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Biomedical subjects

M Irving

Publications and source records attributed to M Irving.

At least 55 records · Page 3Linked to original sources
PubMed1996

Fluorescent probes of the orientation of myosin regulatory light chains in relaxed, rigor, and contracting muscle.

The orientation of the light-chain region of myosin heads in relaxed, rigor, and isometrically contracting fibers from rabbit psoas muscle was studied by fluorescence polarization. Cysteine 108 of chicken gizzard myosin regulatory light chain (cgRLC) was covalently modified with iodoacetamidotetramethylrhodamine (iodo-ATR). Native RLC of single glycerinated muscle fibers was exchanged for labeled cgRLC in a low [Mg2+] rigor solution at 30 degrees C. Troponin and troponin C removed in this procedure were replaced. RLC exchange had little effect on active force production. X-ray diffraction showed normal structure in rigor after RLC exchange, but loss of axial and helical order in relaxation. In isolated myofibrils labeled cgRLC was confined to the regions of the sarcomere containing myosin heads. The ATR dipoles showed a preference for orientations perpendicular to the fiber axis, combined with limited nanosecond rotational motion, in all conditions studied. The perpendicular orientation preference was more marked in rigor than in either relaxation or active contraction. Stretching relaxed fibers to sarcomere length 4 microns to eliminate overlap between actin- and myosin-containing filaments had little effect on the orientation preference. There was no change in orientation preference when fibers were put into rigor at sarcomere length 4.0 microns. Qualitatively similar results were obtained with ATR-labeled rabbit skeletal RLC.

Animals↗
PubMed1996

Orientation changes in myosin regulatory light chains following photorelease of ATP in skinned muscle fibers.

The orientation of the light-chain region of myosin heads in muscle fibers was followed by polarized fluorescence from an extrinsic probe during tension transients elicited by photolysis of caged ATP. Regulatory light chain from chicken gizzard myosin was covalently modified with iodoacetamidotetramethylrhodamine and exchanged into skinned fibers from rabbit psoas muscle without significant effect of the tension transients. Fluorescence polarization ratios Q parallel = (parallel I parallel-perpendicular I parallel)/ (parallel I parallel+perpendicular I parallel) and Q perpendicular = perpendicular I perpendicular - parallel I perpendicular)/ (perpendicular I perpendicular + parallel I perpendicular), where mIn denote fluorescence intensities for excitation (pre-subscript) and emission (post-subscript) parallel or perpendicular to the fiber axis, were simultaneously measured at 0.5 ms time resolution. Q perpendicular decreased and Q parallel increased promptly after ATP release in the presence or absence of CA2+, indicating changes in orientation of the light-chain region associated with ATP binding or cross-bridge detachment. Little further change in the Q signals accompanied either active tension development (+Ca2+) or the final relaxation (-Ca2+). The Q and tension transients slowed when liberated ATP concentration was reduced. Assuming that ATP is released at 118 s-1 (20 degrees C), the apparent second-order rate constants were 3-10 x 10(5) M-1 s-1 for Q parallel, 1-5 x 10(5) M-1 s-1 for Q perpendicular, and 0.5-2 x 10(5) M-1 s-1 for the convergence of tension traces starting from different rigor values. Fitting of model orientation distributions to the Q signals indicated that the angular disorder increases after ATP binding. This orientation change is specific to ATP because photo release of ADP caused much smaller changes in the Q signals.

Adenosine Diphosphate↗
PubMed1996

Long-term glucose homeostasis in patients on home parenteral nutrition.

Glycated haemoglobin (Hb A1c) was used as a marker of long-term hyperglycaemia in patients receiving high glucose loads for home parenteral nutrition (HPN). Thirty-six patients received a median weekly glucose delivery of 2000 g (800-4200) at a median infusion rate of 11.8 mg/kg/min (5.0-19.2). There was no correlation between Hb A1c (median- 3.1%, range 2.0-6.3%) and glucose infusion rate or weekly glucose load. It is concluded that significant prolonged hyperglycaemia does not appear to be a problem in patients on HPN managed by this unit.

Journal Article↗
PubMed1996

Investigation of anal function in patients with systemic sclerosis.

OBJECTIVE: To investigate anorectal function in women patients with systemic sclerosis (SSc), with and without lower gastrointestinal symptoms. METHODS: Anorectal manometry was performed in 16 patients with SSc: six with no or minimal bowel symptoms, seven with constipation, and three with diarrhoea and faecal incontinence. Eleven healthy women acted as control subjects. Pressure data were recorded via an eight lumen polyvinylchloride water perfused catheter. Station and rapid pull through techniques were used. RESULTS: In the patients with SSc, mean resting pressure, maximal voluntary squeeze effort, and squeeze vector volume were lower, and squeeze asymmetry was greater, compared with the healthy controls. Differences were significant in the subgroup with constipation. CONCLUSION: Radial asymmetry and vector volume parameters provide detailed analysis of segmental anal canal function. Our findings suggest significant segmental deficits in those patients with SSc who have lower gastrointestinal symptoms. The trend towards smaller pressures and squeeze vector volumes in the asymptomatic SSc group suggests subclinical dysfunction in these patients.

