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Biomedical subjects

J D Bell

Publications and source records attributed to J D Bell.

At least 145 records · Page 8Linked to original sources
PubMed1988

Turbulence and change--the veterinary profession in a competitive environment.

This paper examines the views of members of the veterinary profession towards the change in orientation of professional practice that is occurring. It contrasts the values of veterinarians with those of doctors, dentists, lawyers and accountants. Particular attention is given to the areas of business efficiency, competition and advertising. Data was derived from self-completion questionnaires containing 40 Likert scales which were mailed to 300 members of each of the five professions.

Journal Article↗
PubMed1987

1H NMR studies of human blood plasma. Assignment of resonances for lipoproteins.

Single-pulse and Hahn spin-echo 500 MHz 1H NMR spectra of human blood plasma and isolated chylomicrons, VLDL, LDL and HDL are reported. The comparison has enabled specific assignments to be made for the resonances of individual lipoproteins in the CH2 and CH3 (fatty acid), and NMe+3 (phospholipid choline head group) regions of the spectra of plasma (0.8-1.3 and approximately 3.25 ppm, respectively). Fasting, and freeze-thawing of plasma samples led to marked changes in the intensities and linewidths of lipid resonances. Analysis of lipid resonances in the spectra of plasma in terms of individual lipoproteins may shed new light on many conditions of clinical and biochemical interest.

Humans↗
PubMed1987

Assignment of resonances for 'acute-phase' glycoproteins in high resolution proton NMR spectra of human blood plasma.

Broad resonances at 2.04 and 2.08 ppm in 500 MHz Hahn spin-echo 1H NMR spectra of human blood plasma are assigned to the N-acetyl groups of mobile carbohydrate side-chains (largely N-acetylglucosamine and N-acetylneuraminic acid) of glycoproteins such as alpha 1-acid glycoprotein. Their intensities in spin-echo spectra correlate with clinical conditions in which an elevation of the level of 'acute-phase' glycoproteins is expected, and so may be of value in the study of certain diseases.

Acute-Phase Proteins↗
PubMed1987

Coordination chemistry in biological media: reactions of antitumor Pt(II) and Au(III) complexes with cell culture media.

Reactions of cis-PtCl2(NH3)2 (1), Pt(1,2-diaminoethane)Cl2 (2), PtCl4(2-) (3), and AuCl4- (4) with intact cell culture media have been studied by spin-echo 500 MHz proton NMR spectroscopy. This has allowed us to observe reactions of components of the media at submillimolar concentrations. Upon the addition of 400 microM 1, 2, or 3 to the media, the S-methyl peak of methionine decreases in intensity and in each case a new peak appears which we have tentatively assigned to the S-CH3 of Pt(N,S-L-Met)2. In the spectra of the media with 2, an additional peak appears, assignable to the S-CH3 of Pt(1,2-diaminoethane)(N,S-L-Met). Upon the addition of Au(III) to the media, the S-CH3 peak of methionine also decreases in intensity and new peaks appear in the 2.6 to 2.8 ppm region, including a peak identified as the S(O)-CH3 peak of methionine sulfoxide. The other peaks are assignable to Au(I)-S(Met) species. Practical methods of following the reactions of metal complexes in cell culture media are becoming of wider significance with the increasing use of cell cultures for drug screening instead of animal tests.

Antineoplastic Agents↗
PubMed1987

High resolution proton nuclear magnetic resonance studies of human cerebrospinal fluid.

One- and two-dimensional (correlated shift spectroscopy) high resolution proton n.m.r. spectra of human cerebrospinal fluid (CSF) are reported. The merits of water suppression by freeze drying or irradiation, and spectral simplification by spin-echo methods, are discussed. Well-resolved resonances for a range of low molecular weight metabolites such as lactate, 3-D-hydroxybutyrate, alanine, acetate, citrate, glucose, valine and formate were observed. Resonances for glutamine were observed only from freeze dried samples. Concentrations determined by n.m.r. were in reasonable agreement with those from conventional methods. The n.m.r. spectra of CSF were related to the clinical conditions of the subjects. No resonances for citrate were present in spectra of CSF from subjects (three infants) with bacterial meningitis; high lactate and lowered glucose levels were observed. Strong resonances for glucose and glycine were observed for mildly diabetic subjects. Both the aromatic and the aliphatic regions of the CSF spectra from subjects suffering from liver failure contained distinctive features characteristic for hepatic coma: Intense resonances for lactate, alanine, valine, methionine, tyrosine, phenylalanine and histidine. In some cases guanine was also present, which does not appear to have been reported previously. The two-dimensional spectrum suggested the presence of abnormally high levels of a number of endogenous metabolites. Such assignments were not possible using one-dimensional spectra alone because of signal overlap.

