Quantum and thermal effects in H2 dissociative adsorption: Evaluation of free energy barriers in multidimensional quantum systems.
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Journal Article↗
Biomedical subjects
G Mills
Publications and source records attributed to G Mills.
Inspiratory muscle relaxation rate assessed from sniff nasal pressure.
BACKGROUND: Slowing of the maximum relaxation rate (MRR) of inspiratory muscles measured from oesophageal pressure (POES) during sniffs has been used as an index of the onset and recovery of respiratory muscle fatigue. The purpose of this study was to measure MRR at the nose (PNASAL MRR), to investigate its relationship with POES MRR, and to establish whether PNASAL MRR slows with respiratory loading. METHODS: Five normal subjects were studied. Each performed sniffs before and after two minutes of maximal isocapnic ventilation (MIV). In a separate session the subjects performed submaximal sniffs. POES and PNASAL were recorded during sniffs and the MRR (% pressure fall/10 ms) for each sniff was determined. RESULTS: Before MIV mean POES MRR was 8.9 and PNASAL MRR was 9.3. The mean (SD) difference between PNASAL MRR and POES MRR during a maximal sniff was 0.48 (0.34) (n = 64) and during submaximal sniffs was 0.28 (0.46) (n = 526). The subjects showed a mean decrease in sniff POES MRR of 27.4% (range 22.5-36%) after MIV and a similar reduction in sniff PNASAL MRR of 28.5% (range 24.1-41.3%). Both returned to control values within 5-10 minutes. CONCLUSIONS: PNASAL MRR reflects POES MRR over a wide range of sniff pressures, PNASAL MRR of maximal sniffs reflects POES MRR in normal subjects at rest and following MIV, so measurement of PNASAL MRR may be a useful non-invasive method for measuring inspiratory muscle MRR, thereby providing an index of respiratory muscle fatigue.
Air Pressure↗
Interim life safety.
The field of life safety was developed by concerned individuals looking for a common cause in the loss of life during fires. Creating a safe building environment became their goal, which was partially achieved by studying egress, stairs, fire detection devices, and general occupancy. As long as the building design remains unchanged, the integrity of life safety remains. However, as buildings are subjected to renovation (both planned and unplanned), the integrity of life safety may diminish during the project. This decrease in life safety resulted in the creation of interim life safety measures. This document examines appropriate interim life safety measures.
Building Codes↗
Cell cycle dependent regulation of the protein kinase TTK.
TTK is a novel protein kinase detectable in all proliferating human cells and tissues. Expression of the TTK gene is markedly reduced or absent in resting cells and in tissues with a low proliferative index. In view of the apparent association between TTK gene expression and cell proliferation, we examined the regulation of this protein kinase during transit of the cell cycle. We found very low levels of TTK mRNA and protein in starved cells. When cells are induced to enter the cell cycle, levels of TTK mRNA, protein and kinase activity increase at the G1/S phase of the cell cycle and peak in G2/M. TTK mRNA levels, as well as kinase activity, drop sharply in early G1, whereas protein levels are largely maintained. TTK may play a role in cell cycle control.
Cell Cycle↗
Is cost-awareness really improving?
The findings of a comparative study of cost awareness amongst particular groups of health service staff are reported. The study is a repeat of that undertaken in 1987 by Fairbrass and Chaffe. The findings are compared to assess how awareness of the cost of anaesthetic drugs, fluids and disposables has changed as a result of the publicity since 1987. Without prior warning, the study group were asked to estimate the cost of twenty-eight items. The results show that their degree of accuracy remains poor. Overall the tendency was to overestimate costs, whilst a small number of expensive items such as volatile agents were consistently underpriced. The results show that, over the last three years, there has been no significant change in the knowledge of cost awareness. At a time when the effective use of scarce resources is being emphasised, a staff programme of continuing cost awareness training is recommended.
Anesthesiology↗
Tyrosine kinase-dependent lymphocyte signaling during allograft rejection.
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Analysis of Variance↗
Phase II trial of amonafide in previously treated patients with advanced ovarian cancer: a Southwest Oncology Group study.
