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M J Field

Publications and source records attributed to M J Field.

At least 73 records · Page 4Linked to original sources
PubMed1995

Simulations of electron transfer in the NADPH-bound catalase from Proteus mirabilis PR.

Catalase-bound NADPH both prevents and reverses the accumulation of compound II, an inactive form of catalase that is generated from the normal active intermediate form (compound I) when catalase is exposed to a steady flow of hydrogen peroxide. The mechanism for the regeneration reaction is unknown although NADPH could act either as a one-electron or a two-electron donor. Recently, a reaction scheme has been proposed in which the formation of compound II from compound I generates a neighboring radical species within the protein. NADPH would then donate two electrons, one to compound II for reduction of the iron and the other to the protein free radical. In this paper, we report calculations to find the dominant electron tunneling pathways between NADPH and the heme iron in the catalase from the peroxide-resistant mutant of Proteus mirabilis. Two major tunneling pathways are found which fuse together on Ser-196. It is suggested that the sequence Gly-Ser of the loop that divides the beta 5-strand is the key element for shielding a radical amino acid.

Algorithms↗
PubMed1995

Dental education at the crossroads: a report by the Institute of Medicine.

Today's dental schools confront an environment in higher education and health care that promises less stable financing and, thus, more uncertainty for faculty, students, researchers and administrators. A new report from the Institute of Medicine underscores the need for changes in dental education to prepare for a future that will in many important ways be quite different from the past.

Curriculum↗
PubMed1994

Proximal tubular cell electrolytes during volume expansion in the rat.

1. Proximal tubular intracellular elements were measured by electron microprobe X-ray analysis (a) in rats volume-expanded with albumin-saline in which peritubular oncotic pressure remained normal and (b) in rats in which the renal artery was snared before volume expansion (the early snare model). Glomerular filtration rate and urine Na+ excretion were measured in addition to intracellular Rb+ following a 30 s infusion of RbCl as a marker for K+ transport. 2. In albumin-saline volume-expanded rats, intracellular levels of Na+ ([Na+]i) at 21.5 +/- 0.6 mmol (kg wet wt)-1, Cl- ([Cl-]i) at 18.0 +/- 0.4 mmol (kg wet wt)-1 and Rb+ ([Rb+]i) at 9.4 +/- 0.4 mmol (kg wet wt)-1 were significantly higher (P < 0.0001) than the levels in non-expanded rats ([Na+]i, [Cl-]i and [Rb+]i at 17.7 +/- 0.4, 14.6 +/- 0.3 and 4.7 +/- 0.4 mmol (kg wet wt)-1, respectively; means +/- S.E.M.). The data are consistent with Na+ pump inhibition in the proximal tubule, although this cannot be directly derived from intracellular element measurements. 3. In an early snare model of volume expansion, [Na+]i, intracellular K+ ([K+]i) and [Rb+]i remained unchanged (16.1 +/- 0.4, 131.0 +/- 2.0 and 5.2 +/- 0.3 mmol (kg wet wt)-1, respectively) compared to non-expanded snared kidneys (15.9 +/- 0.6, 131.3 +/- 1.8 and 4.8 +/- 0.3 mmol (kg wet wt)-1, respectively). [Cl-]i at 18.3 +/- 0.5 mmol (kg wet wt)-1 increased (P < 0.0008) compared to controls at 15.8 +/- 0.5 mmol (kg wet wt)-1. Thus, in these rats, evidence for an inhibition of the Na+ pump was no longer observed. This points to a major intrinsic mechanism within the kidney for mediating natriuresis, since circulating factors were identical to those in the unsnared kidney, where significant natriuresis occurred.

Animals↗
PubMed1994

Effects of erythropoietin therapy on the lipid profile in end-stage renal failure.

