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Biomedical subjects

A Hurst

Publications and source records attributed to A Hurst.

At least 19 recordsLinked to original sources

"Safe" Coulomb excitation of 30Mg.

We report on the first radioactive beam experiment performed at the recently commissioned REX-ISOLDE facility at CERN in conjunction with the highly efficient gamma spectrometer MINIBALL. Using 30Mg ions accelerated to an energy of 2.25 MeV/u together with a thin (nat)Ni target, Coulomb excitation of the first excited 2+ states of the projectile and target nuclei well below the Coulomb barrier was observed. From the measured relative deexcitation gamma-ray yields the B(E2;0(+)gs-->2(+)1) value of 30Mg was determined to be 241(31)e2 fm4. Our result is lower than values obtained at projectile fragmentation facilities using the intermediate-energy Coulomb excitation method, and confirms the theoretical conjecture that the neutron-rich magnesium isotope 30Mg resides outside the "island of inversion."

Journal Article↗

Nitric-oxide-induced inhibition of glyceraldehyde-3-phosphate dehydrogenase may mediate reduced endothelial cell monolayer integrity in an in vitro model blood-brain barrier.

The process of nitric-oxide (NO)-induced cellular toxicity may involve energy deprivation since the radical is reported to prevent both mitochondrial oxidative phosphorylation and glycolysis. In order to determine whether these processes are important in NO-induced blood-brain barrier (BBB) dysfunction, we used a cell culture model of the BBB and compared the effects of gaseous NO, potassium cyanide (KCN, a mitochondrial respiratory chain inhibitor) and iodoacetate [IA, an inhibitor of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH)] on endothelial cell ATP content, GAPDH activity and barrier integrity. NO lead to a rapid breakdown in model barrier integrity and resulted in a reduction in endothelial cell ATP content and GAPDH activity. KCN had no effect on endothelial cell ATP content or barrier integrity, while IA, at a concentration that completely blocked endothelial cell GAPDH activity, resulted in a rapid decline in ATP content but did not lead to a decline in barrier integrity until at least 2 h of exposure. These results indicate that inhibition of endothelial cell GAPDH activity rather than mitochondrial respiration causes an energy deficiency and delayed barrier dysfunction. However, the rapid detrimental effects of gaseous NO on barrier integrity cannot be fully explained by endothelial cell energy depletion and may be related to the actions of the free radical and its products on cellular lipids.

Adenosine Triphosphate↗

A unique zinc-binding site revealed by a high-resolution X-ray structure of homotrimeric Apo2L/TRAIL.

Apoptosis-inducing ligand 2 (Apo2L, also called TRAIL), a member of the tumor necrosis factor (TNF) family, induces apoptosis in a variety of human tumor cell lines but not in normal cells [Wiley, S. R., Schooley, K., Smolak, P. J., Din, W. S., Huang, C.-P., Nicholl, J. K., Sutherland, G. R., Smith, T. D., Rauch, C., Smith, C. A., and Goodwin, R. G. (1995) Immunity 3, 673-682; Pitti, R. M., Marsters, S. A., Ruppert, S., Donahue, C. J., Moore, A., and Ashkenazi, A. (1996) J. Biol. Chem. 271, 12687-12690]. Here we describe the structure of Apo2L at 1.3 A resolution and use alanine-scanning mutagenesis to map the receptor contact regions. The structure reveals a homotrimeric protein that resembles TNF with receptor-binding epitopes at the interface between monomers. A zinc ion is buried at the trimer interface, coordinated by the single cysteine residue of each monomer. The zinc ion is required for maintaining the native structure and stability and, hence, the biological activity of Apo2L. This is the first example of metal-dependent oligomerization and function of a cytokine.

Alanine↗

Risks of angiotensin-converting enzyme inhibition during pregnancy: experimental and clinical evidence, potential mechanisms, and recommendations for use.

OBJECTIVE: To review reports on the use of angiotensin-converting enzyme inhibitors (ACE-I) during pregnancy in order to determine the incidence, nature, and potential mechanisms of fetal complications in an attempt to establish recommendations related to the use of these drugs during gestation. DATA SOURCES: Relevant English-language articles identified through a Medline search and bibliographies found in recent articles. STUDY SELECTION: Large number of reports both on animals and on humans have consistently shown a high degree of morbidity and even mortality in fetuses or newborns exposed to ACE-I during pregnancy. The reported complications include oligohydramnios, intrauterine growth retardation, premature labor, fetal and neonatal renal failure, bony malformations, limb contractures, persistent patent ductus arteriosus, pulmonary hypoplasia, respiratory distress syndrome, prolonged hypotension, and neonatal death. A high incidence of fetal complications was related to the use of ACE-I at all trimesters of pregnancy. CONCLUSION: The gestational use of ACE-I may be associated with a high degree of fetal and newborn morbidity and even mortality. The use of these drugs should be avoided at all trimesters of pregnancy.

Abnormalities, Drug-Induced↗

Efficacy, risks, and limits of extracorporeal shock wave lithotripsy for salivary gland stones.