Acetates↗
PubMed1987

Multiple effects of phorbol esters on hormone-sensitive adenylate cyclase activity in S49 lymphoma cells.

In S49 lymphoma cells, 12-O-tetradecanoyl phorbol-13-acetate (TPA) enhances adenylate cyclase activity and doubles cAMP accumulation in response to beta-adrenergic stimulation at 37 degrees C, putatively via the action of protein kinase C. At 27 degrees C, TPA has the opposite effect, inhibiting cAMP production in response to isoproterenol by approximately 25%. TPA also inhibits the response to prostaglandin E1 (PGE1), another stimulant of hormone-sensitive adenylate cyclase in these cells, by 30% at 37 degrees C and almost 50% at 27 degrees C. In contrast, TPA enhances responses to forskolin and cholera toxin at both 27 and 37 degrees C. In membranes from cells treated with TPA, PGE1-stimulated adenylate cyclase activity is inhibited by 50%, whereas the catalytic activity stimulated by NaF or forskolin is enhanced. TPA reduces the potency of both PGE1 and isoproterenol for cAMP generation by 50%. TPA causes a similar decrease in beta-adrenergic agonist affinity with no reduction in the density of either antagonist or agonist binding sites in wild type cells and in cells lacking the alpha-subunit of the stimulatory transducer protein (Gs) (cyc-) or lacking functional receptor Gs coupling (UNC). Therefore, TPA has at least three functionally distinct effects on hormone-sensitive adenylate cyclase in S49 cells: a 50% reduction in agonist affinity, attenuation of receptor-transducer coupling, and enhancement of GTP-dependent catalytic activity. We conclude that multiple and opposing effects of TPA on hormone-sensitive adenylate cyclase occur simultaneously within the same cell, affecting the responses to several agonists differently.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1986

Enhancement of adenylate cyclase activity in S49 lymphoma cells by phorbol esters. Withdrawal of GTP-dependent inhibition.

12-O-Tetradecanoylphorbol-13-acetate (TPA) enhances the apparent maximal velocity of adenylate cyclase in S49 lymphoma cells, an effect that seems not to result from an increased rate of activation of the catalytic subunit by the stimulatory GTP-binding protein (Gs) (Bell, J. D., Buxton, I. L. O., and Brunton, L. L. (1985) J. Biol. Chem. 260, 2625-2628). In membranes from wild type S49 cells, this enhancing effect of TPA is largely GTP-dependent; TPA enhances forskolin-stimulated adenylate cyclase activity by 35% in the presence of guanine nucleotide but only slightly (approximately 10%) in its absence. TPA causes comparable results in membranes from the cyc- variant that lacks the GTP-binding subunit of Gs. Blockade of the activity of the inhibitory GTP-binding protein (Gi) by high concentrations of Mg2+ (100 mM) or Mn2+ (3 mM) abolishes the effect of TPA to enhance adenylate cyclase activity in wild type membranes. The potentiation by TPA of cAMP accumulation in intact cells is greater than and not additive with the similar effect of pertussis toxin (an agent known to abolish hormonal inhibition of adenylate cyclase). Kinetic experiments indicate that TPA decreases the rate of activation of Gi by guanine nucleotide. We conclude that the resultant withdrawal of tonic inhibition of adenylate cyclase is one mechanism by which phorbol esters enhance guanine nucleotide-dependent cAMP synthesis.

Adenylate Cyclase Toxin↗
PubMed1986

1H NMR studies of urine during fasting: excretion of ketone bodies and acetylcarnitine.

High-resolution 1H NMR spectroscopy has been applied to a study of urine from five normal human subjects during a 48-h period of fasting and for 22 h thereafter. The excretion rates of all three ketone bodies (acetoacetate, 3-D-hydroxybutyrate, and acetone), acetylcarnitine, creatinine, and sarcosine during this period were measured. Parallel increases in the excretion of the ketone bodies and acetylcarnitine were observed during fasting with little change in the output of creatinine and sarcosine.

3-Hydroxybutyric Acid↗
PubMed1986

Mechanism-oriented assessment of isotretinoin in chronic or subacute cutaneous lupus erythematosus.

