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Biomedical subjects

S B Leighton

Publications and source records attributed to S B Leighton.

16 recordsLinked to original sources

Down-regulation of nitric oxide production by ibuprofen in human volunteers.

Ibuprofen has been shown in vitro to modulate production of nitric oxide (NO), a mediator of sepsis-induced hypotension. We sought to determine whether ibuprofen alters NO production and, thereby, vascular tone, in normal and endotoxin-challenged volunteers. Techniques for detecting NO were validated in 17 subjects infused with sodium nitroprusside, a NO donor. Then, endotoxin (4 ng/kg) or saline (vehicle alone) was administered in a single-blinded, crossover design to 12 other subjects randomized to receive either ibuprofen (2400 mg p.o.) or a placebo. Endotoxin decreased mean arterial pressure (MAP; P =.002) and increased alveolar NO flow rates (P =.04) and urinary excretion of nitrite and nitrate (P =.07). In both endotoxemic and normal subjects, ibuprofen blunted the small fall in MAP associated with bed rest (P =.005) and decreased alveolar NO flow rates (P =.03) and urinary excretion of nitrite and nitrate (P =.02). However, ibuprofen had no effect on the decrease in MAP caused by endotoxin, although it blocked NO production to the point of disrupting the normal relationship between increases in exhaled NO flow rate and decreases in MAP (P =.002). These are the first in vivo data to demonstrate that ibuprofen down-regulates NO in humans. Ibuprofen impaired the NO response to bed rest, producing a small rise in blood pressure. Although ibuprofen also interfered with the ability of endotoxin to induce NO production, it had no effect on the fall in blood pressure, suggesting that the hemodynamic response to endotoxin is not completely dependent on NO under these conditions.

Adult↗

Gene expression profiling of alveolar rhabdomyosarcoma with cDNA microarrays.

Several forms of human sarcoma, lymphoma, and leukemia are characterized by somatically acquired chromosome translocations that result in fusion genes that encode chimeric transcription factors with oncogenic properties. We have used cDNA microarrays containing 1238 cDNAs to investigate the gene expression profile of a group of seven alveolar rhabdomyosarcoma (ARMS) cell lines characterized by the presence of the PAX3-FKHR fusion gene. Using the method of multidimensional scaling to represent the relationships among the cell lines in two-dimensional Euclidean space, we determined that ARMS cells show a consistent pattern of gene expression, which allows the cells to be clustered together. By searching across the seven ARMS cell lines, we found that 37 of 1238 genes were most consistently expressed in ARMS relative to a reference cell line. Only three of these genes have been previously reported to be expressed in ARMS. Among these 37 were genes related to both primary (PAX3-FKHR) and secondary (CDK4) genetic alterations in ARMS. These results in ARMS demonstrate the potential of cDNA microarray technology to elucidate tumor-specific gene expression profiles in human cancers.

Chromosomes, Human, Pair 13↗

A multimode dynamometer for in vivo MRS studies of human skeletal muscle.

The implementation of muscle ergometry during magnetic resonance spectroscopy and imaging is complicated by the restrictive dimensions of the magnet bore and the presence of a strong static magnetic field. We have developed a dynamometer that is compatible with these constraints. This device can provide resistance to voluntary muscle contraction during isometric, isokinetic concentric, and isokinetic eccentric muscle contractions. While controlling muscle contraction speed, the dynamometer simultaneously records muscle torque production at a 10-Hz sampling frequency to allow assessment of compliance and retrospective normalization of power output for the mass of active muscle. All parameters relevant to muscle contraction are selectable, including percentage of maximal voluntary contraction, velocity of muscle contraction, duty cycle, and range of motion for the contraction. This paper provides examples of 31P-magnetic resonance spectroscopic measurements during isokinetic concentric contractions of the ankle dorsiflexors, isokinetic eccentric contractions of the soleus, and isometric contractions of the soleus. Operation of the dynamometer has no adverse effects on the integrity of the 31P-magnetic resonance spectra at 4 T, permitting temporal resolution of the phosphocreatine resynthesis rate of approximately 1 spectrum/s. The unique capabilities of this dynamometer will facilitate studies into the metabolic response of working muscle in healthy and diseased populations.

Adult↗

Cerebrospinal fluid pressure as a function of body position in dogs.

Cerebrospinal fluid (CSF) pressure has been measured as a function of body position in dogs under pentobarbital anaesthesia. CSF pressure was higher than superior sagittal sinus pressure by an almost constant 6 cm of water, regardless of position, if 30 min were allowed for the system to reach equilibrium. The sinus pressure was found to depend on simple hydrostatic theory when the sinus was at or below the level of the heart. When the sinus was above the heart, the collapsing nature of the jugular veins prevented the sinus pressure from dropping as low as a simple hydrostatic theory would predict.

Animals↗

Hepatic parenchymal suction dissector.

A new instrument for hepatic parenchymal dissection has been developed. It is used to suction dissect tissue from around vessels and ducts to minimize blood loss during hepatic operations. The instrument is inexpensive, feels comfortable in the hand and supplied with a blunt or sharp tip. It may be a useful adjuvant to hepatic surgical procedures.

Dissection↗

Oxygen plasma etching of entire block faces improves the resolution and usefulness of serial scanning electron microscopic images.

The oxygen plasma etching technique of Humphreys et al. has been modified and applied for use on the entire block face of methacrylate and epoxy embedded biological specimens. This technique greatly improves the visualization of tissue and cellular components, including intracellular organelles. This procedure, when coupled with the use of a miniature microtome which functions inside the SEM specimen chamber, greatly increases the usefulness of serial SEM images instead of serial sections for 3-dimensional reconstructions. Although this technique is demonstrated using the central nervous system of the nudibranch mollusc Hermissenda crassicornis and the squid (Loligo pealei) fin nerve on both osmicated and non-osmicated tissue, it should have broad applicability to most biological material.

Animals↗

Ultrasonic visualization of tongue motion during speech.

A real-time ultrasonic imaging system has been developed to visualize dynamic motions of the tongue during continuous speech. Lingual motion configurations are displayed and recorded synchronously with the speech signal, time in milliseconds, and frontal and lateral views of the face during articulation. All data are videotaped and stored permanently for analysis. Data on the vertical movement of the tongue surface was obtained on 30 normal adult speakers. This technique seems to provide a useful, noninvasive technique for quantifying tongue position during speech utterances and possibly has potential as a clinical tool.

Adult↗

Design of a high resolution positron emission tomograph: the Neuro-PET.

The design of a high resolution positron emission tomograph is described. The scanner has four rings of detectors with an inside diameter of 38 cm and produces seven simultaneous slices, including three cross-slices. Each ring contains 128 bismuth germanate scintillation detectors with dimensions of 8.25 x 20 x 35 mm; adjacent crystals are separated by tapered tungsten septa that extend to within 7.5 mm of the front faces. The anticipated geometrical spatial resolution of the scanner is 4.5 mm full width at half maximum (FWHM) at the center of the image, and the sensitivity is 44,000 true counts/sec/ring (390,000 counts/sec total) for a uniform phantom 20 cm in diameter containing 1 muCi/cc activity. There are interchangeable collimators for use in high count rate studies, for narrowing the slice width from 1 cm FWHM to 5 mm FWHM, and for ultra-high resolution studies with a 2.5 mm FWHM geometrical point spread function. The electronic circuitry has separate timing and energy verification channels and can detect 95% of the coincidences with a timing window (twice the maximum time between two coincident pulses) of 14 nsec. The count rate capability of the electronics is 150,000 counts/sec/ring and 1.5 million counts/sec total.

Bismuth↗