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A radiative transfer model is used to quantitatively investigate aspects of the martian ultraviolet radiation environment, past and present. Biological action spectra for DNA inactivation and chloroplast (photosystem) inhibition are used to estimate biologically effective irradiances for the martian surface under cloudless skies. Over time Mars has probably experienced an increasingly inhospitable photobiological environment, with present instantaneous DNA weighted irradiances 3.5-fold higher than they may have been on early Mars. This is in contrast to the surface of Earth, which experienced an ozone amelioration of the photobiological environment during the Proterozoic and now has DNA weighted irradiances almost three orders of magnitude lower than early Earth. Although the present-day martian UV flux is similar to that of early Earth and thus may not be a critical limitation to life in the evolutionary context, it is a constraint to an unadapted biota and will rapidly kill spacecraft-borne microbes not covered by a martian dust layer. Microbial strategies for protection against UV radiation are considered in the light of martian photobiological calculations, past and present. Data are also presented for the effects of hypothetical planetary atmospheric manipulations on the martian UV radiation environment with estimates of the biological consequences of such manipulations.

Choline acetyltransferase synthesizes acetylcholine in cholinergic neurons and, in humans, may be produced in 82- and 69-kDa forms. In this study, recombinant choline acetyltransferase from baculovirus and bacterial expression systems was used to identify protein isoforms by two-dimensional SDS/PAGE and as substrate for protein kinases. Whereas hexa-histidine-tagged 82- and 69-kDa enzymes did not resolve as individual isoforms on two-dimensional gels, separation of wild-type choline acetyltransferase expressed in insect cells revealed at least nine isoforms for the 69-kDa enzyme and at least six isoforms for the 82-kDa enzyme. Non-phosphorylated wild-type choline acetyltransferase expressed in Escherichia coli yielded six (69 kDa) and four isoforms (82 kDa) respectively. Immunofluorescent labelling of insect cells expressing enzyme showed differential subcellular localization with the 69-kDa enzyme localized adjacent to plasma membrane and the 82-kDa enzyme being cytoplasmic at 24 h. By 64 h, the 69-kDa form was in cytoplasm and the 82-kDa form was only present in nucleus. Studies in vitro showed that recombinant 69-kDa enzyme was a substrate for protein kinase C (PKC), casein kinase II (CK2) and alpha-calcium/calmodulin-dependent protein kinase II (alpha-CaM kinase), but not for cAMP-dependent protein kinase (PKA); phosphorylation by PKC and CK2 enhanced enzyme activity. The 82-kDa enzyme was a substrate for PKC and CK2 but not for PKA or alpha-CaM kinase, with only PKC yielding increased enzyme activity. Dephosphorylation of both forms of enzyme by alkaline phosphatase decreased enzymic activity. These studies are of functional significance as they report for the first time that phosphorylation enhances choline acetyltransferase catalytic activity.

Acetic acid applied to the hindlimb of a frog evokes a vigorous wiping of the exposed skin. The aim of this study was to determine if acetic acid evokes this wiping response by decreasing subepidermal pH. Because acetic acid is hyperosmolar, a second aim was to determine if the osmolarity of acetic acid contributed to evoking the wiping response. In behavioral experiments, different acids or acetic acid/sodium acetate buffers at different pHs were used to evoke the wiping response. In separate experiments, subepidermal pH was measured in vitro while these same solutions were applied to samples of skin from frogs. The wiping response evoked by acetic acid was associated with a decrease in subepidermal pH to a level that has been shown to activate nociceptors. Interestingly, formic, oxalic, sulfuric, and hydrochloric acid evoked the wiping response without decreasing subepidermal pH. The osmolarity of acetic acid contributed to evoking the wiping response because buffers at subthreshold pHs evoked the wiping response. Also, the osmolarity required to evoke the wiping response depended upon the pH of the buffer. Thus, acetic acid and the buffers at pH 2.97 and 4.67 could evoke the wiping response by decreasing subepidermal pH. In contrast, formic, oxalic, sulfuric, and hydrochloric acid, as well as the buffers at pH 5.17 and 5.67, evoked the wiping response through another mechanism, perhaps by increasing subepidermal osmolarity. These studies demonstrate that both pH and osmolarity may contribute to nociception produced by algesic chemicals and may be important in inflammatory pain.

The purpose of this study was to evaluate the relative contributions of ankle and knee position to tension in the Achilles tendon and to determine whether there exists a position of plantarflexion at which the passive tensioning effect of knee extension is eliminated. Seven matched pairs of fresh-frozen cadaver lower extremities were tested. A buckle transducer was used to measure forces in the tendon throughout the full range of knee motion, with the hindfoot fixed. Positioning the hindfoot in 20 degrees to 25 degrees of plantarflexion effectively eliminates tension in the Achilles tendon, regardless of knee position. This information is directly applicable both to the nonoperative treatment of ruptures of the Achilles tendon employing a short leg cast and to surgical repairs, in which tension must be controlled precisely.

