Note: Infrared laser diagnostics for deuterium gas puff Z pinches.

Deuterium gas puff Z pinches have been used for generation of strong neutron fluxes on the MA class pulse power machines. Due to the low electron density of deuterium Z-pinch plasma, regular laser diagnostics in the visible range cannot be used for observation and study of the pinch. Laser probing at the wavelength of 1064 nm was used for visualization of deuterium plasma. Infrared schlieren and interferometry diagnostics showed the deuterium gas puff plasma dynamics, instabilities, and allowed for the reconstruction of the profile of the plasma density.

Inhibition of mammalian mitochondrial protein synthesis by oxazolidinones.

The effects of a variety of oxazolidinones, with different antibacterial potencies, including linezolid, on mitochondrial protein synthesis were determined in intact mitochondria isolated from rat heart and liver and rabbit heart and bone marrow. The results demonstrate that a general feature of the oxazolidinone class of antibiotics is the inhibition of mammalian mitochondrial protein synthesis. Inhibition was similar in mitochondria from all tissues studied. Further, oxazolidinones that were very potent as antibiotics were uniformly potent in inhibiting mitochondrial protein synthesis. These results were compared to the inhibitory profiles of other antibiotics that function by inhibiting bacterial protein synthesis. Of these, chloramphenicol and tetracycline were significant inhibitors of mammalian mitochondrial protein synthesis while the macrolides, lincosamides, and aminoglycosides were not. Development of future antibiotics from the oxazolidinone class will have to evaluate potential mitochondrial toxicity.

FINDMOL: automated identification of macromolecules in electron-density maps.

Automating the determination of novel macromolecular structures via X-ray crystallographic methods involves building a model into an electron-density map. Unfortunately, the conventional crystallographic asymmetric unit volumes are usually not well matched to the biological molecular units. In most cases, the facets of the asymmetric unit cut the molecules into a number of disconnected fragments, rendering interpretation by the crystallographer significantly more difficult. The FINDMOL algorithm is designed to quickly parse the arrangement of trace points (pseudo-atoms) derived from a skeletonized electron-density map without requiring higher level prior information such as sequence information or number of molecules in the asymmetric unit. The algorithm was tested with a variety of density-modified maps computed with medium- to low-resolution data. Typically, the resulting volume resembles the biological unit. In the remaining cases the number of disconnected fragments is very small. In all examples, secondary-structural elements such as alpha-helices or beta-sheets are easily identifiable in the defragmented arrangement. FINDMOL can greatly assist a crystallographer during manual model building or in cases where automatic model building can only build partial models owing to limitations of the data such as low resolution and/or poor phases.

Guanine nucleotide transport by atractyloside-sensitive and -insensitive carriers in isolated heart mitochondria.

In previous work (McKee EE, Bentley AT, Smith RM Jr, and Ciaccio CE, Biochem Biophys Res Commun 257: 466-472, 1999), the transport of guanine nucleotides into the matrix of intact isolated heart mitochondria was demonstrated. In this study, the time course and mechanisms of guanine nucleotide transport are characterized. Two distinct mechanisms of transport were found to be capable of moving guanine nucleotides across the inner membrane. The first carrier was saturable, displayed temperature dependence, preferred GDP to GTP, and did not transport GMP or IMP. When incubated in the absence of exogenous ATP, this carrier had a V(max) of 946 +/- 53 pmol. mg(-1). min(-1) with a K(m) of 2.9 +/- 0.3 mM for GDP. However, transport of GTP and GDP on this carrier was completely inhibited by physiological concentrations of ATP, suggesting that this carrier was not involved with guanine nucleotide transport in vivo. Because transport on this carrier was also inhibited by atractyloside, this carrier was consistent with the well-characterized ATP/ADP translocase. The second mechanism of guanine nucleotide uptake was insensitive to atractyloside, displayed temperature dependence, and was capable of transporting GMP, GDP, and GTP at approximately equal rates but did not transport IMP, guanine, or guanosine. GTP transport via this mechanism was slow, with a V(max) of 48.7 +/- 1.4 pmol. mg(-1). min(-1) and a K(m) = 4.4 +/- 0.4 mM. However, because the requirement for guanine nucleotide transport is low in nondividing tissues such as the heart, this transport process is nevertheless sufficient to account for the matrix uptake of guanine nucleotides and may represent the physiological mechanism of transport.

Aerobic training in a patient with nonsevere aplastic anemia: a case report.

