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R M Lynch

Publications and source records attributed to R M Lynch.

44 records · Page 3Linked to original sources

Energy metabolism and transduction in smooth muscle.

Early investigations into the nature of the coupling between energy transduction and metabolism in smooth muscle, particularly from the laboratories of Bülbring and Lundholm, suggested that specific metabolic pathways could independently supply energy for ion transport and actin-myosin interactions. Subsequent work has solidified the concept that oxidative phosphorylation is specifically coupled to tension generation and maintenance, whereas, aerobic glycolysis is not only a vital characteristic of smooth muscle metabolism, but also is likely to be independently coupled to Na-K transport at the plasmalemma. The independence of oxidative and glycolytic metabolism is reflected as a compartmentation of carbohydrate metabolism in the porcine carotid artery. The coupling of these independent metabolic pathways with specific energy utilizing processes, indicates a means by which energy production and transduction can be closely and efficiently regulated. The coupling of glycogenolysis to mitochondrial respiration may have evolved as a direct response to the energetic needs of VSM. That is, the large glycogenolytic response in the initial minutes of stimulation may be necessary to maximize the cellular production of ATP during the presteady state. Likewise, the coupling between aerobic glycolysis and Na-K transport indicates a sensitive and efficient means of coordinating energy metabolism with ion transport at the membrane level. Additionally, the regulation of substrate supply, i.e. glucose transport, also may be closely coordinated with changes in ion transport. One may speculate that alterations in the microenvironment of each compartment can independently regulate intermediary metabolism and therefore allow the cell to quickly and efficiently respond to localized stimuli. Thus, stimulation of Na-K transport could effectively regulate energy production at the membrane level without mobilizing or competing with the energy transduction of other cellular processes. This compartmentation of energy utilization may be highly advantageous, since oxidative metabolism is closely coordinated with mechanical activity and therefore regulation of blood flow. Future investigations will attempt to elucidate which intracellular signals which are responsible for the regulation of these functionally independent compartments of energy metabolism and transduction in VSM. In more general terms, our findings provide a basis from which future questions concerning the regulation of cellular metabolism must be directed. The cellular cytoplasm can no longer be envisioned as a homogeneous compartment, but rather a complex array of functional subcompartments which may be individual

Animals↗

Vascular smooth muscle energetics.

ATP utilization (delta approximately P) during an isometric contraction has been studied in terms of both measurements of oxygen consumption and lactate production as well as of the tissue nucleotide and metabolite levels. The contribution of breakdown of preformed ATP and phosphocreatine (PCr) pools to delta approximately P during contraction is minor compared to that made by metabolic synthesis of ATP. For tonic vascular smooth muscle (VSM), in fact, no change in ATP or PCr from resting levels can be measured. In contrast to amphibian skeletal muscle, a P:O of 3 can be demonstrated in VSM. In both tonic and phasic VASM, delta approximately P is biphasic with contraction duration, attaining a maximal value before that of isometric force and declining to a steady-state value approximately 60% of the maximal suprabasal rate during the maintenance of constant isometric force. The steady-state rate of ATP utilization per unit force maintained increases with extracellular Ca2+. Both the pre-steady-state temporal dependence and the steady-state dependence on Ca2+ are consistent with the hypothesis that myosin phosphorylation modulates the cross-bridge cycle rates. VSM metabolism, when viewed in terms of ATP synthesis, is primarily oxidative. However, even under fully oxygenated conditions, lactate is the major end product of glucose catabolism. Recent work has shown that aerobic lactate production is specifically coupled to Na-K transport in many, but not all, vascular tissues. Oxidative metabolism, on the other hand, is strongly related to active isometric force. The biochemical basis of this functional compartmentation was investigated at the level of substrate specificity.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerobiosis↗

Glucose uptake in porcine carotid artery: relation to alterations in active Na+-K+ transport.