The detection of organics on Mars remains an important scientific objective. Advances in instrumentation and laboratory techniques provide new insight into the lower level detection limit of complex organics in closely packed media. Preliminary results demonstrate that algae present in a palagonite medium do exhibit a spectral reflectance feature in the visible range for dry mass weight ratios of algae to palagonite greater than 6%--which corresponds to 30 mg algae in a 470 mg (just optically thick (< 3 mm) layer) palagonite matrix. This signature most probably represents chlorophyll a, a light harvesting pigment with an emission peak at 678 nm.

The field of study that deals with the origins of life does not have a consensus for a theory of life's origin. An analysis of the range of theories offered shows that they share some common features that may be reliable predictors when considering the possible origins of life on another planet. The fundamental datum dealing with the origins of life is that life appeared early in the history of the Earth, probably before 3.5 Ga and possibly before 3.8 Ga. What might be called the standard theory (the Oparin-Haldane theory) posits the production of organic molecules on the early Earth followed by chemical reactions that produced increased organic complexity leading eventually to organic life capable of reproduction, mutation, and selection using organic material as nutrients. A distinct class of other theories (panspermia theories) suggests that life was carried to Earth from elsewhere--these theories receive some support from recent work on planetary impact processes. Other alternatives to the standard model suggest that life arose as an inorganic (clay) form and/or that the initial energy source was not organic material but chemical energy or sunlight. We find that the entire range of current theories suggests that liquid water is the quintessential environmental criterion for both the origin and sustenance of life. It is therefore of interest that during the time that life appeared on Earth we have evidence for liquid water present on the surface of Mars.

CNR studies were performed for human intracranial vessels in 3D MRA data sets. The CNR dependency of different imaging parameters, such as flip angle, field of view, echo time, repetition time, and echo readout symmetry, was studied for vessels in the region of the circle of Willis. A theoretical model was developed for MR vascular imaging based on the Bloch equations and Fourier imaging theory. This model predicts the MR image intensity of vessels from basic subject parameters, such as the relaxation times of blood and stationary tissue, vessel dimension, and flow velocity, and the parameters of the imaging technique, such as flip angle, voxel volume, repetition time, and echo time. For most experiments, the model was found to fit the experimental results well. The validity of this model allows the optimization of imaging parameters to maximize vessel CNR in MR angiography.

A 3D projection reconstruction (3DPR) method was used to obtain in vivo 11B images in a large canine brain tumor model and in a human infused with borocaptate sodium (BSH). Studies were performed in dogs with and without gliosarcomas implanted and grown to a size of 2-3 cm. The 3DPR method demonstrates a signal-to-noise ratio (SNR) that allows qualitative kinetic studies of the boron compound in normal and tumor tissue of the head. The measurements indicate initial uptake of the BSH compound in tumor to be less than that in muscle with no uptake in normal brain tissue. Moreover, uptake of BSH in tissue was found to lag the boron concentration in blood with delays that depend on tissue type. In addition, the first human boron images were obtained on a patient who underwent surgical resection and volumetric debulking of a large (7 cm) glioblastoma multiforme. BSH was readily taken up in residual tumor tissue, while diffusion into the resection volume was slower.

The perivertebral space is in the midline, in the deep tissues of the neck, and can be identified from the skull base above to the mediastinum below. It is a discrete space completely enclosed by the deep layer of deep cervical fascia. The fascial attachments of the perivertebral space divide it into two areas, the anterior prevertebral and posterior paraspinal portions. We made a retrospective analysis of the radiologic and clinical records of 52 patients with lesions in the perivertebral space, to identify the imaging features that mark a lesion as originating in the perivertebral space and define the spectrum of pathology which occurs in the space. Mass lesions present in the prevertebral or paraspinal portions. In the former they usually involve the vertebral body, displacing the prevertebral muscles anteriorly. Epidural extension from lesions in the perivertebral space proper is common. Masses in the paraspinal perivertebral space usually displace the paraspinal muscles away from the spine. We found 9 inflammatory lesions, 29 malignant and 6 benign tumors, and 8 miscellaneous lesions.

For a variety of reasons, small vessels have low signal intensity in magnetic resonance angiography. When the vessel signal intensity is lower than the signal intensity of background tissues, these vessels tend not to be visible on maximum-intensity-projection images. The authors developed a nonlinear second-difference spatial filtering technique that enhances the details of small vessels while suppressing both noise and uniform background tissue. Two similar nonlinear second-difference filters are presented and compared with the linear Laplacian second-difference filter. To evaluate the performance of these filters, they were applied to intracranial three-dimensional time-of-flight MR angiographic data and the results compared with the vessel enhancement obtained with a simple second-difference Laplacian filter and with magnetization transfer contrast (MTC) techniques. The comparisons demonstrated that nonlinear filtering and MTC techniques result in similar improvement in small-vessel visibility and apparent continuity. A quantitative comparison demonstrated that the improvement in the contrast-to-noise ratio is much greater with the nonlinear filters than the Laplacian filter.

