PubMed Health⌕ Search

Biomedical subjects

M Fox

Publications and source records attributed to M Fox.

At least 145 records · Page 8Linked to original sources

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↗

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↗

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↗

Ambulatory practice variation in Maryland: implications for Medicaid cost management.

Simulation modeling with data from the Maryland Medicaid Management Information System has provided an opportunity to examine policy options and assess their likely impact on savings before program decisions were made. Analysis of a large sample of the Maryland Aid to Families with Dependent Children (AFDC) Medicaid subpopulation confirms that a significant difference in utilization and cost to Medicaid exists between usual sources of care for AFDC clients even after controlling for patient demographics and case-mix differences. Findings indicate that savings from reduced use of hospital outpatient departments may offset increases of as much as 40-50 percent in physician fees under certain assumptions.

Adolescent↗

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↗

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↗

Pseudomembranous trigonitis of the bladder: hormonal aetiology.

Fourteen formalin fixed and paraffin wax embedded biopsy specimens from 10 women (age range 34-68) presenting with pseudomembranous trigonitis were studied using a combination of anti-oestrogen receptor monoclonal antibodies in an avidin-biotin immunoperoxidase technique. All epithelial areas showing vaginal metaplasia exhibited staining confined to the nucleus in the basal and parabasal layers of the squamous epithelium while no staining was encountered in adjacent trigonal transitional epithelium included in nine of the biopsy specimens. The selective expression of nuclear oestrogen receptor in trigonal epithelium affected by vaginal metaplasia in a distribution similar to that reported in vaginal epithelium by other workers lends further support to oestrogen mediated aetiology in this condition and is consistent with an embryological derivation of the trigone, distinct from that of the rest of the bladder.

Adult↗

Fax technology: elegant solution for lab.

A shot in the arm from fax technology has invigorated a cumbersome manual laboratory system at Baptist Medical Center in Kansas City, Mo. Using a hot, proliferating technology, BMC developed a system for lab ordering/results reporting that interfaces to the LIS mainframe, links to stations on and offsite, and is less costly than other alternatives.

Clinical Laboratory Information Systems↗

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↗

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↗

Validity of self-estimated and weighed dietary data for assessment of military rations.

Validity of food intake values, self-estimated by subjects and weighed by researchers, was evaluated during the assessment of a new military ration. As an addition to food intake measured by the two methods, a third set of intake values was generated by combining food intakes from the self-estimated and weighted data. This combined method is proposed as another reference for assessing validity. The new ration, Meal-Ready-to-Eat (MRE), was the sole source of food for an experimental group of 27 soldiers engaged in a 34-day field exercise. A control group of 30 soldiers ate a freshly prepared (A ration) breakfast and dinner and an MRE lunch. Agreement of mean nutrient intake values from self-estimated and weighed data was high among both experimental and control groups (average coefficients of correlation for 16 nutrients, 0.948 and 0.884, respectively). Paired t-tests yielded no significant differences between self-estimated and weighed means for nutrient intake but were significantly different from the means obtained by the combined method (p less than .0001). Mean nutrient intakes determined by both the self-estimated and weighed methods approached 90% of the intakes found by the combined method.

Adult↗

TPA enhancement of the recovery of methotrexate and N-phosphonacetyl L-aspartate resistant mouse 3T6 cell clones is associated with transient alterations of cell cycle progression.

The effects of methotrexate (MTX) and N-phosphonacetyl L-aspartate (PALA) with and without 12-O-tetradecanoylphorbol-13-acetate (TPA) have been tested on the cell-cycle traverse of mouse 3T6 and Chinese hamster V79 cell lines. MTX, whether administered with or without TPA, had very little effect on the cell cycle of the V79 Chinese hamster cell line. However, low MTX concentrations produced a significant G1 accumulation in the mouse 3T6 cell line after 24 hr, and this was accentuated by TPA treatment. These findings parallel previous observations that TPA enhances the recovery of MTX- and PALA-resistant mouse 3T6 cell clones but has little or no effect on drug-resistant colony recovery in the V79 Chinese hamster cell line. The possibility that the increase in accumulation of cells in G1 might permit the rescue of an increased proportion of cells due to the release of purines and pyrimidines from dying cells is discussed. Such rescue should occur irrespective of whether or not the cell line has the ability to amplify its target genes.

Animals↗

Phenotypic resistance to methotrexate and N-phosphonacetyl L-aspartate is induced by treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA).

Three different 3T6 mouse fibroblast cell clones with intrinsically different sensitivities to methotrexate (MTX) have been isolated from an originally heterogeneous population. When these 3 different clones were exposed to MTX in the presence of the tumour promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) the degree of enhancement of recovery of methotrexate resistant (MTXR) colonies was greatest in the most sensitive clone. MTXR colonies isolated and cultured in the presence and absence of MTX and TPA were analysed for dihydrofolic acid reductase (dhfr) levels by flow cytometry after binding of fluorescent methotrexate. None of the 58 clones showed major changes in dhfr levels. Dot-blot analysis of 12 clones indicated no increases in dhfr gene copy number or mRNA levels consistent with gene amplification. Southern analysis of 6 further clones indicated that only 1 clone isolated by multi-step selection had amplified dhfr sequences. TPA-enhanced mouse 3T6 N-phosphonacetyl-L-aspartate (PALA)-resistant colony recovery and mouse 3T3 MTXR colony recovery were also shown, by dot-blot analysis, not to be due to gene amplification. The data indicate that TPA can have a profound effect on drug-resistant colony recovery by mechanisms other than induction of gene amplification.

Animals↗