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M Irving

Publications and source records attributed to M Irving.

At least 19 recordsLinked to original sources

Myosin head movements are synchronous with the elementary force-generating process in muscle.

Motor proteins such as myosin, dynein and kinesin use the free energy of ATP hydrolysis to produce force or motion, but despite recent progress their molecular mechanism is unknown. The best characterized system is the myosin motor which moves actin filaments in muscle. When an active muscle fibre is rapidly shortened the force first decreases, then partially recovers over the next few milliseconds. This elementary force-generating process is thought to be due to a structural 'working stroke' in the myosin head domain, although structural studies have not provided definitive support for this. X-ray diffraction has shown that shortening steps produce a large decrease in the intensity of the 14.5 nm reflection arising from the axial repeat of the myosin heads along the filaments. This was interpreted as a structural change at the end of the working stroke, but the techniques then available did not allow temporal resolution of the elementary force-generating process itself. Using improved measurement techniques, we show here that myosin heads move by about 10 nm with the same time course as the elementary force-generating process.

Actins

Appraisal of percutaneous tracheostomy.

Two commercially available kits have been used to create 25 percutaneous tracheostomies, 20 using the Cook system and five using the Rapitrac system. The operation time and complication rates of these tracheostomies have been compared with those for 16 conventional tracheostomies performed for similar indications. Median operating times were 60 (range 30-105) min for conventional tracheostomy, 15 (range 8-70) min for Cook and 5 (range 3-15) min for Rapitrac systems (P less than 0.001). A significantly higher proportion of patients in the Rapitrac group had complications compared with the other two groups (P less than 0.05). The complication rate for the Cook group compared favourably with that for the conventional tracheostomy group. The Cook system of percutaneous tracheostomy is a simple, rapid and safe alternative to conventional tracheostomy.

Adult

Surgeons and HIV.

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AIDS Serodiagnosis

Hepatic phosphofructokinase-1 activity and fructose 2,6-bisphosphate levels in patients with abdominal sepsis.

1. In sepsis various processes of carbohydrate metabolism, such as hepatic gluconeogenesis and glycolysis, are altered. Phosphofructokinase-1, a key glycolytic enzyme, is controlled in the long term via regulation of synthesis and degradation of the protein itself, while in the short term it is regulated by allosteric effectors, such as fructose 2,6-bisphosphate (the most potent). In the present study hepatic phosphofructokinase-1 activity as well as phosphofructokinase-2 activity and the concentration of fructose 2,6-bisphosphate were assayed to determine if they might contribute to the derangement of carbohydrate metabolism seen commonly in sepsis. 2. The levels of glycogen and fructose 2,6-bisphosphate and the activity of phosphofructokinase-1 and phosphofructokinase-2 were determined in hepatic biopsies obtained at laparotomy from six patients with and seven patients without abdominal septic foci. 3. A significant increase in plasma lactate concentration was observed in the septic patients, whereas no significant differences in tissue glycogen content or plasma glucose concentration were seen between the groups. 4. No significant change in plasma insulin concentration was observed. However, levels of the counter-regulatory hormones (glucagon, cortisol and adrenaline) were elevated in the septic patients. 5. A 60% decrease in hepatic phosphofructokinase-1 activity was seen in the septic patients. However, no significant changes in hepatic phosphofructokinase-2 activity and fructose 2,6-bisphosphate content were observed in the septic patients. 6. The present results demonstrate that the decrease in hepatic phosphofructokinase-1 activity occurring in sepsis does not appear to reflect alterations in the concentration of fructose 2,6-bisphosphate.

Abdomen

Intracellular diffusion in the presence of mobile buffers. Application to proton movement in muscle.

Junge and McLaughlin (1987) derived an expression for the apparent diffusion constant of protons in the presence of both mobile and immobile buffers. Their derivation applies only to cases in which the values of pH are considerably greater than the largest pK of the individual buffers, a condition that is not expected to hold in skeletal muscle or many other cell types. Here we show that, if the pH gradients are small, the same expression for the apparent diffusion constant of protons can be derived without such constraints on the values of the pK's. The derivation is general and can be used to estimate the apparent diffusion constant of any substance that diffuses in the presence of both mobile and immobile buffers. The apparent diffusion constant of protons is estimated to be 1-2 x 10(-6) cm2/s at 18 degrees C inside intact frog twitch muscle fibers. It may be smaller inside cut fibers, owing to a reduction in the concentration of mobile myoplasmic buffers, so that in this preparation a pH gradient, if established within a sarcomere following action potential stimulation, could last 10 ms or longer after stimulation ceased.