The transection and superposition relationships among channels, chaos, surface materials units, and other features in the circum-Chryse region of Mars were used to evaluate relative age relationships and evolution of flood events. Channels and chaos in contact (with one another) were treated as single discrete flood-carved systems. Some outflow channel systems form networks and are inferred to have been created by multiple flood events. Within some outflow channel networks, several separate individual channel systems can be traced to a specific chaos which acted as flood-source area to that specific flood channel. Individual flood-carved systems were related to widespread materials units or other surface features that served as stratigraphic horizons. Chryse outflow channels are inferred to have formed over most of the perceivable history of Mars. Outflow channels are inferred to become younger with increasing proximity to the Chryse basin. In addition, outflow channels closer to the basin show a greater diversity in age. The relationship of subsequent outflow channel sources to the sources of earlier floods is inferred to disfavor episodic flooding due to the progressive tapping of a juvenile near-surface water supply. Instead, we propose the circum-Chryse region as a candidate site of past hydrological recycling. The discharge rates necessary to carve the circum-Chryse outflow channels would have inevitably formed temporary standing bodies of H2O on the Martian surface where the flood-waters stagnated and pooled (the Chryse basin is topographically enclosed). These observations and inferences have led us to formulate and evaluate two hypotheses: (1) large amounts of the sublimated H2O off the Chryse basin flood lakes precipitated (snowed) onto the flood-source highlands and this H2O was incorporated into the near surface, recharging the H2O sources, making possible subsequent deluges; and (2) ponded flood-water in Chryse basin drained back down an anti basinward dipping subsurface layer accessed long the southern edge of the lake, recharging the flood-source aquifers. H2O not redeposited in the flood-source region was largely lost to the hydrologic cycle. This loss progressively lowered the vitality of the cycle, probably by now killing it. Our numerical evaluations indicate that of the two hypotheses we formulated, the groundwater seep cycle seems by far the more viable. Optimally, approximately 3/4 of the original mass of an ice-covered cylindrical lake (albedo 0.5, 1 km deep, 100-km radius, draining along its rim for one quarter of its circumference into substrata with a permeability of 3000 darcies) can be modeled to have moved underground (on timescales of the order of 10(3) years) before the competing mechanisms of sublimation and freeze down choked off further water removal. Once underground, this water can travel distances equal to the separation between Chryse basin and flood-source sites in geologically short (approximately 10(6) year-scale) times. Conversely, we calculate that optimally only approximately 40% of the H2O carried from Chryse can condense at the highlands, and most of the precipitate would either collect at the base of the highlands/lowlands scarp or sublimate at rates greater than it would accumulate over the flood-source sites. Further observations from forthcoming missions may permit the determination of which mechanisms may have operated to recycle the Chryse flood-waters.

In this paper the problem of small structure visualization in magnetic resonance imaging (MRI) is considered. The relationship between the structure and the image intensities is defined in terms of the voxel sensitivity function (VSF). Using the VSF, the spatial dependence of the voxel signal for small spheres and cylinders is computed. Although the spatial fluctuation is smaller in the MRI VSF than that which would be obtained from a uniformly sensitive cubical voxel, the deviation still results in significant signal loss near the edges and corners of the voxels. Finally, the VSF formalism is used to demonstrate the improvement in signal uniformity that can be obtained by using zero-filled (band-limited or sinc) interpolation.

Objective: Time-of-flight (TOF) MR angiography has continued to evolve during the past few years. Signal loss due to flow saturation is a major problem of single-volume (slab) three-dimensional (3D) TOF technique. A multislab 3D TOF method, multiple overlapping thin slab acquisition (MOTSA), shows decreased sensitivity to the effects of flow saturation and therefore should result in better images., Subjects and Methods: To evaluate the difference between MOTSA and the traditional single-volume 3D TOF techniques, we performed sequential, location-matched studies in 17 prospectively chosen patients with intracranial vascular abnormalities. All MOTSA and 3D TOF images were obtained after cut-film or 1024 digital angiography., Results: According to specific criteria, abnormalities were better visualized with the MOTSA technique than with the single-volume 3D TOF technique. The difference was most marked in patients with more complex vascular abnormalities., Conclusion: We conclude that MOTSA is better than single-volume 3D TOF for showing intracranial abnormalities. The major advantage of MOTSA is decreased sensitivity to flow saturation.

We describe two MR angiographic methods of diagnosing subclavian steal in each of three patients. By using phase-directional information from a single two-dimensional phase-contrast sequence, we were able to show that the direction of flow in the affected vertebral artery was reversed. The same vertebral artery showed no signal on a 2-D time-of-flight sequence with a concatenated presaturation pulse applied above each section.