In vascular smooth muscle (VSM), aerobic lactate production can account for as much as 30% of the basal rate of ATP production. Generally, glucose transport is thought to be the rate-limiting step for glycolysis in unstimulated VSM. In this work we provide evidence that the intracellular concentration of glucose is negligible in porcine carotid artery, indicating that glucose transport is rate limiting for its utilization. Since aerobic glycolysis appears to be coupled to active Na+-K+ transport in this tissue, we examined the effects of altering ion transport on glucose transport. Glucose uptake and 3-O-methyl-D-glucose transport were accelerated, though intracellular glucose remained negligible in artery rings that were incubated with 80 mM KCl, which is known to stimulate active Na+-K+ transport, as well as aerobic glycolysis and mechanical activity. On the other hand, inhibitors of active Na+-K+ transport (ouabain, Na+-free media), which also elicit mechanical activity, had little effect on sugar transport but significantly inhibited aerobic glycolysis and caused an intracellular accumulation of glucose. Our results indicate the following: 1) that glucose transport is regulated in VSM; 2) that the intracellular concentration of Ca2+ does not appear to regulate sugar transport, since changes in glucose and 3-O-methyl-D-glucose transport are not always seen in association with increased mechanical activity, and 3) that the decrease in aerobic glycolysis associated with the inhibition of active Na+-K+ transport is not due to a decrease in glucose transport but rather to an inhibition of glucose utilization.

3-O-Methylglucose↗

Compartmentation of glycolytic and glycogenolytic metabolism in vascular smooth muscle.

Vascular smooth muscle is characterized by a high rate of aerobic lactate production, which may be altered independently of oxidative phosphorylation. This finding suggested a cytoplasmic compartmentation of metabolism. Exogenous glucose was found to be the sole precursor of aerobic glycolysis under unstimulated conditions. Although tissue depolarization with high K+ resulted in a substantial reduction of endogenous glycogen, exogenous glucose remained the sole precursor of aerobic lactate production. These data showed unequivocally that carbohydrate metabolism is compartmentalized in vascular smooth muscle.

Animals↗

Neuroimaging in neuro-ophthalmology.

The neuroradiologist and the clinician are partners in the search for pathology; the clinician must help the radiologist tailor the study by indicating where pathology is likely to be. The orbit, the sellar and parasellar regions, and new imaging modalities and interventional techniques are discussed in this light.

Brain Neoplasms↗

Short-term efficacy of back injury intervention project for patient care providers at one hospital.

A one-year Back Injury Prevention Program was initiated at a 440-bed acute care hospital in 1996 in response to concerns over high incidence and severity of back injuries among nursing staff and others. The program included an ergonomic evaluation of patient handling, pilot testing and purchase of new equipment, a train-the-trainer program, and training of 374 nurses and other patient handling staff (approximately one-half of the nursing staff). An impact evaluation, measured by comparing self-reported knowledge, work practices, and back pain among a subset of trainees and controls revealed an increase in knowledge of risk factors, a marginal increase in the use of mechanical devices to transfer patients, and a significant decrease in repositioning of patients in bed among trained versus control subjects (p = .017). Over the course of the program, the number of back injuries was 30% below the average of the prior 3 years, with the number of reported injuries in the final quarter (immediately following the training program) approximately one-seventh of the three prior quarters. It is concluded that back injury training may increase knowledge of risk factors and controls and may impact behaviors over which individuals have control (e.g., how often they move patients). However, training effectiveness is limited when engineering controls such as patient transfer devices are unavailable.

Back Injuries↗

Building-related illness and employee lost time following application of hot asphalt roof: a call for prevention.

Industrial hygiene sampling within an office building during and following a roof renovation revealed low-level exposure to high-boiling organic compounds, associated with complaints of eye and upper respiratory tract irritation among building occupants. Health complaints continued substantially beyond the time frame of the renovation completion, despite a lack of objective industrial hygiene findings for volatile organic compounds (VOCs) and microbiological contamination, and a lack of consistent medical findings among employees evaluated by an occupational physician. An analysis of employee attendance records suggests lost attendance and reduced productivity costs. Preventive strategies include proper planning and scheduling of building renovations to prevent employee exposure to asphalt roof emissions.

Adult↗