To evaluate the effects of erythropoietin (EPO) therapy on the lipid profile in end-stage renal failure, we undertook a prospective study in patients on both hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD). One hundred and twelve patients (81 HD, 31 CAPD) were enrolled into the study. Lipid parameters [that is, total cholesterol and the LDL and HDL subfractions, triglycerides, lipoprotein (a), apoproteins A and B], full blood count, iron studies, B12, folate, blood urea, aluminium and serum parathyroid hormone were measured prior to commencement of EPO therapy. Ninety-five patients were reassessed 5.2 +/- 0.3 (mean +/- SEM) months later and 53 patients underwent a further assessment 13.1 +/- 0.6 months after the commencement of EPO, giving an overall follow-up of 10.0 +/- 0.6 months in 95 patients. As expected, EPO treatment was associated with an increase in hemoglobin (7.7 +/- 0.1 vs. 9.9 +/- 0.2 g/dl; P < 0.001) and a decrease in ferritin (687 +/- 99 vs. 399 +/- 69 micrograms/liter; P < 0.01). A significant fall in total cholesterol occurred (5.8 +/- 0.1 vs. 5.4 +/- 0.2 mmol/liter; P < 0.05) in association with a fall in apoprotein B (1.15 +/- 0.04 vs. 1.04 +/- 0.06; P < 0.05) and serum triglycerides (2.26 +/- 0.14 vs. 1.99 +/- 0.21; P < 0.05) during the course of the study. Other lipid parameters did not change, although there was a trend towards improvement.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Effect of atrial natriuretic peptide on cellular element concentrations in rat proximal tubules: evidence for inhibition of the sodium pump.

1. In order to further define the action of atrial natriuretic peptide (ANP) on proximal tubular (PT) transport, combined clearance and electron microprobe X-ray (EMPX) experiments were performed on five male Wistar rats infused with ANP (0.16 nmol/kg per h) and nine control animals. 2. Electron microprobe X-ray analysis of PT cell electrolytes (mmol/kg wet weight) revealed a similar [Na]i in both the control and ANP treated groups (16.4 +/- 0.4 vs 16.5 +/- 0.4; P = 0.894). [Cl]i was lower in the ANP treated animals (14.8 +/- 0.3 vs 12.0 +/- 0.3; P < 0.0001) as was [K]i (131.4 +/- 1.4 vs 114 +/- 1.7; P < 0.0001). The PT cells in the ANP treated group had a significant reduction in dry weight (20.1 +/- 0.3 g% vs 19.0 +/- 0.3 g%; P < 0.024), indicating significant cell swelling. Thus, despite a normal [Na]i, there was net accumulation of Nai following ANP treatment. 3. These results are consistent with accumulation of Nai due to inhibition of the Na pump followed by cell swelling and subsequent regulatory volume decrease with exit of K and Cl. These results are the first to show the effect of ANP on PT intracellular electrolytes.

Animals↗
PubMed1994

Effect of 15-deoxyspergualin on immediate function and long-term survival of transplanted islets in murine recipients of a marginal islet mass.

15-Deoxyspergualin (DSG), a macrophage immunomodulatory agent, was used as a probe in a murine model of islet transplantation to examine 1) the significance of the nonspecific, macrophage-mediated effector arm of beta-cell injury in recipients of a marginal mass of isologous islets by analyzing the duration of temporary posttransplant hyperglycemia, a parameter of immediate beta-cell function; and 2) whether long-term (> 100 days) functional survival could be achieved in recipients of a marginal mass of allogeneic islets. A dose-response study of the number of islets required to ameliorate diabetes showed that 150 isologous islets per recipient resulted in a 75% incidence of cure at a mean of 39.2 +/- 5.8 days posttransplant. DSG-treated (0.625 mg.kg-1.day-1 intraperitoneally) recipients of isologous islets demonstrated a significant (P < 0.01) reduction in the duration of temporary posttransplant hyperglycemia (16.8 +/- 3.2 vs. 39.2 +/- 5.8 days), and DSG-treated recipients of allogeneic islets demonstrated a significant (P < 0.03) improvement in the rate of achieving long-term functional survival (75 vs. 22% in untreated control animals). Finally, identical rates of islet engraftment were found among control animals and DSG-treated animals by measurement of tissue insulin content in transplanted specimens. The results are consistent with the hypothesis that DSG alters the duration of temporary posttransplant hyperglycemia and extends long-term functional survival in murine recipients of a marginal mass of islets, not by affecting the efficiency of islet engraftment, but by suppression of the inhibitory effects on beta-cell function by nonspecific, macrophage mediators.