Partial-volume artifacts reduce vessel contrast and continuity (especially in small vessels) in magnetic resonance (MR) angiography. The authors applied zero-filled (band-limited) interpolation to three-dimensional (3D) MR angiograms to reduce partial-volume artifacts. They demonstrated that zero-filled interpolation can also be implemented by means of voxel shifting in real space. Voxel-shifted interpolation is much less computer memory intensive than conventional zero-filled interpolation. They numerically simulated the contrast loss due to partial-volume artifacts and contrast recovery obtained with zero-filled interpolation. Zero-filled interpolation in all three orthogonal directions was applied to 3D MR angiography data sets from 29 human studies. These studies were obtained with the three commonly used 3D MR angiography techniques: 3D time of flight, multislab 3D time of flight, and 3D phase contrast. A substantial improvement in vessel contrast and vessel continuity was observed in all cases.

Purpose: Two magnetic resonance (MR) angiography pulse sequences, two-dimensional (2D) time of flight (TOF) and multislab three-dimensional (3D) TOF, were compared for ease of application and capability of depicting the arterial trifurcation in candidates for vascularized fibular grafts., Patients and Methods: Both 2D TOF and multislab 3D TOF MR angiography procedures were performed to image the lower legs of 15 healthy volunteers and six patients. Three radiologists evaluated each study for the number of trifurcation vessels depicted at the knee and at the ankle, the corresponding degree of confidence, and the presence of anatomic variants., Results: All trifurcation vessels were identified at the level of the knee with a high degree of confidence. Usually two vessels could be identified at the ankle with a slightly lower degree of confidence. A higher number of vessels were identified at the ankle with the 2D TOF technique than with the 3D TOF technique. A number of anatomic variants were identified. Anatomy of all six patients was identified correctly and confirmed at surgery., Conclusion: Both 2D TOF and multislab 3D TOF are useful techniques to define the arterial anatomy of the lower leg and have proved valuable in preoperative planning for vascularized grafts. Vessel visualization at the level of the ankle was superior with the 2D TOF technique.

We have constructed a model that predicts the evolution of CO2 on Mars from the end of the heavy bombardment period to the present. The model draws on published estimates of the main processes believed to affect the fate of CO2 during this period: chemical weathering, regolith uptake, polar cap formation, and atmospheric escape. Except for escape, the rate at which these processes act is controlled by surface temperatures which we calculate using a modified version of the Gierasch and Toon energy balance model (1973, J. Atmos. Sci. 30, 1502-1508). The modifications account for the change in solar luminosity with time, the greenhouse effect, and a polar and solar equatorial energy budget. Using published estimates for the main parameters, we find no evolutionary scenario in which CO2 is capable of producing a warm (global mean temperatures>250 K) and wet (surface pressures>30 mbar) early climate, and then evolves to present conditions with approximately 7 mbar in the atmosphere, <300 mbar in the regolith, and <5 mbar in the caps. Such scenarios would only exist if the early sun were brighter than standard solar models suggest, if greenhouse gases other than CO2 were present in the early atmosphere, or if the polar albedo were significantly lower than 0.75. However, these scenarios generally require the storage of large amounts of CO2 (>1 bar) in the carbonate reservoir. If the warm and wet early Mars constraint is relaxed, then we find best overall agreement with present day reservoirs for initial CO2 inventories of 0.5-1.0 bar. We also find that the polar caps can a profound effect on how the system evolves. If the initial amount of CO2 is less than some critical value, then there is not enough heating of the poles to prevent permanent caps from forming. Once formed, these caps control how the system evolves, because they set the surface pressure and, hence, the thermal environment. If the initial amount of CO2 is greater than this critical value, then caps do not form initially, but can form later on, when weathering and escape lower the surface pressure to a point at which polar heating is no longer sufficient to prevent cap formation and the collapse of the climate system. Our modeling suggests this critical initial amount of CO2 is between 1 and 2 bar, but its true value will depend on all factors affecting the polar heat budget.

Purpose: 1) To evaluate the scope of imaging findings seen with spin-echo MR and MR angiography (MRA) in patients with pulsatile tinnitus; 2) to determine whether MRA adds additional imaging information (to that provided by spin-echo MR) necessary for determining the cause of pulsatile tinnitus; and 3) to suggest MR and MRA imaging techniques for evaluation of patients with pulsatile tinnitus., Methods: Forty-nine patients with pulsatile tinnitus were evaluated with MR and MRA. Seventeen of these patients had conventional angiography., Results: Vascular lesions or paraganglioma were demonstrated in 28 patients. Of these 28 lesions, the majority were seen best (46%) or only (36%) on MRA. The spectrum of lesions detected included dural arteriovenous fistula (nine), extracranial arteriovenous fistula (three), paraganglioma (five), jugular bulb variants (three), aberrant internal carotid artery (one), internal carotid artery stenosis (one), tortuous internal carotid artery (one), carotid dissection with pseudoaneurysm (one), stenosis of the transverse sinus (two), and arteriovenous malformation (two)., Conclusions: MRA, in conjunction with spin-echo imaging, markedly enhances the ability of MR to diagnose the lesions responsible for pulsatile tinnitus.