This case report examined whether a 26-year-old man with a 5-year history of nonsevere aplastic anemia could perform aerobic training and whether exercise was beneficial. Testing was performed at baseline and at 8 and 16 weeks and included complete blood tests, graded exercise tests with breath-by-breath gas analyses, and health status assessment with the Medical Outcomes Survey SF-12 health survey. Training consisted of treadmill walking for 25 minutes, 3 days a week for 16 weeks, at 75% of maximal heart rate. The patient successfully completed 16 weeks of training and had no adverse effects from testing or training. Training did not produce changes in disease-related measures (hematologic values) or impairment measures (cardiopulmonary measures of fitness). The mental component of the SF-12 improved from below 2 standard deviations from the population mean to within 1 standard deviation of the population mean. The benefits of aerobic training for this person with aplastic anemia were that he showed that he could participate in aerobic-type activities and that training appeared to improve his mental health.

Optimism as an indicator of psychological health: using psychological assessment wisely.

Healthy aspects of psychological functioning are often overlooked in traditional psychological assessment. When this happens, the client may become discouraged with his or her testing results, or perhaps worse, may feel that the assessor was not interested in obtaining a complete picture of who he or she is. Assessing healthy aspects of psychological functioning can be problematic, however; adding new instruments that only speak to one aspect of psychological functioning is not practical. A system is proposed in which one aspect of healthy psychological functioning--optimism--can be assessed using a standard projective test. Use of this scale can aid the assessor in conceptualizing the client's functioning and can also be a helpful tool to draw on in the course of treatment.

Origin of guanine nucleotides in isolated heart mitochondria.

Presence of guanine nucleotide within the matrix of mitochondria is uncontested; the mechanism by which GTP takes up residence in the matrix is unknown. In this report, we demonstrate for the first time that direct transport of guanine nucleotide across the inner membrane of heart mitochondria is possible. Transport of guanine nucleotides from the medium to the matrix was suggested by inhibition of translation in isolated rat heart mitochondria when GTP-gamma-S was added to the medium. This result suggested that GTP was one source of matrix GTP. Other sources were investigated by measuring matrix uptake and conversion to GTP of several purines, purine nucleosides, and purine nucleotides. Results demonstrated that [14C]-guanine and [3H]-guanosine were not taken up by isolated mitochondria and were not converted to any other compound. While [14C]-ATP and [3H]-AMP were taken up readily into the matrix, radioactivity was never associated with a guanine compound. [3H]-IMP was not taken up into the matrix and was never converted to another compound. Our data showed that label added as [3H]-GTP, [3H]-GDP, or [3H]-GMP was readily taken up and concentrated in the matrix of isolated mitochondria.

Malignant rhabdoid tumor of the duodenum.

A polypoid malignant rhabdoid tumor of the duodenum is presented. The pattern of metastatic spread in this 58-year-old man included multiple duodenal and small intestinal transmural tumor implants and a large peribronchial lymph node causing superior vena cava syndrome. Microscopically, the tumor was composed of a diffuse population of rhabdoid cells characterized by homogeneous globular cytoplasmic inclusions that tended to indent or displace eccentric, vesicular nuclei with nucleoli. No glandular features were noted. Immunohistochemical and ultrastructural evaluation revealed that these inclusions contained vimentin, an intermediate filament of the mesenchymal cytoskeleton. Phenotypic features of a rhabdoid tumor have been reported in 10 poorly differentiated malignancies of the gastrointestinal tract. This is the first case report of a malignant rhabdoid tumor of the small intestine. Regardless of the site of the lesion, tumors showing these features are generally associated with a poor prognosis.

Telemetry system for monitoring anterior cruciate ligament graft forces in vivo.

Quantifying changes in the tension of an anterior cruciate ligament (ACL) graft in vivo during rehabilitative exercises is useful for developing the optimum rehabilitation for patients who have had reconstructive surgery. The purpose of the work reported is to design, build and test a telemetry system that can measure the in vivo ACL graft tension post-operatively. A commercially available fixation device is modified to sense the graft tension, house electronic components, transmit an output signal and pass the power generating signal. A transcutaneous inductive link is used to power the implanted telemetry electronics. The current difference technique is used to measure changes in two resistance strain gauges that monitor shear strain developed on the femoral fixation device by the ACL graft. This current regulates a frequency-modulated output signal that is transmitted using a new technique. Harnessing the ionic and volume conduction properties of the body fluids, the new technique involves injecting current subcutaneously into the tissue and then sensing the potential developed on the skin by surface electrodes. The waveform shape, amount of charge injected, charge density and current density are regulated to avoid tissue damage, pain and unwanted muscular stimulation. A signal conditioning board detects and converts the output to an analogue voltage for collection by a computer data-acquisition system. A performance evaluation demonstrates that the telemetry system either meets or exceeds all of the criteria necessary for the application.