Action Potentials

Myosin crossbridge orientation in demembranated muscle fibres studied by birefringence and X-ray diffraction measurements.

Muscle contraction is generally thought to involve changes in the orientation of myosin crossbridges during their ATP-driven cyclical interaction with actin. We have investigated crossbridge orientation in equilibrium states of the crossbridge cycle in demembranated fibres of frog and rabbit muscle, using a novel combination of techniques: birefringence and X-ray diffraction. Muscle birefringence is sensitive to both crossbridge orientation and the transverse spacing of the contractile filament lattice. The latter was determined from the equatorial X-ray diffraction pattern, allowing accurate characterization of the orientation component of birefringence changes. We found that this component decreased when relaxed muscle fibres were put into rigor at rest length, and when either the ionic strength or temperature of relaxed fibres was lowered. In each case the birefringence decrease was accompanied by an increase in the intensity of the (1,1) equatorial X-ray reflection relative to that of the (1,0) reflection. When fibres that had been stretched largely to eliminate overlap between actin- and myosin-containing filaments were put into rigor, there was no change in the orientation component of the birefringence. When isolated myosin subfragment-1 was bound to these rigor fibres, the orientation component of the birefringence increased. The birefringence changes at rest length are likely to be due to changes in the orientation of myosin crossbridges, and in particular of the globular head region of the myosin molecules. In relaxed fibres from rabbit muscle, at 100 mM ionic strength, 15 degrees C, the long axis of the heads appears to be relatively well aligned with the filament axis. When fibres are put into rigor, or the temperature or ionic strength is lowered, the degree of alignment decreases and there is a transfer of crossbridge mass towards the actin-containing filaments.

Adenosine Triphosphate

Intraluminal calcium binding does not mediate fatty acid-induced pancreatic bicarbonate secretion.

Since the chain length dependency of fatty acid-induced pancreatic exocrine secretion parallels that of fatty acid-induced inhibition of gastric emptying, similar mechanisms of action may be involved. An earlier study suggested that binding of calcium might mediate fatty acid-induced inhibition of gastric emptying. This study investigated possible mediation of fatty acid-induced pancreatic secretion by calcium binding. Pancreatic secretory response to intraduodenal administration of dodecanoate and various calcium chelators (sodium EDTA, calcium-saturated EDTA, sodium dodecyl sulfate, sodium dioctyl sulfosuccinate, and sodium taurocholate) was studied in three dogs equipped with chronic pancreatic fistulae. Calcium affinity of the various test solutions was quantitated by titrating aliquots of perfusate against a standard CaCl2 solution. Sodium EDTA was found to be the most potent calcium binder (pKc 8.3); sodium dodecanoate, sodium dodecyl sulfate, and sodium dioctyl sulfosuccinate were moderate calcium binders (pKc 7.3, 7.2, 6.9, respectively), whereas sodium taurocholate and calcium-saturated EDTA were poor calcium binders. Sodium dodecanoate evoked brisk bicarbonate output (0.6-1.6 mEq/15 min). Minimal secretory responses were observed in response to all other agents tested. These findings suggest that calcium binding is not involved in mediation of fatty acid-induced pancreatic bicarbonate secretion.

Animals

Simultaneous monitoring of changes in magnesium and calcium concentrations in frog cut twitch fibers containing antipyrylazo III.

