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Biomedical subjects

J Stillman

Publications and source records attributed to J Stillman.

6 recordsLinked to original sources

Fiber-type differences in muscle mitochondrial profiles.

Although striated muscles differ in mitochondrial content, the extent of fiber-type specific mitochondrial specializations is not well known. To address this issue, we compared mitochondrial structural and functional properties in red muscle (RM), white muscle (WM), and cardiac muscle of rainbow trout. Overall preservation of the basic relationships between oxidative phosphorylation complexes among fiber types was confirmed by kinetic analyses, immunoblotting of native holoproteins, and spectroscopic measurements of cytochrome content. Fiber-type differences in mitochondrial properties were apparent when parameters were expressed per milligram mitochondrial protein. However, the differences diminished when expressed relative to cytochrome oxidase (COX), possibly a more meaningful denominator than mitochondrial protein. Expressed relative to COX, there were no differences in oxidative phosphorylation enzyme activities, pyruvate-based respiratory rates, H2O2 production, or state 4 proton leak respiration. These data suggest most mitochondrial qualitative properties are conserved across fiber types. However, there remained modest differences ( approximately 50%) in stoichiometries of selected enzymes of the Krebs cycle, beta-oxidation, and antioxidant enzymes. There were clear differences in membrane fluidity (RM > cardiac, WM) and proton conductance (H+/min/mV/U COX: WM > RM > cardiac). The pronounced differences in mitochondrial content between fiber types could be attributed to a combination of differences in myonuclear domain and modest effects on the expression of nuclear- and mitochondrially encoded respiratory genes. Collectively, these studies suggest constitutive pathways that transcend fiber types are primarily responsible for determining most quantitative and qualitative properties of mitochondria.

Adenosine Triphosphatases↗

Glucose-6-phosphatase flux in vitro is increased in type 2 diabetes.

Despite the effects of hyperinsulinemia and hyperglycemia, 2 factors known to inhibit endogenous glucose production (EGP) in nondiabetic subjects, increased EGP is a consistent feature of type 2 diabetes. Recent studies have suggested that increased glucose-6-phosphatase (G6Pase) and/or decreased glucokinase (GK) may explain the increase in EGP. However, no studies to date have clearly established this relationship in type 2 diabetes. The present studies were designed to determine rates of EGP and the activities of G6Pase and GK in obese patients scheduled for gastric bypass surgery. The study group consisted of 14 obese nondiabetic subjects and 13 patients with type 2 diabetes (BMI 53.7 +/- 2.4 vs. 50.1 +/- 1.6 kg/m2). Rates of EGP were determined after an overnight fast with a 4-h infusion of [6,6]-D-glucose, and they were significantly higher in the type 2 diabetic patients (85.9 +/- 10.0 vs. 137.8 +/- 14.4 mg x m(-2) x min(-1), P < 0.001) despite greater plasma glucose (5.1 +/- 0.1 vs. 12.0 +/- 1.1 mmol/l) and similar insulin concentrations (130.8 +/- 19.8 vs. 112.8 +/- 16.2 pmol/l, NS). Moreover, resistance to insulin-induced suppression of EGP was observed in the patients with type 2 diabetes when insulin concentrations were increased from approximately 120 to 180 pmol/l. Hepatic G6Pase activity determined from freshly isolated microsomes was significantly increased in the type 2 diabetic patients compared with the obese control subjects (0.16 +/- 0.02 vs. 0.09 +/- 0.01 micromol x min(-1) x mg(-1) protein, P < 0.02), whereas levels of GK were decreased (1.20 +/- 0.16 vs. 2.01 +/- 0.01 micromol x min(-1) x mg(-1) protein, P < 0.01). Net flux through G6Pase was significantly increased in type 2 diabetic patients (P < 0.01). We conclude that increased EGP is mediated in part by increased G6Pase flux in type 2 diabetes.