Preliminary work has demonstrated that dynamic contrast material-enhanced magnetic resonance imaging improves the detection sensitivity for pituitary microadenomas. The authors present a new method of obtaining dynamic contrast-enhanced pituitary images with a short TR/TE fast spin-echo technique. This approach allows acquisition of contrast-enhanced spin-echo images with high temporal and spatial resolution. The new technique is applied in a small group of patients and control subjects.

Purpose: To determine whether MR angiography can be used to differentiate between the two vascular causes of bithalamic hyperintensity on T2-weighted MR images: "top of the basilar" artery occlusion and deep cerebral vein thrombosis., Methods: A retrospective review identified six patients with bithalamic T2 hyperintensity of vascular causes. MR angiography was performed in four patients, MR angiography and conventional angiography in one patient, and conventional angiography in one patient. Data pertaining to clinical presentation and hospital course were collected. MR angiographic techniques were multislab overlapping three-dimensional time-of-flight, 2-D time-of-flight, and 2-D phase-contrast., Results: Three cases of top of the basilar artery occlusion and three cases of deep cerebral vein thrombosis were recognized. In all cases, T2 hyperintensity in a vascular distribution suggested cerebral occlusive disease. Infarction involving the thalami and basal ganglia was present in two cases of deep cerebral vein thrombosis. Infarction of the thalami, mesodiencephalic region, and cerebellar hemispheres was present in two cases of basilar artery occlusion. Bithalamic infarction alone was seen in one case of deep cerebral vein thrombosis and one case of basilar artery occlusion. In the five cases in which MR angiography was used, this technique accurately distinguished the vessels involved (arterial or venous)., Conclusion: MR angiography is a useful adjunct to MR imaging in the evaluation of bithalamic T2 hyperintensity. It does help distinguish between the two vascular causes: top of basilar artery occlusion and deep cerebral vein thrombosis.

Ubiquitin was localized by immunofluorescence microscopy during post-mating histolysis of fibrillar flight muscle in female fire ants, Solenopsis spp. Normal muscles, as well as histolysing muscles from artificially inseminated and haemolymph-injected females contained ubiquitin in association with nuclei, Z-lines, myofilaments and mitochondria. However, the density of the ubiquitin immunoreaction was markedly increased in the nuclei, Z-lines and mitochondria of degenerating tissues 6, 12 and 24 h posttreatment. At these times the heaviest immunoreactivity for ubiquitin was seen in association with the nuclei, Z-lines and mitochondria. Immuno-controls, incubated in the absence of the primary antibody, showed no similar immunostaining. When insemination was preceded by the injection of actinomycin D, muscle degradation was significantly depressed after a 24-h period. Also, ubiquitin immunofluorescence was markedly reduced in tissues pre-treated with actinomycin D. These observations suggest that insemination increases the ubiquitination of specific myofibrillar proteins destined for degradation.

The purpose of this study was to evaluate the ability of a recently developed porous calcium polyphosphate bioceramic (CPB) to function as a bone graft substitute. After six weeks, postsurgical extraction of the mandibular first and second molars, alveolar ostectomies were performed bilaterally in five dogs. The ridge forms were then restored using the CPB implant material on one side and the autogenous bone obtained from the contralateral ostectomy site on the other. The graft and implant sites were retrieved after 4 months and decalcified and undecalcified sections were prepared for special staining (modified Attwood) and subsequent light microscopy and histomorphometry. In addition, the undecalcified sections were prepared for histometry using backscattered electron imaging (BSEI). Histologically, the CPB implants showed extensive vascularization and cellularity within an "invading" loose connective tissue matrix. On the opposite side, the loose connective tissue of the autografts showed hypovascularity and hypocellularity. Neither the implants nor the autografts showed any histologic evidence of an inflammatory reaction. Using light microscopic histomorphometry, the implants showed a higher incidence of union than the autografts. On BSEI histometry, the CPB implants showed significantly greater new bone formation than the autografts. This study reveals that porous CPB possesses certain characteristics essential for the "ideal" implantable bone substitute necessary for the repair of craniofacial and other bony defects.

Magnetic resonance angiography (MRA) is a novel technique that uses gradient echo pulse sequences and computer postprocessing technology to create vascular-flow images. The technique is easy to apply, noninvasive, and frequently yields information not available by other noninvasive means. The utility and benefits of MRA are amply documented by clinical studies in the neuroimaging literature. This article reviews the techniques of MRA and the current literature in the application of MRA in pediatric imaging. Illustrative cases demonstrating the use of MRA in pediatric neuroradiology are presented. The utilization of MRA in congenital lesions such as aberrant internal carotid artery and arteriovenous malformation and in differing causes of ischemic disease is highlighted. There is an ever-expanding number of applications of MRA in pediatric neuroimaging. Despite the lack of standardized protocols, with a thorough knowledge of the basic principles, MRA can be successfully applied in many imaging situations. The ease of use and noninvasive nature of MRA make it an ideal tool in the evaluation of the pediatric neurovasculature.