Antipyrylazo III was introduced into frog cut twitch fibers (17-19 degrees C) by diffusion. After action potential stimulation, the change in indicator absorbance could be resolved into two components that had different time courses and wavelength dependences. The first component was early and transient and due to an increase in myoplasmic free [Ca] (Maylie, J., M. Irving, N.L. Sizto, and W.K. Chandler, 1987, Journal of General Physiology, 89:83-143). The second component, usually measured at 590 nm (near the isosbestic wavelength for Ca), developed later than the Ca transient and returned towards baseline about 100 times more slowly. Although the wavelength dependence of this component is consistent with an increase in either free [Mg] or pH, its time course is clearly different from that of the signals obtained with the pH indicators phenol red and 4',5'-dimethyl-5-(and -6-) carboxyfluorescein, suggesting that it is mainly due to an increase in free [Mg]. After a single action potential in freshly prepared cut fibers that contained 0.3 mM antipyrylazo III, the mean peak amplitude of delta A (590) would correspond to an increase in free [Mg] of 47 microM if all the signal were due to a change in [Mg] and all the intracellular indicator reacted with Mg as in cuvette calibrations. With either repetitive action potential stimulation or voltage-clamp depolarization, the delta A (590) signal continued to develop throughout the period when free [Ca] was elevated and then recovered to within 40-90% of the prestimulus baseline with an average rate constant between 0.5 and 1.0 s-1. With prolonged voltage-clamp depolarization, both the amplitude and rate of development of the delta A(590) signal increased with the amplitude of the depolarization and appeared to saturate at levels corresponding to an increase in free [Mg] of 0.8-1.4 mM and a maximum rate constant of 3-4 s-1, respectively. These results are consistent with the idea that the delta A(590) signal is primarily due to changes in myoplasmic free [Mg] produced by a change in the Mg occupancy of the Ca,Mg sites on parvalbumin that results from the Ca transient.

Action Potentials

Magnetic resonance imaging--first human images in Australia.

The use of magnetic resonance imaging, in the demonstration of internal human anatomy and in the diagnosis of disease, has the major advantages that the technique is noninvasive, does not require the use of ionizing radiation and that it can demonstrate neurological and cardiovascular lesions that cannot be diagnosed easily by other imaging methods. Magnetic resonance imaging is derived from the principle that certain atomic nuclei in a strong magnetic field will absorb pulses of radiofrequency energy; when the pulse is finished the nuclei will emit radiowaves at the same frequency. These radiowaves are received by specially designed aerials or coils and the information is collected by a computer which reconstructs an image of internal anatomy in a similar way to that of x-ray computed tomography (CT). By changing the strength of the magnetic fields and the frequency of the radiowave pulses, it is possible to examine different sections within the body. The first magnetic resonance images of humans were obtained in Australia in October 1985 on the research instrument of the Queensland Medical Magnetic Resonance Research Centre, which is based at the Mater Hospital in Brisbane, and is part of the University of Queensland's Department of Radiology.

Abdomen

Home parenteral nutrition in the United Kingdom and Ireland.

Between January, 1977, and March, 1986, 200 patients were registered as receiving home parenteral nutrition (HPN) in the UK and the Republic of Ireland. Although 28 centres contributed case-reports, 75% of the cases were registered by 7 centres. Most patients started treatment between the ages of 10 and 40 years, a reflection of the high incidence of Crohn's disease during these decades. The three main indications for HPN were Crohn's disease (90 patients), mesenteric vascular disease (27), and extensive small-bowel resection for volvulus or other benign enteric disease (14). 85 patients required treatment for less than 1 year and 17 have been on treatment for more than 2 years. Patients whose indication for HPN was a primary intestinal disease had a better quality of life than did those in whom the intestinal failure was secondary to a systemic disorder. Of the 108 patients who have completed treatment 56 have been able to resume enteral nutrition through adaptation of the remaining bowel, or closure of a fistula. 34 have died, 19 as a consequence of the underlying disease and 10 of complications of treatment. The incidence of catheter-related sepsis varied between 0.2 and 0.9 episodes per year of treatment (overall 0.35) depending on the length of experience of the supervising centre.

Adolescent

Intraperitoneal low-pressure suction drainage following splenectomy.

A consecutive series of 282 patients undergoing splenectomy on one surgical unit has been studied to ascertain the incidence of postoperative subphrenic abscess. Only two atypical subphrenic abscesses occurred (0.17 per cent), a rate of abscess formation much lower than that reported in other series. We believe that the use of low-pressure closed suction drainage to the splenic bed accounts for this low rate.

Amylases