Twenty-three patients with metastatic or recurrent Stage III or IV epithelial ovarian cancer who were refractory to or relapsed following previous chemotherapy with cisplatin or a cisplatin analog were entered into a phase II study of amonafide. The starting dose of amonafide was 300 mg/m2 delivered daily over 1 hr by intravenous infusion. In the absence of myelosuppression, the dose of amonafide was escalated by increments of 75 mg/m2 to a maximum of 450 mg/m2. There were 19 eligible and 17 fully evaluable patients. Grade 3 or 4 leukopenia occurred in 14 (74%) patients and grade 3 or 4 thrombocytopenia in 6 (32%) patients. No objective complete or partial responses were observed. Four patients had stable disease for 3, 4, 4.5, and 6 months, respectively. Therefore, amonafide in the doses used in the present trial does not have significant activity in previously treated patients with ovarian cancer.
Adenine↗
Conservative treatment of an incomplete longbone fracture of a hindlimb of four horses.
Four horses with an incomplete fracture of a hindlimb longbone were examined. In two, the tibia had been fractured by external trauma. In the other two horses proximal metatarsal 3 had fractured during normal activity. The diagnoses were made radiographically and the horses were treated conservatively by box rest. The fractures healed satisfactorily and the horses became sound.
Animals↗
End stage renal disease serum contains a specific renal cell growth factor.
End stage renal disease (ESRD) kidneys display abnormal growth characterized by a continuum of cystic disease, adenoma and carcinoma. This study evaluates the hypothesis that serum of patients with ESRD contains increased amounts of a growth factor which specifically induces proliferation of renal cells. ESRD sera compared to sera from normal controls induced a two to three-fold increase in the proliferative rate of renal cell carcinoma cell lines and normal kidney explants compared to cell lines from other sites. The increased proliferative activity of ESRD sera on renal cells was paralleled by an increase in cytosolic free calcium. The growth factor activity was encoded by a polypeptide of between 15 and 30 kd. The activity of ESRD sera on renal cells was not mimicked or inhibited by epidermal growth factor, basic fibroblast growth factor and platelet derived growth factor indicating that the renal cell specific growth factor activity in ESRD is different from these factors.
Calcium Radioisotopes↗
Inverse correlation between tyrosine phosphorylation and collagenase production in chondrocytes.
Collagenase production by chondrocytes appears to play a major role in the development of osteoarthritis. Although the mechanisms regulating collagenase production by chondrocytes are not known, incubation of bovine chondrocytes in serum markedly decreases collagenase production. Since serum has been demonstrated to increase levels of phosphotyrosine (P-Tyr) in several cell types, we determined the effect of altering intracellular levels of P-Tyr on collagenase production. Both orthovanadate, a potent inhibitor of tyrosine phosphatases, and serum caused a marked increase in tyrosine phosphorylation. The increase in P-Tyr was associated with a decrease in the production of collagenase, suggesting that two processes may be linked. Orthovanadate caused an increase in P-Tyr in the absence of serum, suggesting that P-Tyr levels in resting chondrocytes are regulated through activity of both tyrosine kinases and phosphatases. Orthovanadate and serum induced a synergistic increase in P-Tyr levels, suggesting that serum functions through increasing kinase activity rather than decreasing phosphatase activity. In the absence of serum, concentrations of orthovanadate which maximally inhibited collagenase production primarily increased phosphorylation of a 36 kDa protein, suggesting that the phosphorylation of this protein may play a major role in regulating collagenase production. Orthovanadate had limited effects on chondrocyte proteoglycan synthesis, morphology or viability in the presence or absence of serum, suggesting that the decrease in collagenase production was not due to non-specific inhibition of protein synthesis or cellular toxicity. Inhibition of tyrosine phosphatases by orthovanadate or activation of tyrosine kinases by addition of serum correlated with the inhibition of collagenase production.
Animals↗
Expression of ras oncogene leads to down-regulation of protein kinase C.