Rationale and Objectives: The authors report on the development and preliminary validation of a technique for measuring contrast-to-noise ratio (CNR) at all points along selected vessel segments in the original three-dimensional magnetic resonance angiography (MRA) dataset., Methods: Contrast-to-noise ratio dependencies on flow rate, field of view, and flip angle were measured on images from a conventional time-of-flight MRA pulse sequence using constant flow in a branching vascular phantom. An estimate of the inherent variability of the technique was obtained from multiple scans of a flow phantom and a human volunteer., Results: The overall standard deviation (SD) of the CNR was found to be approximately 6.1% of the average CNR value for the flow phantom study and 7.3% for the human study. Vessel CNR was found to increase with field of view and was found to become nonuniform for low flow rate and/or high flip angles., Conclusion: In general, such CNR measurements allow the investigation of the mechanism of signal loss and general technique optimization in MRA.

The velocity-phase relationship intrinsic to phase-contrast magnetic resonance (MR) angiography permits the quantitative and qualitative assessment of blood flow. The ability to measure velocity and vessel cross-sectional area allows noninvasive assessment of volume flow rate (VFR) in the internal carotid artery (ICA). Phase-contrast techniques also demonstrate flow direction. Using two-dimensional cine phase-contrast angiography, the authors evaluated VFR in the ICA and collateral flow about the circle of Willis in 15 patients with ischemic neurologic symptoms. The VFR in each carotid artery was correlated with the degree of stenosis and presence or absence of abnormal circle of Willis collateral flow. There was a correlation between a decrease in VFR and abnormal circle of Willis collateral flow. In addition, a correlation between severe stenosis and a decrease in VFR was found. In patients with ischemic neurologic symptoms without severe stenosis (< 70% diameter stenosis), no decrease in VFR was seen. It is hoped that flow quantification and directional flow imaging with phase-contrast angiography will help further characterize carotid artery occlusive disease by enabling assessment of VFR changes associated with ischemic neurologic symptoms. This study also supports the hypothesis that two mechanisms--hemodynamic and embolic--play a role in ischemic neurologic symptoms.

In Solenopsis spp., muscle histolysis or breakdown is a normal process in females and is initiated in the flight muscles only immediately after a mating flight. Information regarding the presence of the oxyradical scavenging enzyme superoxide dismutase (SOD) and the formation of the radical oxygen intermediate superoxide (SO) during the early stages of flight muscle histolysis in this insect was investigated. In normal fibrillar flight muscles from control animals, SOD was immunolocalized to vesicular and tubular components of the sarcotubular system. Lanthanum tracer studies indicated that some of these SOD-positive structures might be tubulovesicles continuous with the extracellular space. Following the injection of virgin alates with experimental haemolymph obtained from artificially inseminated females, the membrane delimited elements of the sarcotubular system became increasingly swollen and dilated with time (from 60 to 120 minutes postinjection) with a concomitant decrease in SOD activity and an increase in oxyradical formation. Many similar vesicles were lanthanum-positive. SO was not seen in the sarcoplasmic vesicles and tubules of control insects. The biochemical quantification of SO release over a 2-hour period showed a marked increase in oxyradical formation following treatment with the experimental haemolymph in comparison to control insects. Also, the addition of superoxide dismutase depressed SO formation under these conditions. Despite the histochemical and biochemical changes seen in the muscles of experimental insects, by 2 hours post-treatment there was no evidence of muscle necrosis. From these studies on flight muscle histolysis/necrosis in Solenopsis it appears that the formation of oxyradicals might represent an early event in myopathogenesis and subsequent tissue involution. The generation of SO is more than likely to be associated with alterations in the normal structure, biochemistry and permeability of the biomembranes which delimit the sarcotubular system.

The effect of insulin and insulin like growth factors I and II on sunflower, watermelon and cucumber cotyledons has been examined. Each peptide stimulates an increase in the activity of several glyoxysomal enzymes which catalyze the conversion of fat to carbohydrate. These results provide the first evidence for the action of insulin and insulin like growth factors in plants.

Practical approaches to optimization of the use of gadolinium in MR imaging comprise a range of advances in data-acquisition techniques and pulse sequences that augment tissue contrast and reduce scanning times, increasing throughput and patient comfort. In addition to the effects of magnetic field strengths and manipulation of contrast doses for routine spin-echo (SE) imaging, several approaches are reviewed. These include: fat suppression, which helps to resolve enhancing lesions from tissues with inherently high signal on post-gadolinium T1-weighted imaging; gradient-echo (GRE) and partial radio-frequency (RF) echoplanar techniques, which tend to reduce data acquisition times; MR angiography, which enables elucidation of slow-flow vessels and mass-vessel relationships; and three-dimensional GRE scan displays, which relate lesion location to regional and surface anatomy.