Adult↗
PubMed1996

General practice blood pressure recording in Scotland: variations in the classification of hypertension.

A questionnaire concerning blood pressure assessment, as part of health promotion activity, was circulated to all 770 Gpass practices in Scotland producing a 64.6% response rate. The results reveal a wide range in both the systolic and diastolic levels chosen to classify blood pressure as normal, borderline raised or raised. Practices are using a variety of values to indicate hypertension when considering systolic and, to a lesser extent, diastolic pressure. The variations found suggest that both over and under treatment are a significant risk to patients. The introduction of the 1993 health promotion regulations means that practices are required to actively target their practice population for blood pressure assessment and appropriate intervention. We suggest that this process will be enhanced if doctors are encouraged to adopt the established guidelines for the classification of blood pressure or general practice computer software is adopted to offer blood pressure protocol support.

Adolescent↗
PubMed1995

Tilting of the light-chain region of myosin during step length changes and active force generation in skeletal muscle.

Force generation and relative sliding between the myosin and actin filaments in muscle are thought to be caused by tilting of the head region of the myosin crossbridges between the filaments. Structural and spectroscopic experiments have demonstrated segmental flexibility of myosin in muscle, but have not shown a direct linkage between tilting of the myosin heads and either force generation or filament sliding. Here we use fluorescence polarization to detect changes in the orientation of the light-chain region of the head, the part most likely to tilt, and synchronized head movements by imposing rapid length steps. We found that the light-chain region of the myosin head tilts both during the imposed filament sliding and during the subsequent quick force recovery that is thought to signal the elementary force-generating event.

Animals↗
PubMed1995

Elastic distortion of myosin heads and repriming of the working stroke in muscle.

Muscle contraction is driven by a cyclical interaction between the globular head domain of myosin and the actin filaments. We used quick stretches of 5 nm per half sarcomere to synchronize the movements of myosin heads in active single muscle fibres. The intensity of the 14.5 nm X-ray reflection decreased during the stretch, showing that the instantaneous elasticity of muscle involves distortion of myosin heads. Head movement continued at about 1,500 s-1 after the stretch, accompanied by partial force recovery. This indicates a reversal of the force-generating 'working stroke' in the myosin heads that is smaller and faster than assumed previously. By 50 ms after the stretch, myosin heads have regained both their original conformation and the ability to execute a normal working stroke. This 'repriming' process is slower than that following shortening but much faster than the ATP turnover rate per myosin head.

Animals↗
PubMed1995

Manometric asymmetry in the anal canal in controls and patients with fecal incontinence.

PURPOSE: This study was designed to ascertain the existence of manometric asymmetry in the anal canal in controls and in patients with fecal incontinence. METHODS: A computerized manometric technique with an eight-channel perfusion catheter was used. Coefficient of variation (CV, a mathematical expression of the degree or magnitude of deviation of a set of data points from the mean) was developed in this study as an index of anal canal manometric asymmetry. RESULTS: At 1 cm from the anal verge, mean CV was 9.3 and 8.7 percent in asymptomatic control males and females, respectively. During a maximum voluntary squeeze effort, mean CV in control males was 9.3 percent and was not significantly different (P = 0.28) from that in control females (7.8 percent). In 14 consecutive female patients with fecal incontinence, mean CV at rest (1 cm from the anal verge) was 21 percent and was significantly higher (P < 0.01) than in control females. Similarly, during a maximum voluntary squeeze effort, mean CV in patients with fecal incontinence was 20.5 percent and was significantly higher (P < 0.01) than in the female control group (7.8 percent). CONCLUSION: It is concluded that CV, a method of expressing anal sphincter manometric asymmetry, is a useful manometric parameter in the assessment of anorectal function.

Adult↗
PubMed1995

Spectrum and epidemiology of intestinal failure.

Although there is common agreement about the corecases in which there is no alternative to HPN, cultural and economic differences lead to major variations in the types of disease treated, the ages of patients treated, the duration of and prevalence of treatment. It is unlikely that there will be agreement between countries on the extent to which artificial nutritional support will be used.

Journal Article↗
PubMed1995

Health promotion and the use of Gpass in Scotland.

OBJECTIVE: To identify how computerised practices using Gpass software (General Practice Administration System for Scotland), currently implement the new health promotion regulations. DESIGN: Postal questionnaire to all Gpass practices in Scotland. Data were gathered on types and methods of recording health promotion data, Read code selection, health education given and intended methods of data analysis. Questionnaire results were compared with data from an Electronic Questionnaire analysing actual data recorded on practice computers. RESULTS: Overall response rate: 64.6%, 94.8% of the responding practices have been approved for health promotion band three. Most practices (94.5%) use their computer for data collection, 63.6% of practices use a manual data capture form and 28.8% use computer data capture methods. Methods of collecting patient data and selection of Read codes for computer data entry are variable. Most practices use one method of data collection; a significant minority use multiple methods or more than one Read code to record the same item. The recording of health promotion on computer has increased greatly since the introduction of the new regulations: the current levels of recording are alcohol history (26.3%), blood pressure reading (57.6%), smoking (35.4%), exercise (7.1%), weight (21.4%) and height (16.4%). Most practices (94.3%) intend using Gpass for data analysis. CONCLUSION: Methods of collecting and recording health promotion data differ greatly between practices, with variable standardisation of health promotion codes and differing use of appropriate elements of the Gpass software.