Animals↗
PubMed1993

Lattice vibrations in crystalline L-alanine.

Zwitterionic L-alanine forms crystals containing strong hydrogen-bonding and methylmethyl interactions. Well-defined low-frequency lattice vibrations exist in the crystals involving correlated intermolecular motions on the picosecond timescale. A characterization of these vibrations is expected to provide useful information on the nature of nonbonded interactions in peptides and proteins. We examine some of the vibrations using coherent inelastic neutron scattering and computer simulation techniques. The neutron scattering measurements are used to determine phonon dispersion relations for the acoustic and some low-frequency optic modes in the crystal. There is evidence for interaction between the two lowest frequency optical phonons and the longitudinal acoustic mode. The velocity of sound is anisotropic and can be correlated with the hydrogen-bonding arrangement in the crystal. Corresponding phonon dispersion relations are derived from normal mode analyses of the crystal using the program CHARMM. Although some calculated vibrational frequencies are somewhat too high, the form of the calculated dispersion relations are in good agreement with experiment.

Alanine↗
PubMed1993

En bloc kidney and whole pancreaticoduodenal transplantation with bladder drainage in the rat: microsurgical technique and outcome.

A microsurgical technique for en bloc kidney and whole pancreaticoduodenal transplantation with bladder drainage employing triple vascular anastomoses without the need for a vascular cuff is described. Nineteen combined isografts were performed using this technique in inbred male Lewis (RT1:I) rats with streptozotocin-induced diabetes. Six recipients died within 1 month from early complications (two from uremia, two from pancreatitis, one from bleeding, one from peritonitis); the other 13 survived more than 1 month after transplantation with both the pancreas and kidney grafts functioning. Four of the 13 rats died after 1 month (one from uremia secondary to an obstructed ureter, one from unexplained uremia, one from peritonitis after a biopsy, and one of unknown causes). The pancreas isografts of two animals were excised at 1 and 3 months to confirm dependence on the graft; both animals became hyperglycemic after graft pancreatectomy and had immediate declines of urine amylase activity to normal. One animal was sacrificed at 3 months to determine the insulin content of its native and transplanted pancreas; insulin was very low in the former and normal in the latter. The remaining rats survived with both grafts functioning for at least 6 months (normoglycemic, high urinary amylase levels, normal or near-normal plasma creatinine concentrations), before being sacrificed within the context of other experiments and for histological observations. Both the kidney and pancreas isografts were well preserved microscopically.(ABSTRACT TRUNCATED AT 250 WORDS)

Anastomosis, Surgical↗
PubMed1993

Compensatory renal hypertrophy: tubular cell growth and transport studied in primary culture.

In order to define the growth and transport characteristics of renal epithelia during hypertrophy, primary culture of proximal tubular cells was established from kidneys of normal rats and those with compensatory renal hypertrophy (CRH) induced by unilateral nephrectomy. At confluence, enhanced growth potential was preserved in the cells derived from the animals with CRH (CRH cells) as compared with cells derived from normal animals (N cells), as evidenced by an increased cellular protein content (250 +/- 12 vs. 151 +/- 11 pg protein/cell; p < 0.001) and a somewhat lesser increase in cellular thymidine incorporation (6,820 +/- 52 vs. 5,151 +/- 308 cpm/10(6) cells; p < 0.02). The cellular Na transport (measured as 22Na uptake) was increased in the CRH cells, being 733 +/- 47, 886 +/- 111, and 1,026 +/- 147 cpm/1,000 cells at 1, 3, and 120 min, respectively, versus 353 +/- 36, 469 +/- 31, and 549 +/- 41 cpm/1,000 cells in N cells (p < 0.05 for each time point), i.e., an increase in Na transport in CRH cells of 107, 88, and 87%, respectively. Addition of Amiloride inhibited Na uptake in N cells by approximately 50% and completely suppressed the excess Na uptake in CRH cells to values observed in normal animals, i.e, 147 +/- 33, 224 +/- 91, and 174 +/- 86 cpm/1,000 cells in CRH cells at 1, 3, and 120 min respectively, versus 181 +/- 71, 164 +/- 57, and 238 +/- 85 cpm/1,000 cells in N cells (p = NS at each time point).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