Single volume three-dimensional (3D) time-of-flight (TOF) MR angiography is the most commonly used noninvasive method for evaluating the intracranial vasculature. The sensitivity of this technique to signal loss from flow saturation limits its utility. A recently developed multislab 3D TOF technique, MOTSA, is less affected by flow saturation and would therefore be expected to yield improved vessel visualization. To study this hypothesis, intracranial MR angiograms were obtained on 10 volunteers using three techniques: MOTSA, single volume 3D TOF using a standard 4.9 ms TE (3D TOFA), and single volume 3D TOF using a 6.8 ms TE (3D TOFB). All three sets of axial source images and maximum intensity projection (MIP) images were reviewed. Each exam was evaluated for the number of intracranial vessels visualized. A total of 502 vessel segments were studied with each technique. With use of the MIP images, 86% of selected vessels were visualized with MOTSA, 64% with 3D TOFA (TE = 4.9 ms), and 67% with TOFB (TE = 6.8 ms). Similarly, with the axial source images, 91% of selected vessels were visualized with MOTSA, 77% with 3D TOFA (TE = 4.9 ms), and 82% with 3D TOFB (TE = 6.8 ms). There is improved visualization of selected intracranial vessels in normal volunteers with MOTSA as compared with single volume 3D TOF. These improvements are believed to be primarily a result of decreased sensitivity to flow saturation seen with the MOTSA technique. No difference in overall vessel visualization was noted for the two single volume 3D TOF techniques.

The enzymatic activities unique to the glyoxylate cycle of higher plants and certain lower invertebrates, isocitrate lyase and malate synthase, have been demonstrated in homogenates prepared from human liver. Human liver can also carry out cyanide-insensitive fatty acid oxidation from palmitate. Utilizing light microscopic immunocytochemistry with an antibody produced against Euglena malate synthase, this enzyme localizes in numerous ovoid granules in human hepatocytes. Also, immunocytochemistry using antibodies produced against rat fatty acyl-CoA oxidase showed that this enzyme was localized in similar structures. With routine cytochemistry, catalase was seen in identical granular bodies. Both catalase and fatty acyl-CoA oxidase are peroxisomal enzymes. The presence of malate synthase in liver homogenates was further confirmed by Western blot analysis. These data suggest that the human liver may be capable of utilizing the carbon backbone of fatty acids for carbohydrate synthesis since the glyoxylate cycle in lower organisms subserves this anabolic function.

In conclusion, inflammatory sinonasal disease can be conveniently grouped into five distinct radiological patterns, each with a different therapeutic course and surgical options. A more precise interpretation of SSCT scans is rendered when inflammatory sinonasal disease is categorized into these distinct radiological patterns. The three obstructive patterns occur due to dysfunction of the mucociliary drainage routes of the paranasal sinuses and result in specific diagnostic patterns that are recognizable on coronal SSCT examinations. When one of the three obstructive patterns is identified, detailed attention can be directed to the likely site of occlusion, with possible definition of a specific etiology. A detailed road map of relevant surgical anatomy and pathology is then available for the endoscopic surgeon. This road map can then be used for a more directed and specific functional endoscopic sinonasal surgery. This results in improved patient care and surgical result.

In this study, the breast carcinoma-reactive monoclonal antibody 15A8 and a site-specific immunoconjugate of the antibody, 15A8-glycyl-tyrosyl-(N-epsilon-diethylenetriamine pentaacetic acid)-lysine (15A8-GYK-DTPA), were characterized by immunohistological methods for reactivity with normal and neoplastic human tissues and normal cynomolgus monkey tissues. In addition, 15A8-GYK-DTPA labeled with 111In was assessed by in vivo imaging and pharmacokinetic studies for localization to human tumor xenografts in nude mice. The native antibody and the site-specific immunoconjugate exhibited similar limited reactivity with normal human tissues. Specifically, epithelial structures, including normal breast epithelium, lung alveoli, bronchial epithelium and glands, liver bile ducts, pancreatic ducts, kidney distal and collecting tubules, epidermal and esophageal epithelium, endometrial glands, and thymic Hassall's corpuscles, were reactive. Normal monkey tissues stained with 15A8 exhibited a similar pattern of reactivities. Antibody 15A8 reacted broadly with epithelium-derived tumors; more than 60% of the cells in all of the breast, colon, non-small cell lung, ovarian, prostate, bladder, and renal carcinomas tested expressed the antigen. In contrast, a variety of nonepithelial neoplasms, including lymphomas, melanomas, sarcomas, and small cell lung carcinomas, were nonreactive. 15A8-GYK-DTPA-111In administered i.v. rapidly localized to and imaged both MX-1 and MCF-7 human breast carcinoma xenografts in nude mice, reaching maximal levels of about 20% of injected dose/g of tumor within 4 days. No unusual localization to any nontumor tissue or organ was seen; the level of radioactivity in the normal tissues and organs was at or below that seen in the blood. Furthermore, the immunoconjugate did not accumulate in xenografts of the antigen-negative breast carcinoma ZR-75-1, which indicates that tumor localization was antigen specific. Pharmacokinetic studies in cynomolgus monkeys suggested that significant amounts of 15A8-GYK-DTPA-111In did not localize to normal epithelia and demonstrated that the immunoconjugate was not toxic. These findings suggest that antibody 15A8 may be useful in the diagnosis and therapy of breast cancer and possibly other carcinomas.