Stones of the salivary glands may cause recurrent swelling, ascending inflammation, and colic-like pain. Previously, in order to get rid of these stones, the gland usually had to be removed surgically in spite of the associated risks to adjacent structures, especially the facial nerve. We treated 104 salivary gland stones in patients 14 to 78 years old using the Storz Modulith SL 10 lithotripter. Each session (average 3.6 per patient) consisted of 1000 impulses at 2 Hz and 16 to 18 kV. No anesthesia was required. Earplugs were applied to patients being treated for parotid gland stones. With the aid of SWL and drug-induced salivation, 17 (59%) of the patients with parotid gland stones and 42 (56%) of those with submandibular gland stones obtained either total stone clearance or sufficient fragmentation to permit spontaneous passage. Four patients required surgery. The remaining patients are still being treated. The noninvasive SWL for salivary gland stones is noninvasive and painless and has a considerable success rate. It can be performed on an outpatient basis.

Acute Disease↗

Biliary lithotripsy with a new electromagnetic shock wave source. A 2-year clinical experience.

During a two-year study period 170 consecutive patients with gallbladder stones, suitable for lithotripsy, were treated with a new electromagnetic lithotriptor (Modulith) and oral bile acids; 142 patients were treated as outpatients. Sufficient fragmentation were obtained in 94% when 2112 +/- 137 shocks in 211 sessions with an energy setting of 17.8 +/- 0.8 kV were administered. Only 4/170 patients needed transient analgesia. Overall, side effects were transient and mild, but three patients developed biliary pancreatitis, which was treated by endoscopic sphincterotomy in two of them. A total of 67/100 patients were free of stones after one year. Subgroup analysis showed that 80% of the patients (stone diameter 5-20 mm), 64% (20-30 mm) and 65% (multiple stones), respectively, can expected to be free of stones after 12 months. In addition, 25 patients with large, endoscopically not extractable common bile duct stones were treated by lithotripsy with the Modulith. After endoscopic placement of a nasobiliary tube, stone targeting was possible by ultrasonography in 14 patients and by fluoroscopy in another 11 cases. In 23 of the 25 patients (92%) stone clearance by endoscopy was achieved after application of 2516 +/- 565 shocks with an energy preset of 18 kV. One patient refused further endoscopic procedures after successful fragmentation and another required local stone dissolution therapy. Side effects occurred more frequently (P < 0.05) after lithotripsy of bile duct stones than of gallbladder stones, but they were without major clinical relevance. The new lithotriptor Modulith thus enables safe and highly effective lithotripsy of gallbladder calculi on an outpatient basis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Plasma cyclic guanosine monophosphate in chronic heart failure: hemodynamic and neurohormonal correlations and response to nitrate therapy.

This study evaluated the relation between plasma cyclic guanosine monophosphate (cGMP) and hemodynamic and neurohormonal parameters in patients with chronic congestive heart failure and assessed the effect of organic nitrate on plasma cGMP levels. Plasma cGMP was fourfold higher in 18 patients with congestive heart failure compared with 15 control subjects (16.7 +/- 9.7 versus 4.0 +/- 1.0 pmol/ml; p < 0.0001) but did not correlate with plasma levels of catecholamines, renin, atrial natriuretic peptide, or with baseline hemodynamic values. The administration of a hemodynamically effective dose of oral isosorbide dinitrate (40 mg) resulted in a transient reduction in plasma cGMP from 16.7 +/- 9.7 pmol/ml at baseline to 13.0 +/- 6.6 pmol/ml at 1 hour (p < 0.05). This change was associated with small and statistically insignificant changes in neurohormonal values and had no relation to any of the hemodynamic changes. We concluded that (1) elevated plasma cGMP in congestive heart failure does not correlate with other neurohormonal or hemodynamic parameters and may be an independent parameter of heart failure, (2) in contrast to previously documented nitrate-mediated increases in intracellular cGMP, nitrate therapy results in a reduction in plasma cGMP, and (3) changes in plasma cGMP cannot serve as a surrogate measurement of changes in intracellular cGMP.

Administration, Oral↗

Electromagnetically generated extracorporeal shockwaves for fragmentation of extra-and intrahepatic bile duct stones: indications, success and problems during a 15 months clinical experience.

Electromagnetically generated extracorporeal shock waves (without waterbath) were applied after intravenous premedication with 10-15 mg diazepam and 100 mg tramadol in the treatment of 33 patients (aged 32 to 91 years) with multiple intrahepatic stones (n = 4) or huge common bile duct stones (n = 29, 18-30 mm in diameter), which could not be removed by conventional endoscopy. Stone disintegration was achieved in 70% of common bile duct stones and in all intrahepatic concrements after 800-7500 discharges, which were applied during one (n = 21), two (n = 6) or three sessions (n = 6). Apart from mild fleabite-like petechiae at the side of shock wave transmission no other side effects were observed for a total of 51 procedures. We believe electromagnetically generated shock waves are safe, easy to apply, and relatively effective in the therapy of common bile duct and intrahepatic stones.

Adult↗

An analysis of closed obstetric malpractice claims.

