed by growth on agar and tumorigenicity in nude mice, although c-myc infection alone conferred immortality and the resultant doubly infected cell line was immortal. Using the same construct, activated N-ras cDNA was shown to transform immortalized human fibroblasts to tumorigenicity. However, immortalization per se was shown not to guarantee 'co-operation' with an activated N-ras gene to give malignant transformation. Although numerical and structural chromosome aberrations (clonal and non-clonal) were observed in some of the cell strains isolated after retroviral infection, these were not directly associated with viral infection, the presence of the oncogenes or with the morphologically transformed phenotype.

Animals↗
PubMed1990

Methylmethane-sulphonate and X-ray-induced mutations in the Chinese hamster hprt gene: mRNA phenotyping using polymerase chain reactions.

Alterations in the hprt gene of Chinese hamster cells were determined in 71 spontaneous, methylmethane sulphonate (MMS)- and X-ray-induced mutants, using the Southern blot hybridization technique. Among 41 MMS-induced mutants, deletions eliminating the whole gene were observed in 17 cases (41%). Analysis of 20 X-ray-induced mutants revealed the presence of similar deletions in nine of them (45%). No evidence of deletion was found in 10 spontaneous mutants. To investigate the possibility of small deletions, 18 MMS-induced mutants were studied with probes derived from exons 3 and 9 but no evidence of specific deletion of these two exons was found. The polymerase chain reaction (PCR) was used to phenotype hprt transcripts in 48 MMS, X-ray and spontaneous Chinese hamster mutants by amplifying the coding region of their cDNA. Among 22 MMS-induced mutants the message was present in 16 instances; 11 had normal levels while three had much lower levels of transcription. A further two mutants had mRNA of reduced size as revealed by the use of primers for PCR 3' to those routinely used. An analysis of 20 X-ray-induced mutants showed the presence of hprt mRNA in 11 of them with five having low levels of transcription. Among six spontaneous mutants, four were negative for mRNA on standard Northern blots and in one the message was only detected after PCR amplification. Direct DNA sequencing of 10 mutants revealed the presence of base substitutions in five of them while a 7 bp deletion was found in another. No mutations were found in another four mutants, suggesting the presence of mutation outside the coding region.

Animals↗
PubMed1990

Induced reversion of a spontaneous point mutation within the Chinese hamster HPRT gene to the wild-type sequence.

The Chinese hamster hypoxanthine-guanine phosphoribosyltransferase (HPRT)-deficient cell line TG15 produces apparently normal HPRT mRNA by northern analysis and was therefore presumed to contain a point mutation within the coding region. Sequencing cDNA from the TG15 cell line revealed an A to G transition which results in the substitution of the amino acid glycine for aspartic acid at position 135. TG15 cells revert to wild-type HPRT activity upon exposure to monofunctional alkylating agents. A rapid test to assay the site of the TG15 point mutation has been developed, utilizing the polymerase chain reaction and allele-specific oligonucleotide screening. In all revertants studied, the original point mutation has been corrected to the wild-type sequence. The TG15 point mutation lies within a proposed catalytic domain of the HPRT protein in common with other phosphoribosyltransferases.

Animals↗
PubMed1990

Acute effects of insulin-like growth factor I and insulin on glucose metabolism in vivo.

We have compared the actions of insulin-like growth factor (IGF-I) and insulin on glucose metabolism in vivo, using the glucose clamp technique in rats. Both hormones caused dose-dependent inhibition of hepatic glucose production, stimulation of whole body glucose disposal, and an increase in the glucose metabolic rate of specific muscles. Infusion of IGF-I also decreased the plasma concentration of insulin. An an infusion rate of 0.57 nmol.kg-1.min-1, IGF-I led to stimulation of whole body glucose uptake that was similar to the glucose uptake produced by infusion of 0.01 nmol.kg-1.min-1 insulin. The glucose metabolic rate, as measured by 2-deoxy-D-glucose uptake, was comparable in quadriceps femoris, soleus, and diaphragm muscles during the infusion of 0.57 nmol.kg-1.min-1 IGF-I and 0.01 nmol.kg-1.min-1 insulin. However, at these rates of infusion, IGF-I caused only a 38 +/- 6% inhibition of hepatic glucose output compared with 66 +/- 12% inhibition by insulin (P less than 0.05). Thus, under these conditions, muscle is more responsive than liver to IGF-I, which agrees with the complement of IGF-I receptors in the two tissues.

Animals↗
PubMed1990

Model-based analysis of transmural vessel impedance and myocardial circulation dynamics.

