Noise and hearing in industry.
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Biomedical subjects
Publications and source records attributed to N Williams.
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We have examined the hypothesis that insulin insensitivity in hepatic cirrhosis is related to abnormalities of glycogen deposition and skeletal muscle enzyme activities. Otherwise well patients with biopsy-proven hepatic cirrhosis secondary to previous excess alcohol intake were studied. Prior to study, in basal state, patients had identical blood glucose concentrations but raised serum insulin concentrations (cirrhotic: 8.5 +/- 0.8 mU per liter; matched control subjects: 5.7 +/- 0.5 mU per liter, p less than 0.01). Muscle glycogen content, glycogen synthase activity and pyruvate dehydrogenase activity were normal in the basal state. The cirrhotic patients required less glucose to maintain the clamp in response to 0.1 unit per kg per hr insulin (6.7 +/- 0.5 vs. control 8.3 +/- 0.4 mg per kg per min, p less than 0.05) and deposited less glycogen in muscle during the clamp (8.6 +/- 0.5 vs. 12.0 +/- 1.4 mg per gm protein, p less than 0.05). Glycogen deposition correlated with clamp glucose requirement in the cirrhotic patients (r = 0.78, p less than 0.05). The expressed activity of glycogen synthase activity was significantly lower in cirrhotic patients at the end of the clamp (26.5 +/- 1.1% vs. 30.9 +/- 1.6%) and again correlated with clamp glucose requirement (r = 0.82, p less than 0.05). Skeletal muscle pyruvate dehydrogenase activity was not different in patients and control subjects. Insulin insensitivity in hepatic cirrhosis appears to be related to abnormalities of glucose deposition as glycogen in skeletal muscle.
Phosphorylation of proteins in synaptic membranes of rat striatum by endogenous kinases was quantified by scanning the optical density on radioautograms made from gels after electrophoresis of assay samples. Neither the decreased phosphorylation found in samples from morphine-tolerant rats could be raised to control levels, nor could samples from untreated rats be raised to those found after acute opioid administration by the addition of Ca++ and calmodulin to the assay. However, the addition of opioids in vitro to the assay was able to inhibit the stimulation of protein kinase activity by Ca++ and calmodulin. Calmodulin seemed to be transported from membranes to cytosol of striatal synaptosomes from morphine tolerant rats. This phenomenon has been related to striatal dopamine receptor supersensitivity (5, 10), a condition suggested by many kinds of evidence in tolerant animals. After acute administration of etorphine or methionine-enkephalin, the levels of calmodulin were increased in both compartments of striatal synaptosomes. The increased membranal levels may be related to its ease of extraction from the membranes and thus to a physical change in calmodulin.
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Hydrazones of a 6-hydrazinonicotinyl-modified cyclic peptide IIb/IIIa receptor antagonist were prepared in order to protect the hydrazine moiety from reaction with trace aldehyde and ketone impurities encountered during the process of manufacturing and compounding lyophilized kits used in radiolabeling with (99m)Tc. Hydrazones were prepared by either a direct reaction of the 6-hydrazinonicotinyl-modified cyclic peptide with carbonyl compounds or by conjugation of the cyclic peptide with hydrazones of succinimidyl 6-hydrazinonicotinate. Stability of the hydrazones was evaluated by treatment with formaldehyde. Hydrazones derived from simple aliphatic aldehydes underwent an exchange reaction with formaldehyde, while hydrazones of aromatic aldehydes and ketones provided the greatest level of stability when challenged with formaldehyde. We have been successful in protecting 6-hydrazinonicotinyl-modified cyclic peptides from reacting with formaldehyde, while still allowing sufficient reactivity for radiolabeling with (99m)Tc. The hydrazones of succinimidyl 6-hydrazinonicotinate are convenient and general reagents for forming 6-hydrazinonicotinyl conjugates with amino-functionalized bioactive molecules.
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We have identified and partially purified two DNA polymerase activities from purified Trypanosoma brucei mitochondrial extracts. The DNA polymerase activity eluted from the single-stranded DNA agarose column at 0.15 M KCl (polymerase M1) was significantly inhibited by salt concentrations greater than 100 mM, utilized Mg2+ in preference to Mn2+ as a cofactor on deoxyribonucleotide templates with deoxyribose primers, and in the presence of Mn2+ favored a ribonucleotide template with a deoxyribose primer. A 44 kDa peptide in this fraction crossreacted with antisera against the Crithidia fasciculata beta-like mitochondrial polymerase. In activity gels the catalytic peptide migrated at an apparent molecular weight of 35 kDa. The DNA polymerase activity present in the 0.3 M KCl DNA agarose fraction (polymerase M2) exhibited optimum activity at 120-180 mM KCl, used both Mg2+ and Mn2+ as cofactors, and used deoxyribonucleotide templates primed with either deoxyribose or ribose oligomers. Activity gel assays indicate that the native catalytic peptide(s) is approximately 80 kDa in size. The two polymerases showed different sensitivities to several inhibitors: polymerase M1 shows similarities to the Crithidia fasciculata beta-like mitochondrial polymerase while polymerase M2 is a novel, salt-activated enzyme of higher molecular weight.
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Perioperative nursing is a complex arena that involves various roles and procedures. The authors here argue that the key to success is good multidisciplinary communication.