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Biomedical subjects

W Vine

Publications and source records attributed to W Vine.

16 recordsLinked to original sources
PubMed1990

Clinical diagnosis by nuclear magnetic resonance spectroscopy. If not now, when?

Nuclear magnetic resonance spectroscopy is the epitome of the high-technology, expensive diagnostic method. Extrapolation from a limited number of patient examinations and from experiments in animal models predicts a bright future for the method. However, several barriers block widespread clinical application in the near future; technical difficulties still exist but they seem to be resolvable in due course. A more serious problem is the absence of an adequate database from which to interpret the vast array of information produced by nuclear magnetic resonance. The necessary understanding of the pathologic biochemistry of disease will be frustratingly slow to appear as will the routine clinical use of magnetic resonance spectroscopy. The critical need for improved diagnostic methods will stimulate experimentation to resolve these problems.

Body Fluids↗
PubMed1989

Injury and recovery of the liver from preservation assessed by 31P NMR spectroscopy: the contrast between preservation with Collins' solution and Ringer's lactate solution.

The biochemistry of hepatic injury and recovery from preservation for transplantation was studied in rat liver perfused in vitro with erythrocytes. ATP and its metabolites, inorganic phosphate (Pi) and pH were quantitated as often as every 2.5 min by 31P NMR spectroscopy during preservation and recovery. Release of the hepatocellular enzymes, lactate dehydrogenase V (LDV) and aspartate aminotransferase (AST) were also measured. The duration of preservation with Collins' solution, the standard clinical preservative, affected the rate of recovery of ATP and monophosphate esters (MP), which include AMP + IMP, and the final recovery of Pi, but not of ATP. The difference between Collins' and Ringer's lactate solution, a poor preservative, became more apparent as preservation time increased. The differences included (1) pH at the end of preservative infusion; (2) pH between 0 and 2.5 min of reperfusion; (3) the MP increase (AMP + IMP) at the end of 13 h of preservation; (4) rate of recovery of ATP after preservation; (5) final ATP recovery during reperfusion; (6) LDV after 13h of preservation. These biochemical differences between good and poor preservation form a rational basis for prediction of liver failure after transplantation and for tests of the quality of new preservatives.

Animals↗
PubMed1987

Effect of endotoxin-induced monokines on glucose metabolism in the muscle cell line L6.

Exposure of fully differentiated L6 myotubes to a crude monokine preparation from endotoxin-stimulated RAW 264.7 cells resulted in a rapid and substantial (70%) increase in fructose 2,6-bisphosphate concentration coincident with a depletion of cellular glycogen and an increased lactate production. During the time required for glycogen depletion (3 hr), stimulation of 3-O-methyl-D-glucose and 2-deoxy-D-glucose uptake was initiated and observed to reach a maximum enhancement of 200% 12-15 hr later. The monokine had no effect on the Km value for 2-deoxy-D-glucose uptake (1.1 mM), while Vmax was increased from 912 to 2400 pmol/min per mg of protein. The increase was cytochalasin B inhibitable and was dependent on protein synthesis. Photoaffinity labeling and equilibrium binding studies with [3H]cytochalasin B support the hypothesis that this increase in hexose transport was due to an increase in hexose transporters present in the plasma membrane. Purified recombinant interleukin-1 alpha had no effect on hexose transport, whereas purified recombinant cachetin/tumor necrosis factor did stimulate hexose uptake, with half-maximal stimulation occurring at 36 nM. Although cachetin accounts for most of the biological activity associated with the crude monokine preparations, it is not the only monokine capable of inducing glucose transport in L6 cells. Specific immunoabsorption of cachectin/tumor necrosis factor from the crude monokine preparation revealed a monokine that had a similar bioactivity at extremely low concentrations on L6 cells.

3-O-Methylglucose↗
PubMed1987

Cyclosporine: structure, pharmacokinetics, and therapeutic drug monitoring.

Cyclosporine is an 11-amino acid cyclic peptide immunosuppressant that has revolutionized organ transplantation. Alone or in combination with prednisone and azathiaprine, it is preferred in hepatic, cardiac, and high-risk renal transplantation. Its unusual primary structure of hydrophobic, N-methylated amino acids results in a compact conformation in the crystal which changes to multiple conformations in hydrophilic solvents. The unusual structure produces unusual pharmacokinetic behavior which is still poorly understood. The metabolism occurs predominately in the liver and is affected by several drugs known to alter hepatic metabolism. At least ten metabolites have been identified but are inadequately characterized. The unique behavior of cyclosporine necessitates therapeutic drug monitoring (TDM) for individualization of therapy. Cyclosporine has been monitored in both whole blood and plasma by both RIA and HPLC with significantly different results for each combination. When cyclosporine is assayed by HPLC in a compulsive regimen of TDM, a correlation is observed between immunosuppression, toxicity, and concentration. To distinguish renal or hepatic toxicity from rejection, biopsies, clinical status, and blood concentrations of cyclosporine must be simultaneously analyzed. After extensive experimental and clinical study, cyclosporine remains an enigma with clear clinical benefit.