The basic structure of a model of the coronary circulation has been developed to explain the relationship between transmural perfusion dynamics and intramyocardial mechanics. The model is in the form of a topologically isomorphic network representation and incorporates experimentally measured time-varying perfusion and intramyocardial pressure sources as driving inputs to the model. The intramyocardial vessels are treated as nonlinear impedance elements possessing regional external pressure-dependent resistance and capacitance. Three circuit branches, perfusing the epicardial, subepicardial, and subendocardial muscle layers, are mathematically modeled and are used to predict time-dependent flow within the left ventricular myocardium. The phasic coronary blood flow characteristics predicted by the model exhibit waveform patterns that correlate qualitatively with those patterns measured experimentally. In addition, the pressure-dependent vascular capacitance induces a sustained (out of phase with arterial inflow) venous systolic flow. The model also exhibits retrograde systolic subendocardial flow and stop-flow pressure, which are dependent on coronary resistive and capacitive properties and on the perfusion pressure decay time constant. Furthermore, the results predict an abrupt decrease in subendocardial flow with perturbation of either arteriolar or capillary bed compliance. The model describes time-dependent intramyocardial properties that have been confusing and controversial in the understanding of coronary circulation dynamics. Several steps are identified that are expected to improve and refine the model significantly.

Animals↗
PubMed1990

Germ cell tumours of testis: prognostic factors and results.

Prognostic features regarding the outcome of 232 patients with testicular germ cell tumours treated from 1980 to 1987 in Sheffield are reviewed. Delay in diagnosis was a constant feature. The majority had a swelling for over 3 months. After 6 months mortality doubled, compared with patients with a shorter history. Initial serum levels of alpha-fetoprotein and beta-human chorionic gondadotropin, particularly if both were elevated over 100, and more so 500 IU/l, indicated a subsequent mortality in non-seminomatous tumours of 24 and 37%, respectively, while only 1.5% died if both values were below 100. The overall survival rate was 97% in seminomas and 78% in non-seminomas; no patients with well or moderately differentiated tumours died. There were no deaths after the 3rd year. Surveillance treatment in stage-I tumours was safe and mortality-free.

Adult↗
PubMed1989

Regional localization of human ecto-5' nucleotidase to chromosome 6q14-q21.

Human and mouse hybrids that contain fragments of human chromosome 6 as translocations were analysed for expression of ecto-5' nucleotidase enzymic activity measured by the conversion of AMP to adenosine and for antigenicity recognized by a monoclonal antibody specific for the human isozyme. Both methods allow a regional assignment of ecto-5'nucleotidase to 6q14-q21.

5'-Nucleotidase↗
PubMed1989

Nucleotide ectoenzyme activities of human and Chinese hamster fibroblasts in tissue culture.

We have previously assigned human ecto-5'-nucleotidase (NT) to chromosome 6 on the basis of conversion of exogenously supplied [14C]AMP to adenosine by whole cells of human and Chinese hamster hybrids carrying chromosome 6. In this paper we demonstrate that the activity on human MRC-5 fibroblasts is typical of previously described and purified ecto-5'-nucleotidases. In contrast to MRC-5 cells, Chinese hamster V79A2 cells weakly express an AMPase activity that is not NT. The cytosolic form of NT in human and hybrid fibroblasts is similar to the ectoenzyme in substrate specificity. Hybrids that lack chromosome 6 express neither the ecto- nor the cytosolic enzyme, suggesting that both forms may be coded by the same gene on chromosome 6. Ecto-ATPase, ecto-ADPase, and ecto-ADP kinase activities are each expressed at similar levels in MRC-5 and V79A2. The ATPase, ADPase and NT activities of MRC-5 cells act sequentially to generate adenosine. A similar cascade acts on V79A2 cells but the lack of NT causes the accumulation of AMP.

5'-Nucleotidase↗
PubMed1989

The in-vitro inhibition of rat alloantigen presentation by immunotoxins--implications for allografting.

The removal of graft interstitial dendritic cells (IDC) prior to transplantation into a recipient has been shown to improve graft survival in a number of experimental studies. We report the in-vitro properties of two immunotoxins (IT) which could be used to deplete graft IDC when administered ex vivo by hypothermic perfusion in an experimental rat transplantation model. Ricin A chain (RAC) IT targeted at either class II major histocompatibility complex (MHC) molecules or leukocyte common antigens (LCA) were prepared. These IT had similar equilibrium constants, binding kinetics and inhibiting activity of cell-free protein synthesis. IT cytotoxicity was assessed by inhibition of alloantigen presentation by targeted low density spleen cells (LDSC) in a one way mixed lymphocyte culture (MLC). When LDSC were hypothermically incubated for 2 h with IT only the anti class II MHC IT inhibited the MLC and the maximum inhibition depended on the cell allotypes. The inhibition was increased to almost 100% when chloroquine was incorporated throughout the culture period.

Animals↗
PubMed1989

N-ras mutation in chemically induced rat brain tumour.

Rat brain tumour was induced by treatment with N-ethyl-nitrosourea. Using Southern blot analysis, restriction fragment length polymorphism of N-ras gene was identified. Comparative studies showed that new restriction site did not occur in the DNA of DMN induced renal and liver tumours. The data suggest that the mutation occurring may be specific to the "target" cell or to the structure of carcinogens.

Animals↗