The effect of mutated c-Ha-ras expression on Ca2+ and phospholipid-dependent protein kinase C (PKC) activity during the process of transformation was analysed using an inducible metallothionein-ras hybrid oncogene system. A close correlation was found between the timing of ras expression and the loss of PKC enzymatic activity measured in a cell-free system. Examination of the subcellular distribution of the enzyme in inducible and constitutive ras-transformants revealed that expression of ras was associated with an apparent translocation of PKC to the plasma membrane concomitant with down-regulation of PKC enzymatic activity in particulate as well as cytosolic fractions. Quantitation of PKC protein utilizing a PKC-specific antiserum showed that ras expression was associated with a decrease in the total amount of PKC protein present in the cell. We conclude that transformation by c-Ha-ras is accompanied by down-regulation of PKC activity and that the basis of this effect may, to a large extent, lie in the down-regulation of the amount of PKC protein.
Animals↗
Identification of a novel glycoprotein (AGp110) involved in interactions of rat liver parenchymal cells with fibronectin.
We have identified an integral membrane glycoprotein in rat liver that mediates adhesion of cultured hepatocytes on fibronectin substrata. The protein was isolated by affinity chromatography of detergent extracts on wheat germ lectin-Agarose followed by chromatography of the WGA binding fraction on fibronectin-Sepharose. The glycoprotein (AGp110), eluted at high salt concentrations from the fibronectin column, has a molecular mass of 110 kD and a pI of 4.2. Binding of immobilized AGp110 to soluble rat plasma fibronectin required Ca2+ ions but was not inhibited by RGD peptides. Fab' fragments of immunoglobulins raised in rabbits against AGp110 reversed the spreading of primary hepatocytes attached onto fibronectin-coated substrata, but had no effect on cells spread on type IV collagen or laminin substrata. The effect of the antiserum on cell spreading was reversible. AGp110 was detected by immunofluorescence around the periphery of the ventral surface of substratum attached hepatocytes, and scattered on the dorsal surface. Immunohistochemical evidence and Western blotting of fractionated liver plasma membranes indicated a bile canalicular (apical) localization of AGp110 in the liver parenchyma. Expression of AGp110 is tissue specific: it was found mainly in liver, kidney, pancreas, and small intestine but was not detected in stomach, skeletal muscle, heart, and large intestine. AGp110 could be labeled by lactoperoxidase-catalyzed surface iodination of intact liver cells and, after phase partitioning of liver plasma membranes with the detergent Triton X-114, it was preferentially distributed in the hydrophobic phase. Treatment with glycosidases indicated extensive sialic acid substitution in at least 10 O-linked carbohydrate chains and 1-2 N-linked glycans. Immunological comparisons suggest that AGp110, the integrin fibronectin receptor and dipeptidyl peptidase IV, an enzyme involved in fibronectin-mediated adhesion of hepatocytes on collagen, are distinct proteins.
Amino Acid Sequence↗
Peripherally acting enkephalin analogues. 2. Polar tri- and tetrapeptides.
The design, synthesis, and biological activity of a series of D-Arg2-enkephalin-derived tetrapeptide amides and tripeptide aralkylamides are reported. These polar analogues were designed to be excluded from the central nervous system with their action thus limited to peripheral opioid receptors. The effects of the nature of the aromatic ring, aryl ring substitution, and aralkylamine chain length on activity were investigated; in a number of cases the N-terminal amino group of Tyr1 was converted to a guanidino group to further increase hydrophilicity. The peptides were all synthesized by classical solution methodology. The opioid activity of the peptides was assessed in vitro on the guinea pig ileum and their antinociceptive activity was determined in vivo in chemically induced writhing models (peripheral activity) and in the hot-plate test (central activity), in rodents. That the analgesic effects were predominantly mediated in the periphery was demonstrated by antagonism of antinociception by the peripheral opioid antagonist N-methylnalorphine and by comparison of the activities in the writhing and hot-plate tests. As a class, the tetrapeptides were more potent than the tripeptides; N alpha-amidination generally increased activity. A number of compounds exhibited very potent opioid activity and had the desired pharmacological profile, indicating a high degree of peripheral selectivity.
Analgesia↗
Physiological role of HMG-CoA reductase in regulating egg production by Schistosoma mansoni.