Adult↗
PubMed1995

Transients of fluorescence polarization in skeletal muscle fibers labeled with rhodamine on the regulatory light chain.

Structural changes of the myosin heads were correlated with mechanical events in the cross-bridge cycle by measuring fluorescence polarization signals at high time resolution from rhodamine probes bound to myosin regulatory light chains in skeletal muscle fibers. Motions of the cross-bridges were partially synchronized either by applying quick length changes to the fibers during active contractions or by activating the fibers from rigor by photolysis of caged ATP in the presence of Ca2+. With fibers in rigor, the fluorescence polarization values indicate that the probe dipoles are quite well ordered and are directed away from the muscle fiber axis. After photorelease of ATP from caged ATP, changes in polarization signals are consistent with broadening of the distribution of probe orientations. The signal deflections occur when ATP binds to actomyosin or when the cross-bridges detach, but the orientational distribution changes surprisingly little during active force development. In contrast, when staircases of quick releases are applied to labeled fibers during active contractions, the fluorescence polarization signals suggest a concerted rotation of the probes. The results indicate that the light chain region of myosin tilts during the quick release and/or during the tension recovery phase within the next few ms.

Adenosine Triphosphate↗
PubMed1995

Changes in the x-ray diffraction pattern from single, intact muscle fibers produced by rapid shortening and stretch.

Changes in the x-ray diffraction patterns produced by 100-microseconds-length steps imposed during tetanic stimulation were recorded from single intact fibers of frog tibialis anterior muscle. For shortening steps, a staircase length change was applied, with a 20-ms interval between steps. For stretches, each 20-ms cycle started with a stretch, followed after 4 ms by shortening to the original length. Each shortening step in the staircase and each stretch in the stretch/shortening protocol produced a response similar to that of a single step from the isometric steady state. The intensity of the 14.5-nm x-ray reflection arising from the axial repeat of the myosin heads along their filaments decreased after both shortening and stretch; this decrease was not accompanied by broadening along or across the meridian. The relationship between the intensity after the length step and step amplitude was approximately linear for both stretches and shortening steps, extrapolating to zero intensity for 11-nm stretches and 13-nm shortening steps, but there was no significant intensity change for the first approximately 2 nm of shortening. These results are broadly consistent with conventional models of muscle contraction in which myosin heads move through about 10 nm during the working stroke in the shortening direction, but an additional distortion of the myosin heads may be produced by a stretch.

Animals↗
PubMed1994

Which nutritional measurements assess protein-energy nutritional status in patients receiving home parenteral nutrition?

Weight, midarm circumference, triceps skinfold thickness, arm muscle circumference, albumin, prealbumin, transferrin and total lymphocyte count were measured at each outpatient visit in patients reveiving home parenteral nutrition from September 1987 to November 1991. Each nutritional variable was analysed for individuals and for the whole group. Group data were expressed using the actual values obtained and successive differences (the change between clinic attendances). Nutritional variables were evaluated using a correlation matrix. Identical analysis of individual and group data demonstrates that laboratory investigations are of little value in the assessment of nutritional status in patients receiving home parenteral nutrition. Anthropometry detected changes in body weight secondary to changes in muscle and/or fat in 80% of patients. Pooling anthropometric data distors the relationship between variables owing to inter-individual variability when actual values are used. The method of successive differences is the preferred method of analysis for group anthropometric data.

Journal Article↗
PubMed1994

A birefringence study of changes in myosin orientation during relaxation of skinned muscle fibers induced by photolytic ATP release.

The birefringence of isolated skinned fibers from rabbit psoas muscle was measured continuously during relaxation from rigor produced by photolysis of caged ATP at sarcomere length 2.8-2.9 microns, ionic strength 0.1 M, 15 degrees C. Birefringence, the difference in refractive index between light components polarized parallel and perpendicular to the fiber axis, depends on the average degree of alignment of the myosin head domain with the fiber axis. After ATP release birefringence increased by 5.8 +/- 0.7% (mean +/- SE, n = 6) with two temporal components. A small fast component had an amplitude of 0.9 +/- 0.2% and rate constant of 63 s-1. By the completion of this component, the instantaneous stiffness had decreased to about half the rigor value, and the force response to a step stretch showed a rapid (approximately 1000 s-1) recovery phase. Subsequently a large slow birefringence component with rate constant 5.1 s-1 accompanied isometric force relaxation. Inorganic phosphate (10 mM) did not affect the fast birefringence component but accelerated the slow component and force relaxation. The fast birefringence component was probably caused by formation of myosin.ATP or myosin.ADP.Pi states that are weakly bound to actin. The average myosin head orientation at the end of this component is slightly more parallel to the fiber axis than in rigor.

Adenosine Triphosphate↗