A cardiovascular health needs assessment of university students living in residence.

The purpose of this study was to determine the cardiovascular health needs of university students living in residence. A survey was administered to students living in residence at a university in Nova Scotia, Canada to identify eating patterns, physical activity, smoking behaviours and perceived stress. Data were analyzed using descriptive statistics and chi-square tests of association. Qualitative data were collected using focus group interviews. Results showed that fewer than half of the students participated in exercise three or more times per week, and 82% are less than the recommended amount of fruits and vegetables. As perceived knowledge of CVD increased so did level of physical activity and consumption of fruits and vegetables. Fifty-six percent of students rated their stress as high or very high; exams and course assignments are a major cause of this stress. Fifteen percent of the university students surveyed were daily smokers. Barriers to a healthy lifestyle include time constraints and limited food choices in the residence cafeteria.

A new technique for transmission of signals from implantable transducers.

To reduce space requirements for implant electronics in in vivo telemetry applications, the purpose of this project was to develop and test a new data transmission method that utilizes the ionic properties of bodily fluids as the transmission medium. Motivated by an interest in using the new method to transmit information from a sensor which measures tension in anterior cruciate ligament (ACL) grafts, a sine wave was injected into a cadaver leg using platinum electrodes implanted into the lateral femoral epicondyle. The signal was detected by electromyogram (EMG) surface electrodes. The effect of transmission frequency, the current injected, interelectrode separation, distance of the electrodes from the joint line, and the surface of electrode placement on the signal attenuation was studied. The logarithmic relation between attenuation and frequency was constant from 2 kHz until 10 kHz. For frequencies above 10 kHz, the attenuation increased linearly at the rate of 1 dB/octave. Attenuation was inversely sensitive to both current and interelectrode separation with larger separations and currents giving less attenuation. Attenuation was significantly less for the lateral thigh surface than for the anterior surface and increased with increasing distance from the joint line for both surfaces. For the application of interest here, suitable values of transmission variables to avoid the possible negative consequences of injecting current into living tissue are a current of 3 mA injected at a frequency of 37 kHz. The values of reception variables for minimum attenuation are wide interelectrode separation (5 cm) with the electrodes placed 5 cm proximal of the joint line on the lateral surface of the thigh. With the exception of the surface which is application dependent, these values of the reception variables should also be appropriate for other applications.

Effect of three teaching methods on a nursing staff's knowledge of medication error risk reduction strategies.

The authors' purpose in this study was to (1) compare the effects of three teaching methods on registered nurses' and licensed practical nurses' knowledge of medication error risk reduction strategies, and (2) to compare registered nurses' and licensed practical nurses' knowledge of medication error risk reduction strategies using a pretest/posttest design. Registered nurses (n = 129) and licensed practical nurses (n = 21) employed by two hospitals constituted the study sample. Subjects were assigned alternately to three intervention groups: videotape (n = 50); instructional booklet (n = 50); and lecture (n = 50). A 38-item test, including true-false, multiple choice, matching items and dosage calculation problems, was administered to subjects in each group before and after the teaching intervention. On the basis of the results, there was no statistically significant difference in total knowledge scores for the three intervention groups (F = 2.07, P = 0.130). Staff development instructors should consider the advantages of a videotape and instructional booklet over the time-intensive lecture strategy.

Mitochondrial gene expression in Saccharomyces cerevisiae. IV. Effects of yeast cytosol on mitochondrial protein synthesis, degradation, and respiration.

