Aged-rodent models of long-term growth hormone therapy: lack of deleterious effect on longevity

Studies were carried out to examine the effects of long-term recombinant human growth hormone (GH) therapy on longevity in rodents. In the first study, 150 18-month-old female F344 rats were divided into three groups of 50 rats per group: Group 1, solvent vehicle; Group 2, 10 microg GH/kg body weight three times per week; Group 3, 50 microg GH/kg body weight three times per week. GH and solvent vehicle therapies were started at 18 months of age and continued until all the animals died spontaneously. Serum insulin-like growth factor (IGF)-I was measured at 18 and 29 months of age and on 3-month-old rats. Serum IGF-I level decreased between 3 and 29 months of age. GH therapy reversed the decrease in a dose-dependent manner, with the 50 microg GH dose returning the serum IGF-I level to that of 3-month-old animals. However, statistical analysis revealed no significant effect of GH therapy on median life span, 10th percentile life span, or maximum life span. Similar observations on longevity were made on aged F344 male rats and on aged Balb/c mice, even when the dose of GH was increased to 1.0 mg/kg body weight two times per week. The main pathologic lesions in control animals were nephropathy, cardiomyopathy, leukemia, and testicular interstitial cell tumor; the prevalence of these lesions was not significantly altered by GH therapy. We conclude that long-term low-dose GH therapy that includes doses in the range that is given to humans in clinical trials in GH deficiency and to revert age-related physiologic declines has no overt deleterious effects on longevity and pathology in aged rodents.     

MRI for physiology and function in congenital heart disease: functional assessment of the heart preoperatively and postoperatively

We used patch-clamp recording techniques to investigate the contribution of GABA to baseline membrane properties in cultured embryonic rat hippocampal neurons. Almost all of the neurons recorded with Cl--filled pipettes and clamped at negative potentials exhibited baselines that were noticeably noisy, with microscopic fluctuations superimposed on the macroscopic holding current. A gentle steam of saline applied to the neuronal surface rapidly and reversibly reduced the baseline current and fluctuations, both of which were completely eliminated by bicuculline. Fluctuation analysis showed that the variance in the baseline current signal was exponentially distributed with estimated kinetics comparable to those activated by submicromolar concentrations of exogenous GABA. The kinetics of Cl- channels activated by endogenous GABA displayed a potential sensitivity comparable to those activated by exogenous GABA. Non-neuronal cells stably transfected with alpha1 and gamma2 GABAA receptor subunits exhibited little baseline current variance when recorded with Cl--filled pipettes. Addition of micromolar GABA to the extracellular saline or to the pipette solution induced a saline- and bicuculline-sensitive baseline current signal comparable to that recorded in hippocampal neurons. Thus, both intra- and extracellular sources of GABA could contribute to the baseline properties recorded in these cultured neurons.     

Phase-Resolved Strain Measurements in Hydrated Ordinary Portland Cement Using Synchrotron X-rays

X-ray diffraction methods developed for the determination of residual stress states in crystalline materials have been applied to study residual strains and strains because of mechanical loading of ordinary portland cement paste. Synchrotron X-rays were used to make in situ measurements of interplanar spacings in the calcium hydroxide (CH) phase of hydrated neat portland cement under uniaxial compression. The results indicate that strains on the order of 1/100 000 can be resolved providing an essentially new technique by which to measure the phase-resolved meso-scale mechanical behavior of cement under different loading conditions. Evaluation of these strain data in view of published elastic parameters for CH suggests that the CH carries a large fraction of the applied stress and that plastic interactions with the matrix are notable.     

Effect of dietary linseed oil on tumoricidal activity and eicosanoid production in murine macrophages

Diets that contain high levels of n−3 fatty acids from fish oil have been shown to significantly effect macrophage cytolytic capacity, tumor necrosis factor alpha production and eicosanoid production. The present study was undertaken to determine whether n−3 fatty acids from vegetable origin [linseed oil (LIN)] would have the same effects on murine macrophage tumoricidal capacity and eicosanoid production as would fish oil. Mice were fed for three weeks diets that contained 10% (wt/wt) of either LIN, which is high in linolenic acid (18∶3n−3), menhaden fish oil (MFO), which is high in eicosapentaenoic (20∶5n−3) and docosahexaenoic (22∶6n−3) acids, or safflower oil (SAF), which is high in linoleic acid (18∶2n−6).In vivo- orin vitro-activated macrophages were assessed for select functions. As expected, macrophages from mice fed LIN and MFO produced significantly lower levels of both prostaglandins and leukotriene C₄ when compared with macrophages from mice fed SAF. In addition, LIN and MFO macrophages were able to synthesize leuko-triene C₅, which could not be produced by macrophages from mice fed SAF. The effects of LIN, however, were not as pronounced as those of MFO. With respect to specific functions, macrophages from mice fed LIN did not have altered cytolytic capacity when compared with macrophages from mice fed SAF and activatedin vitro with either lipopolysaccharide (LPS) alone for 24 h or with LPS plus interferon gamma (IFNγ) for 5 h. Diet did not significantly alter tumoricidal capacity of macrophages activated completelyin vivo either. Specific binding of macrophages to tumor targets, nitric oxide production and the production of tumor necrosis factor alpha were found to be unaltered by LIN when compared with SAF. The results are not consistent with a general n−3 effect, as LIN could not effect the functions comparable to MFO. The results also suggest that a change in eicosanoid production may not be sufficient to modulate tumoricidal activity in macrophages.     