Eight of ten patients with chronic or subacute cutaneous lupus erythematosus completed 16 weeks of oral isotretinoin therapy (80 mg/day). All eight patients noted an excellent clinical response without significant side effects. (Two patients did not return to initial two-week follow-up.) Peripheral blood B- and T-cell counts were unaffected by therapy. Therapy was associated with resolution of routine histopathologic abnormalities, conversion of abnormal lesional direct immunofluorescence microscopy to normal, normalization of the epidermis on electron microscopy, and reduction of all T cells near the dermoepidermal junction without change in ratio of T-helper/inducer cells to T-suppressor/cytotoxic cells. Isotretinoin is a clinically effective short-term therapy for chronic or possibly for subacute cutaneous lupus erythematosus. The primary mechanism of action remains unestablished.

Administration, Oral↗
PubMed1985

Enhancement of adenylate cyclase activity in S49 lymphoma cells by phorbol esters. Putative effect of C kinase on alpha s-GTP-catalytic subunit interaction.

Addition of 12-O-tetradecanoylphorbol-13-acetate (TPA) to S49 lymphoma cells (wild type and a cyclic AMP-dependent protein kinase-lacking clone) has little effect alone but doubles accumulation of cyclic AMP in response to isoproterenol. The effect is immediate and has an apparent affinity and order of potency characteristic of the activation of protein kinase C by phorbol esters. Enhancement does not reflect an altered time course of the beta-adrenergic response, enhanced affinity of the cellular beta-receptor for agonist, or decreased degradation and export of cellular cyclic AMP. Reduction of the beta-adrenergic response by somatostatin does not remove the effect of TPA nor does TPA abolish the effect of somatostatin. Phorbol ester enhances cyclic AMP accumulation in response to cholera toxin in wild type and UNC clones but not in H21a or cyc-. TPA also enhances cAMP accumulation in response to forskolin in wild type cells. The effect of TPA is stable to rapid preparation of membranes. In adenylate cyclase assays on membranes from cells treated with TPA, the activation by guanosine 5'-(beta, gamma-imino)triphosphate is enhanced by 40% with no change in lag time; the effect of beta-agonist plus Gpp(NH)p is similarly enhanced; activation by Mn2+ is unchanged. We conclude that phorbol ester facilitates the productive interaction of the alpha subunit of the transducer protein Gs with the catalytic unit of adenylate cyclase, hypothetically via an action of protein kinase C.

Adenylyl Cyclases↗
PubMed1984

A kinetic isotope dilution assay for glycerol.

Using glycerol kinase and [3H]glycerol, a kinetic isotope dilution assay for glycerol has been developed. Reactant and product are separated by stepwise elution from QAE-Sephadex. This assay is sensitive to as little as 100 pmol of glycerol, avoids numerous drawbacks of the traditional fluorescent assay, and readily detects glycerol production by fewer than 10(5) cardiomyocytes.

Chromatography, Ion Exchange↗
PubMed1983

Inability of thoracic duct drainage to prevent hyperacute rejection.

Serum and lymph albumin and Ig levels were measured during 6 weeks of lymphocyte depletion by thoracic duct drainage (TDD) in 21 patients prior to renal allotransplantation. In ten of these patients, the amount of protein lost from all sources (blood sampling, dialysis, and lymph centrifugation) was measured. The total amount of albumin lost was significantly greater than the amount of IgG lost. However, serum IgG declined at a faster rate and to a greater extent than albumin. Hyperacute or acute humoral rejection occurred in 14 grafts in 10 patients prepared by TDD despite negative crossmatch tests. These data suggest that removal of lymphocytes by TDD, rather than protein loss alone, affects IgG levels. On the other hand, TDD and IgG depletion do not prevent hyperacute or acute humoral rejection. This is most likely due to the inability of currently employed crossmatch tests to predict accurately which patients will manifest antibody-mediated graft rejection.

Drainage↗
PubMed1981

Renal transplantation after thoracic duct drainage.

Forty-seven patients treated by at least 28 days of thoracic duct drainage (TDD) before cadaveric renal transplant are compared with 63 patients treated with standard immunosuppression. The TDD patients were begun on half the dosage of steroids, and at 30 days were receiving approximately two-thirds the dose that the non-TDD patients received. Acute rejection occurred in 35% of the TDD group, as compared with 61% of the non-TDD group. Graft survival in the TDD patients was twice as good as the non-TDD patients at all time intervals. The patient survival rates were not significantly different between the two groups. TDD pretransplant favorably affects cadaveric renal allograft survival for at least five years.

Adult↗