It has been known for some time that the addition of a crude yeast cytosolic fraction to isolated mitochondria stimulates the rate of amino acid incorporation into protein in the isolated organelles. However, the mechanism and importance of this phenomenon relative to mitochondrial function has not been established. While it has been assumed that this effect is at the level of translation, the recognition that newly synthesized mitochondrial translation products are rapidly degraded in isolated yeast mitochondria raises the possibility that cytosol affects amino acid incorporation by inhibiting proteolysis. Using pulse-chase experiments we demonstrate that the rate constants of degradation of the nascent products are not affected by yeast cytosol. Further, not only is proteolysis not inhibited by cytosol, but the loss of label caused by proteolysis is actually increased. This increase is directly related to an increase in the size of the nascent product pool which increases simply as a consequence of increasing the rate of translation. By utilizing an approach in which the loss of label due to proteolysis is minimized, the true stimulatory activity of the cytosolic fraction on synthesis was determined (2.1-fold vs. 1.3-fold by the previous method). Pulse-chase experiments in the presence of pactamycin, an initiation inhibitor, demonstrate that yeast cytosol causes an initial increase in the rate of translational initiation without increasing the rate of elongation. However, at later intervals the yeast cytosol acts primarily to maintain the rate of elongation which falls steadily in the controls. Finally, the presence of yeast cytosol dramatically increases the length of incubation time in which the mitochondrial preparation consumes oxygen and maintains coupled respiration, parameters that fall rapidly in the controls. Thus, a yeast cytosolic fraction may function to promote the stability of the mitochondrial preparation, which in turn may account for the increase in rates of translation, particularly with regard to maintaining rates of elongation.

A modified newborn intensive care unit environment may shorten hospital stay.

Premature infants with birth weights from 1121 to 2000 gm were assigned randomly to two groups. Experimental group infants were placed on a microprocessor-controlled cradle that provided levels of motion and sound analogous to those of the third-trimester intrauterine environment. Periods of motion totaling 50% of the time were randomized on and off; motion speed was reduced 35% during a 12-hour night period. A uterine souffle sound was generated continuously but varied in pulse rate and volume with the motion and speed of the bed. Experimental group infants (n = 20) were placed on the cradle under a radiant warmer as soon as their condition was stable clinically. Control group infants (n = 18) were usually placed initially under a radiant warmer and transferred to an incubator when their condition was stable. Otherwise, both groups received standard newborn intensive care unit care. The mean length of hospital stay was significantly shorter for experimental group infants than for control group infants after controlling for gestational age and weight on entry to the study. Experimental group infants began nippling earlier and stopped requiring gavage feedings sooner. Experimental group infants had a decreased incidence of apnea. Blinded Brazelton Neonatal Behavioral Assessment Scale scores for the Orientation and Range of State cluster scales were significantly better for experimental group infants. A retrospective contrast group of preterm infants who met study criteria had an average length of stay similar to that of the control group infants. These data support the hypothesis that appropriate levels and kinds of stimulation may facilitate the maturation of preterm infants.

Mitochondrial gene expression in Saccharomyces cerevisiae. Proteolysis of nascent chains in isolated yeast mitochondria optimized for protein synthesis.

We demonstrate here that mitochondrial translation products synthesized by isolated yeast mitochondria are subject to rapid proteolysis. The loss of label from mitochondrial peptides synthesized in vitro comes from two distinct pools of peptides: one that is rapidly degraded (t1/2 of minutes) and one that is much more resistant to proteolysis (t1/2 of hours). As the length of the incubation period increases, the percentage of labelled peptides in the rapidly-turning-over pool decreases and cannot be detected after 60 min of incubation. This proteolysis is inhibited by chloramphenicol and is dependent on the presence of ATP. The loss of label during the chase occurs from fully completed translation products. The proteolysis observed here markedly affects measurements of rates of mitochondrial protein synthesis in isolated yeast mitochondria. In earlier work, in which proteolysis was not considered, mitochondrial translation was thought to stop after 20-30 min of incubation. In the present study, by taking proteolysis into account, we demonstrate that the rate of translation in isolated mitochondria is actually constant for nearly 60 min and then decreases to near zero by 80 min of incorporation. These findings have allowed us to devise a procedure for measuring the 'true' rate of translation in isolated mitochondria. In addition, they suggest that mitochondrial translation products which normally assemble with nuclear-encoded gene products into multimeric enzyme complexes are unstable without their nuclear-encoded counterparts.

Myosin heavy chain turnover during cardiac mass changes by glucocorticoids.