Uranium spectrum between 1.8 and 5.5 microns emitted from a hollow cathode

The emission spectrum of uranium has been observed in the infrared from 1.8 to 5.5 μm using the McMath Fourier transform spectrometer at the Kitt Peak National Observatory, and a water-cooled hollow cathode lamp. The wavenumber, wavelength, and relative intensity of 4418 lines between 1817 and 5598 cm^?1 that can be classified as transitions between known levels of the first and second spectra of uranium have been tabulated. In addition, wavenumbers and intensities of 4744 lines that cannot be classified in this manner are listed. Most of these are believed to be uranium emission lines. Isotope shifts are reported for 196 lines.     

Absorption of safflower oil and structured lipid preparations in patients with cystic fibrosis

Patients with cystic fibrosis (CF) and pancreatic insufficiency usually have decreased linoleic and increased oleic, palmitoleic and eicosatrienoic (20∶3ω9) acids compared to normal values of blood and tissue lipids. These changes are consistent with early essential fatty acid deficiency and are observed despite the regular use of exogenous pancreatic enzyme supplementation. As part of a study to determine the relative role of malabsorption as the etiology for the altered fatty acid status, the change in total plasma fatty acids and in area percent of plasma linoleic acid was determined in CF patients and control subjects following the ingestion of various lipid supplements, including two safflower oil preparations and two structured lipid preparations. Fasting subjects consumed 33 g of lipid in a milkshake containing 15 g of protein and 45 g of carbohydrate. Plasma samples obtained 0, 2, 4, 6 and 8 hr after the meal showed that the CF patients absorbed all preparations when administered with their regular dose of pancreatic enzyme supplement. Comparison of the patterns of increase for total plasma fatty acids and area percent of plasma linoleic acid following the administration of the different lipid supplements in CF patients and control subjects suggests that(a) malabsorption alone is not the cause of the abnormal fatty acid composition in the lipids of CF patients and that increased caloric intake along with consumption of adequate amounts of linoleic acid should improve the linoleic acid status of CF patients; (b) there may be selectively increased metabolism of certain fatty acids from the ingested lipids in the relatively malnourished CF patient compared to control subjects; and (c) conditions favoring the persistence of nonpancreatic lipases seem also to favor absorption and utilization of the structured lipid preparation containing medium chain length fatty acids and linoleic acid in CF patients compared to control subjects. Presented at the symposium on “Specialty Lipids and Their Biofunctionality”, at the annual meeting of the American Oil Chemists' Society, Philadelphia, May 1985.     

Remote atmospheric breakdown for standoff detection by using an intense short laser pulse

A remote atmospheric breakdown is a very rich source of UV and broadband visible light that could provide an early warning of the presence of chemical-biological warfare agents at extended standoff distances. A negatively chirped laser pulse propagating in air compresses in time and focuses transversely, which results in a rapid laser intensity increase and ionization near the focal region that can be located kilometers away from the laser system. Proof-of-principle laboratory experiments are performed on the generation of remote atmospheric breakdown and the spectroscopic detection of mock biological warfare agents. We have generated third harmonics at 267 nm and UV broadband radiation in air from the compression and focusing of femtosecond laser pulses. Fluorescence emission from albumin aerosols as they were illuminated by the femtosecond laser pulse has been observed.     

Geophysical imaging of stimulated microbial biomineralization

Understanding how microorganisms influence the physical and chemical properties of the subsurface is hindered by our inability to observe microbial dynamics in real time and with high spatial resolution. Here, we investigate the use of noninvasive geophysical methods to monitor biomineralization at the laboratory scale during stimulated sulfate reduction under dynamic flow conditions. Alterations in sediment characteristics resulting from microbe-mediated sulfide mineral precipitation were concomitant with changes in complex resistivity and acoustic wave propagation signatures. The sequestration of zinc and iron in insoluble sulfides led to alterations in the ability of the pore fluid to conduct electrical charge and of the saturated sediments to dissipate acoustic energy. These changes resulted directly from the nucleation, growth, and development of nanoparticulate precipitates along grain surfaces and within the pore space. Scanning and transmission electron microscopy (SEM and TEM) confirmed the sulfides to be associated with cell surfaces, with precipitates ranging from aggregates of individual 3-5 nm nanocrystals to larger assemblages of up to 10-20 microm in diameter. Anomalies in the geophysical data reflected the distribution of mineral precipitates and biomass over space and time, with temporal variations in the signals corresponding to changes in the aggregation state of the nanocrystalline sulfides. These results suggest the potential for using geophysical techniques to image certain subsurface biogeochemical processes, such as those accompanying the bioremediation of metal-contaminated aquifers.     

The Effects of Long Term Storage on Lithium Drifted Silicon Detectors

The characteristics of four (4) lithium drifted silicon surface barrier detectors have been studied. Detector noise and leakage current were measured at the beginning and end of a sixteen (16) mounth interval. The thickness of the intrinsic region, at the beginning and end of a fourteen (14) month interval, was determined by use of proton beams from the University of Southern California Linac and the University of Colorado cyclotron. Detector noise measurements were made using both a standard pulser technique and the photopeak from Ba133 . The noise and leakage were measured at -54°C, +20°C aud +60°C. The detector leakage was measured as a function of bias at +20°C. The detector thickness measurements were also performed at +20°C