Autoimmune Diseases↗
PubMed1986

Effects of cyclosporine and cortisone on the pathogenesis of primary infection with cytomegalovirus in the guinea pig.

Effects of the immunosuppressive agents cyclosporine (CsA) and cortisone on the pathogenesis of primary infections with cytomegalovirus (CMV) were investigated in the guinea pig model. All animals received 10(4) 50% tissue culture infectious doses of virulent salivary gland-passaged guinea pig CMV (GPCMV) subcutaneously on day 0. Oral CsA (20 mg/kg per day) and/or subcutaneous cortisone (10 mg/kg per day) were administered until the animals were killed on day 14. Untreated controls developed lymphocytosis, and GPCMV was isolated from 19.4% of cocultivated tissues. Animals treated with CsA alone developed lymphopenia, and GPCMV was isolated from 53% of their tissues, including 16 of 16 lungs. Histopathology showed widespread viral inclusions and minimal inflammatory response to GPCMV in CsA-treated animals. Guinea pigs treated with either cortisone or CsA/cortisone did not develop lymphopenia, and their rates of isolation of GPCMV were significantly lower than those of CsA-treated animals.

Animals↗
PubMed1986

Relationships of cyclosporine concentrations in serum, whole blood, and bile after renal and hepatic transplantation.

"Trough" (minimum inter-dose) cyclosporine concentrations were measured by liquid chromatography in samples of serum and whole blood or bile obtained from renal- and hepatic-transplant patients. Overall, concentrations in whole blood correlated poorly with concentrations in concurrently obtained serum. The poor correlation also held for individual patients over time. The degree of variability observed for individuals is especially disconcerting. Although cyclosporine measurements in whole blood may mitigate time- and temperature-dependent changes in the drug's distribution after collection, concentrations in serum separated after distribution are less dependent on the cellular mass in blood, and may better reflect the amount of drug available to receptor sites. This consideration may be particularly important in the postoperative period, when fluctuations in the cellular mass of blood are frequent. Concentrations of cyclosporine were also determined in concurrently collected bile and serum samples after liver transplantation. Concentrations of unchanged drug in bile were variably higher than those in serum. Bile/serum concentration ratios ranged from 65/1 to 4.6/1. It is postulated that bile/blood concentration ratios may reflect liver function.

Bile↗
PubMed1985

Effects of cyclosporine on the pathogenesis of primary cytomegalovirus infection in the guinea pig.

The effects of cyclosporin A (CsA) upon the pathogenesis of primary cytomegalovirus (CMV) infection were investigated. Hartley and strain 2 guinea pigs were inoculated subcutaneously on day 0 with 10(4) TCD50 of virulent, salivary-gland-passaged guinea pig CMV and received oral CsA (20 mg/kg/day) for 14 days. CMV-infected, CsA-treated animals lost approximately 20% of their total body weight in 14 days and had more than twice the rate of CMV isolation from internal organs when compared with untreated controls, despite similar rates of viremia. Internal organs of CsA-treated animals demonstrated widespread viral inclusions and minimal inflammatory response to the presence of CMV-infected cells. The mean change in peripheral blood lymphocyte values for CMV-infected, CsA-treated Hartley guinea pigs was -2,867 +/- 2,955 (mean +/- SD) lymphocytes/microliters as compared to +10,933 +/- 7,583 in CMV-infected, untreated controls (p less than 0.01). In the guinea pig model, CsA administration had adverse effects upon the pathogenesis of primary CMV infection.

Animals↗
PubMed1985

Lipopolysaccharide-treated RAW 264.7 cells produce a mediator that inhibits lipoprotein lipase in 3T3-L1 cells.

RAW 264.7 cells upon stimulation with lipopolysaccharide secrete a protein mediator(s) that suppresses lipoprotein lipase activity in differentiated 3T3-L1 cells. The mediator(s), which is absent from unstimulated culture supernatants, is nondialyzable and thermolabile. Preliminary characterization suggests that this mediator(s) may be the same as that previously found in medium from lipopolysaccharide-treated thioglycollate-elicited mouse peritoneal macrophage cultures.

Adipose Tissue↗
PubMed1970

A specific competitive inhibitor of angiotensin II.

A peptide analog, [4-phenylalanine, 8-tyrosine]-angiotensin II, was prepared by solid phase peptide synthesis and its structure confirmed. The compound was found to be a potent inhibitor of angiotensin II in vitro (isolated rat uterus strips) and in vivo (rat blood pressure). The analog was found to be highly specific and did not inhibit the action of a number of other peptides and spasmogenic compounds.

Angiotensin II↗