One aim of this investigation was to determine whether the cardiac enlargement observed with glucocorticoid treatment is temporary or remains a permanent adaptation if steroid treatment is prolonged. A second aim was to study whether myosin heavy chain (MHC) synthesis rates are coordinated with the cardiac mass responses. Female rats received either a vehicle (1% aqueous carboxymethyl cellulose in saline) or hydrocortisone 21-acetate for 1, 3, 7, 11, and 15 days. Peak cardiac enlargement (10-15%) was observed after 7 days of hormone treatment in two separate series of experiments. The enlargement was maintained through 11 days of steroid injections but by 15 days had declined toward control levels. MHC synthesis measurements were performed by constant infusion of [3H]leucine. Leucine specific activities were similar among precursor pools (intracellular, extracellular, and leucyl-tRNA) and did not vary with steroid treatments. Fractional synthesis rates of ventricular MHC (%/day) did not change during the period of increase in ventricular mass but were reduced to 56-59% of controls (-11/19.5) at 7 and 11 days of treatment, when ventricular mass increases were highest. MHC breakdown (%/day) was reduced to approximately 60% (-11.5/18.7) of controls at 7 and 11 days. Changes in total protein synthesis, which was measured in isolated perfused hearts, were similar to the MHC responses and indicated that the alterations in MHC synthesis are synchronized with the hormonal effects on total protein metabolism. These results demonstrate that peak cardiac enlargement is not maintained with long-term glucocorticoid treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin stimulates mitochondrial protein synthesis and respiration in isolated perfused rat heart.

The rates of synthesis of mitochondrial proteins by both the cytoplasmic and mitochondrial protein synthetic systems, as well as parameters of respiration, were measured and compared in mitochondria isolated from fresh, control perfused, and insulin-perfused rat hearts. The respiratory control ratio (RCR) in mitochondria from fresh hearts was 8.1 +/- 0.4 and decreased to 6.0 +/- 0.2 (P less than 0.001 vs. fresh) in mitochondria from control perfused hearts and to 6.7 +/- 0.2 (P less than 0.005 vs. fresh and P less than 0.02 vs. control perfused) for mitochondria from hearts perfused in the presence of insulin. A positive correlation between the RCR and the rate of mitochondrial translation was demonstrated in mitochondria from fresh hearts. In mitochondria isolated from control perfused hearts, the rate of protein synthesis decreased to 84 +/- 3% of the fresh rate after 30 min of perfusion and fell further to 64 +/- 3% after 3 h of perfusion. The inclusion of insulin in the perfusion buffer stimulated mitochondrial protein synthesis 1.2-fold by 1 h (P less than 0.005) and 1.34-fold by 3 h of perfusion (P less than 0.001). The addition of insulin to 1-h control perfused hearts shifted the rate of mitochondrial protein synthesis from the control level to the insulin-perfused level within 30 min of additional perfusion, whereas 1 h was required to shift the RCR values of these mitochondria from control levels to insulin-perfused levels. Thus, whereas RCR was a useful predictor of mitochondrial translation rates, it did not account for the effects of insulin on mitochondrial translation.(ABSTRACT TRUNCATED AT 250 WORDS)

Mitochondrial protein synthesis during thyroxine-induced cardiac hypertrophy.

The goal of this paper was to determine the effects of 3,5,3'-triiodothyronine (T3)-thyroxine-induced cardiac hypertrophy on the rates of synthesis of mitochondrial proteins by both the cytoplasmic and mitochondrial protein synthesis systems and to compare the results with total protein synthesis and cardiac enlargement. Daily injections of T3-thyroxine in the rat resulted in a 25% increase in the growth of the ventricle compared with controls. The cytoplasmic synthesis of both mitochondrial and total proteins as measured in the isolated perfused heart was stimulated by T3-thyroxine injection to a peak of 155 and 146%, respectively, of vehicle-injected controls after 3 days of hormone treatment. This peak was followed by a gradual decline in stimulation in total protein synthesis to 132% of control by 9 days of injection, whereas the decline in stimulation of cytoplasmic synthesis of mitochondrial proteins was significantly steeper, falling to 119% of vehicle control. The rate of protein synthesis within the mitochondrial compartment was also measured during the time course of T3-thyroxine-induced hypertrophy. These rates were measured in an isolated intact heart mitochondrial protein synthesis system described and characterized in the companion papers [E. E. McKee, B. L. Grier, G. S. Thompson, and J. D. McCourt. Am. J. Physiol. 258 (Endocrinol. Metab. 21): E492-E502, 1990; and E. E. McKee, B. L. Grier, G. S. Thompson, A. C. F. Leung, and J. D. McCourt. Am. J. Physiol. 258 (Endocrinol. Metab. 21): E503-E510, 1990]. Rates of mitochondrial protein synthesis were dramatically stimulated by T3-thyroxine injection.(ABSTRACT TRUNCATED AT 250 WORDS)