Adult↗

Adaptation to temperature stress and aerial exposure in congeneric species of intertidal porcelain crabs (genus Petrolisthes): correlation of physiology, biochemistry and morphology with vertical distribution

We examined physiological and biochemical responses to temperature and aerial exposure in two species of intertidal porcelain crabs (genus Petrolisthes) that inhabit discrete vertical zones. On the shores of the Northeastern Pacific, P. cinctipes (Randall) occurs under rocks and in mussel beds in the mid to high intertidal zone and P. eriomerus (Stimpson) occurs under rocks in the low intertidal zone and subtidally to 80 m. Because of their different vertical distributions, these two species experience very different levels of abiotic stress. Individuals of P. cinctipes can be emersed during every low tide, but P. eriomerus is only emersed during the lowest spring tides and on most days is not emersed at all. Temperatures measured underneath rocks in the mid intertidal zone were as high as 31 &deg;C, 15 &deg;C higher than maximal temperatures measured under rocks in the low intertidal zone. In air, at 25 &deg;C, large specimens of P. cinctipes were able to maintain a higher respiration rate than similarly sized P. eriomerus. No interspecific differences in the respiratory response to emersion were seen in small specimens. Examination of the response of heart rate to temperature revealed that P. cinctipes has a 5 &deg;C higher Arrhenius break temperature (ABT, the temperature at which there is a discontinuity in the slope of an Arrhenius plot) than its congener (31.5 &deg;C versus 26.6 &deg;C). The heart rate of P. cinctipes recovered fully after exposure to cold (1.5 &deg;C), but the heart rate of P. eriomerus did not recover after exposure to 2 &deg;C or cooler. The ABT of heart rate in P. cinctipes was very close to maximal microhabitat temperatures; thus, individuals of this species may be living at or near their thermal tolerance limits. P. cinctipes were able to maintain aerobic metabolism during emersion, whereas P. eriomerus shifted to anaerobic metabolism. A pronounced accumulation of whole-body lactate was found in specimens of P. eriomerus incubated in air at 25 &deg;C over a 5 h period, but not in P. cinctipes similarly treated. P. cinctipes possesses a membranous structure on the ventral merus of each walking leg, but this structure is not found in P. eriomerus. To test the function of the leg membrane, we measured the aerial respiration rates and the lactate accumulation of P. cinctipes with their leg membranes obscured. These individuals had significantly lower aerial respiration rates at 30 &deg;C than control crabs. Crabs with leg membranes obscured also accumulated a considerable amount of lactate during a 5 h period of emersion at 28 &deg;C, but control crabs showed no accumulation under the same conditions. These data suggest that the leg membrane functions as a respiratory structure. The results of this study illustrate that a suite of morphological, physiological and biochemical features allows P. cinctipes to live higher in the intertidal region than P. eriomerus.

Journal Article↗

Role of hepatocyte plasma membrane in insulin degradation.

An important role of the cell membrane in insulin degradation by cultured rat hepatocytes is supported by studies using the surface-active antibiotic bacitracin. Bacitracin inhibited degradation of cell-associated insulin (both randomly and A14 labeled) by 80-90% at 15 degrees C and by 60% at 37 degrees C. At 37 degrees C, inhibition of degradation was observed only with bacitracin present during dissociation and was accompanied by a compensatory increase in release of trichloroacetic acid (TCA)-precipitable insulin. This profile suggests inhibition of insulin degradation on the membrane after either primary binding or diacytosis (endocytosis-reverse endocytosis). In contrast, at 15 degrees C, bacitracin's inhibitory effect was greater with the antibiotic present during association and was not accompanied by a compensatory increase in TCA-precipitable insulin. This profile was compatible with inhibition of partial cleavage of insulin on the membrane. Internalization and degradation through chloroquine-sensitive pathways may be required to complete degradation at this temperature because chloroquine exhibited an inhibitory effect on insulin degradation equally potent to that of bacitracin at 15 degrees C (no effect at 37 degrees C).

Animals↗

Telemedicine and rural health care applications.

Telemedicine has the potential to help facilitate the delivery of health services to rural areas. In the right circumstances, telemedicine may also be useful for the delivery of education and teaching programmes and the facilitation of administrative meetings. In this paper reference is made to a variety of telemedicine applications in Australia and other countries including telepaediatrics, home telehealth, critical care telemedicine for new born babies, telemedicine in developing countries, health screening via e-mail, and teleradiology. These applications represent some of the broad range of telemedicine applications possible. An overriding imperative is to focus on the clinical problem first with careful consideration given to the significant organisational changes which are associated with the introduction of a new service or alternative method of service delivery. For telemedicine to be effective it is also important that all sites involved are adequately resourced in terms of staff, equipment, telecommunications, technical support and training. In addition, there are a number of logistical factors which are important when considering the development of a telemedicine service including site selection, clinician empowerment, telemedicine management, technological requirements, user training, telemedicine evaluation, and information sharing through publication.

Australia↗