We reviewed all closed obstetric claims in the records of a major physician-sponsored malpractice insurer that has written policies from 1982 to the present. Of the 54 files closed during the 6.5-year period covered by this study, 21 (39%) involved physician reports of bad outcomes that did not lead to a formal claim. Of the 33 formal claims, 14 (42%) were dismissed, either by the plaintiff's attorney or by the courts. Eighteen of the remaining 19 claims were settled before trial, with an average payment to the plaintiff of $185,000. The one suit that went to trial resulted in a defense verdict. A review of the case histories demonstrated that in the majority of cases when a payment was made, probable medical negligence had taken place. Non-meritorious claims were not compensated. For those cases in which a payment was made, the size of the settlement was commensurate with the seriousness of the injury, which almost always involved damage to the infant. Poor physician judgment was the most common source of error.

Costs and Cost Analysis↗

Adaptational changes in Staphylococcus aureus MF31 grown above its maximum temperature when protected by NaCl: physiological studies.

Staphylococcus aureus MF31 can grow at 46 degrees C, 2 degrees C above its normal maximum temperature of growth if 1 M NaCl is added to the medium. In the present work we show that monosodium glutamate, proline, threonine, aspartic acid, and betaine (in order of decreasing effectiveness) also enabled cells to grow at 46 degrees C. Cells grown at 46 degrees C in he presence of salt (protected or P cells) accumulated glutamate more rapidly than cells grown at 37 degrees C without salt (normal or N cells) and contained an increased amino acid pool. The principal constituents of this pool were dicarboxylic amino acids and proline. Turbidimetric evidence suggests that NaCl caused plasmolysis in S. aureus. The P cells, although grown in 1 M NaCl, had about the same Cl- and K+ content as the N cells grown without added NaCl. P cells had increased heat resistance but high concentrations of CaCl2 in the heating menstruum reduced their D55 value from a maximum of 214 min to less than 30 s. We suggest that growth at 46 degrees C in 1 M NaCl can be explained, in part at least, by the increased amino acid pool internal to the cell and the external osmotic support given by Cl- anions excluded by the cell.

Adaptation, Physiological↗

Adaptational changes in Staphylococcus aureus MF 31 grown above its maximum growth temperature when protected by sodium chloride: lipid studies.

Staphylococcus aureus MF31 was grown to stationary phase in a complex medium at 30, 37, and 43 degrees C in the absence of salt and at 37 and 46 degrees C in the same medium supplemented with 1 M NaCl. The principal phospholipids were cardiolipin, phosphatidylglycerol, aminoacylphosphatidyl glycerol, mono- and di-glycosyldiglyceride, and traces of phosphoglycolipid. The proportion of cardiolipin decreased with increasing growth temperature, but only slightly in the presence of 1 M NaCl, while that of aminoacylphosphatidyl glycerol was unaffected by growth temperature in absence of salt, but was about halved in the presence of 1 M NaCl. The net negative charge per mole phospholipid was greatly increased in the presence of 1 M NaCl. In the absence of salt, temperature had no effect on the total lipid content, but cells from the 46 degrees C culture in 1 M NaCl contained 25% less total lipid. The proportion of phospholipid in the total lipids, both in the absence and presence of salt, declined with increasing growth temperature. The proportion of glycolipids, however, increased with temperature both in the absence and presence of salt. It is suggested that the increase in glycolipid content and in negative charge/mole phospholipid is a part of the adaptation of S. aureus to the combination of high temperature and 1 M NaCl giving its membrane increased stability and possibly helping to exclude Cl- anion from the cell interior.

Chromatography, Thin Layer↗

The protective effect of some food ingredients on Staphylococcus aureus MF31.

The upper limiting temperature of growth of Staphylococcus aureus MF31 in heart infusion broth (HI) was about 44 degrees C but addition of monosodium glutamate (MSG) and soy sauce permitted the organism to grow above this temperature. This effect is similar to that of NaCl. Tomato ketchup, Worcestershire and HP sauces added to HI did not allow growth at the non-permissive temperature of 46 degrees C but death was delayed. Staphylococcus aureus died in unsupplemented chicken meat slurry at 46 degrees C but grew at 48 degrees C in slurry supplemented with 5.8% NaCl and survived incubation for 18 h at 50 degrees C in slurry supplemented with 5.8% NaCl and 5% MSG. Cultures grown at 37 degrees C had a D60 value of 2 min in 50 mmol/l Tris (pH 7.2) buffer. Cultures grown at 46 degrees C in HI containing 5.8% NaCl had a D60 value of 8 min in Tris buffer. Addition of 5.8% NaCl plus 5% MSG to the buffer increased the D60 by a factor of about 7 for both cultures. In storage experiments at room temperature, the culture grown at 37 degrees C and at 46 degrees C plus 5.8% NaCl died at about the same rate in salami. In milk powder, however, the count of 37 degrees C culture decreased from 10% g to 10(6)/g in 5 weeks while the count of 46 degrees C culture remained unchanged. In cottage cheese, freeze-dried rice and macaroni, the 37 degrees C cultures also died more rapidly. It is suggested that cultures grown at 46 degrees C plus 5.8% NaCl may be suitable for experiments with artificially contaminated foods.

Cheese↗