Pathological lesions observed in humans infected with Schistosoma mansoni are due to the eggs produced by the female parasite. Mevinolin, a potent inhibitor of the enzyme hydroxymethylglutaryl-CoA (HMG-CoA) reductase, blocks egg production by this parasite. In this report, we demonstrate that cholesterol precursors, mevalonate and farnesol, stimulate egg production by the female parasite and that these precursors can reverse the mevinolin-induced inhibition of egg production. Because the parasite cannot synthesize cholesterol, we incubated parasites in a culture media containing radiolabeled acetate with and without mevinolin. We isolated nonsterol lipids from the parasite and observed that mevinolin dramatically reduced the conversion of acetate into the polyisoprenoid (dolichols) lipids of the parasite. Dolichols and other nonsterol lipids did not stimulate egg production. HMG-CoA reductase activity was observed in homogenates of the parasite and was inhibited by mevinolin (Ki = 52 nM), but its activity was tripled when the parasite was chronically exposed to low doses of the drug. Parasites with increased reductase activity produced five to six times more eggs. Lastly, chronic administration of large doses of mevinolin to infected mice resulted in a marked reduction of the pathology associated with the infection. These results suggest that egg production in S. mansoni is associated with the parasite's HMG-CoA reductase activity and that a nonsterol lipid produced in the biochemical pathway regulated by this enzyme stimulates egg production.
Animals↗
Prostaglandins inhibit proliferation of the murine P815 mastocytoma by decreasing cytoplasmic free calcium levels [( Ca+2]i).
Prostaglandins inhibit the proliferation of the murine P815 mastocytoma. The mechanism of this antitumour activity remains undefined. In several cell systems, the action of PGs is inhibited at the cell surface receptor by pertussis toxin likely through regulatory G proteins involved in the inhibition of adenyl cyclase or activation of phospholipase C. We therefore determined the effect of prostaglandins on the biochemical consequences of activation of these pathways; i.e. concentrations of cyclic AMP (cAMP) and cytosolic free Ca+2 concentrations [( Ca/2]i) respectively. PGD2 (6 ug/mL), PGE1 (10 ug/mL) and PGB1 (50 ug/mL) maximally inhibited (3H)-thymidine incorporation to DNA. PGF2 alpha did not affect DNA synthesis. PGE1 (10 ug/mL) induced a three fold increase in cAMP concentrations. In contrast, the other prostaglandins did not alter cAMP concentrations. Maximal growth inhibitory doses of PGD2, PGE1 and PGB1 decrease [Ca+2]i, as measured by the fluorescence of Indo-1, from 320 +/- 5 nM to 172 +/- 20 nM, 161 +/- 12 nM, and 151 +/- 18 nM respectively. PGF2 alpha did not alter [Ca+2]i. Therefore, in contrast to the effects on cAMP, the decrease in [Ca+2]i was concordant with the inhibition of DNA synthesis. This suggests that PGs may inhibit proliferation through decreasing [Ca+2]i in the P815 mastocytoma.
Algorithms↗
The regulatory role of interleukin 2-responsive T lymphocytes on human marrow granulopoiesis.
The effect of recombinant interleukin 2 (IL2) on marrow CFU-C colony formation was evaluated to define the role for T lymphocytes in human marrow granulopoiesis. The colony-stimulating factor (CSA) used in our experiments was found to contain IL2. IL2 depletion from CSA resulted in a reduction in CFU-C colony proliferation. Addition of exogenous IL2 caused an increase in CFU-C colony numbers in a dose-dependent manner. This increase could be prevented by anti-Tac, a monoclonal antibody (MoAb) to the IL2 receptor. Moreover, anti-Tac in the absence of exogenous IL2 resulted in an overall decrease in colony numbers. Depletion of either adherent cells or T lymphocytes abolished the effect of IL2 and anti-Tac on colony growth. In the presence of IL2, re-addition of T lymphocytes to the T-depleted marrow or adherent cells to adherent cell-depleted marrow resulted in a significant increase in CFU-C colony numbers, whereas no significant effect was found when IL2-depleted CSA was used. Although T lymphocytes were not themselves essential for CFU-C colony growth, our studies indicate that IL2 and IL2-responsive T cells can regulate in vitro granulopoiesis.
Antibodies, Monoclonal↗
Phase II evaluation of diaziquone in pancreatic carcinoma: a Southwest Oncology Group Study.
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Adenocarcinoma↗