Periodontal soft tissues were cleaved from freshly extracted human teeth. Tissues were then prepared for subsequent biochemical and morphological studies according to the following plan: 1) immediate immersion in liquid nitrogen for the biochemical assay of superoxide dismutase (SOD); 2) immediate fixation prior to routine preparation for routine transmission electron microscopy; 3) immediate fixation prior to preparation for electron microscopic immunohistochemistry. Biochemical analysis showed that the human periodontal ligament contained about twice as much SOD activity as human skin (dermis), but considerably less enzyme activity than that seen in red blood cells. Interestingly, periodontal SOD activity appeared to decrease with age. Immunohistochemistry localized enzyme activity to the periphery of matrix collagen fibrils and to the glycocalyx of tissue fibroblasts. The pathophysiology of this enzyme regarding inflammatory diseases such as periodontitis is discussed.

Information regarding the presence of the free radical scavenging (inactivating, dismutating) enzyme superoxide dismutase in human dental pulp was sought. Free radicals, such as the superoxide anion radical (O2-) and the hydroxyl anion radical (OH.), are powerful biological oxidants produced by phagocytes during the normal tissue response to injury and infection. Also produced is hydrogen peroxide (H2O2), an aggressive oxygen species formed by the reaction of superoxide with itself, i.e., a dismutation in which one molecule of O2- is oxidized by the other. These three reactive oxygen intermediates serve as part of the normal host biological defense mechanism for the inactivation of microorganisms and the breakdown of their toxic products. Both normal and inflamed dental pulps were assayed for the presence of this enzyme. Superoxide dismutase activity was identified in the normal pulpal tissues. There was a slight decrease in activity with age. In the inflamed pulpal tissues, enzyme activity was markedly and significantly increased in comparison to that in the normal tissues. These observations indicate that human dental pulp possesses an endogenous defense mechanism designed to protect the tissue components (cells and matrix) from the toxic effects of the reactive oxygen intermediates. In this regard, the inflammatory response of this specialized and somewhat isolated (compartmentalized) tissue is not unlike that seen in other connective tissues.

Special and specific immunohistochemical techniques as well as routine transmission electron microscopy were used to identify the presence of von Willebrand factor (vWF), a blood clotting factor essential to normal hemostasis, and Weibel-Palade bodies (WPB's), respectively, in the endothelial cells lining the blood vessels from both normal and inflamed human pulpal tissues. In human endothelial cells, WPB's are peculiar and specialized organelles which store vWF. All classes of blood vessels (capillaries, arterioles, arteries, venules, and veins) were vWF positive. The fine structural studies showed similar results with regard to the presence of WPB's. Interestingly, morphometric analyses conducted on the same tissues using either light or transmission electron microscopy showed that significantly more vWF-positive blood vessels were seen in the inflamed tissues. In agreement with the latter observation, transmission electron microscopy showed that more vascular endothelial cells contained WPB's in the inflamed tissues when compared with the normal tissues. From this it appears that during pulpal inflammation, the cascade of events associated with hemostasis may be activated with the increased synthesis and release of vWF by endothelial cells.

Information regarding the cytopathologic mechanism of action of the retinoids [isotretinoin (IR) and 4-oxo-isotretinoin (4-OIR)] on neural crest cells (NCCs) in culture was sought. Those pathophysiologic alterations in cell metabolism studied were: cell blebbing (xieosis), free radical formation, cell viability, and cellular calcium homeostasis. Cells were treated with IR or 4-OIR in the presence of high (1.4 mM) and low (5.0 microM) levels of extracellular calcium ions. Recently developed techniques utilizing fluorescent molecular probes for calcium analyses, i.e., Fura 2AM, were used to study the effects of these drugs on the cytosolic calcium concentration of NCCs. The effects of IR and 4-OIR on NCC viability, [Ca++]int, were contrasted with the effects of certain sulfhydryl drugs (HgCl2, NEM, PCMBS) and calcium ionophores (ionomycin, A23187), agents known to perturb cell membranes, increase cytosolic calcium loads, and induce cell injury and subsequent cell death. Both retinoids were shown to induce an increase in the generation of superoxide radicals (SO) and increase the influx of calcium ions by the NCCs, thus increasing [Ca++]int by several hundred percent within 5 to 10 min. The liberation of SO was calcium dependent. These early effects were accompanied by an increase in cell blebbing activity. Also, a significant decrease in NCC viability was seen as early as 10 min after the addition of IR or 4-OIR to the incubation medium. 4-OIR proved to be the more potent of the two retinoids tested. The severity of these effects on NCC metabolism was dependent on medium calcium concentration with all changes being increased in the presence of the higher extracellular calcium levels. From the data presented it appears as though the retinoids cause a rapid elevation in cytosolic [Ca++]int possibly by purturbing the integrity of the cell membrane, denaturing membrane Ca-ATPase activity, or both. Retinoid-induced changes in membrane activity are evidenced by increased surface blebbing and superoxide formation. The prolonged elevation of intracellular [Ca++] may be directly related to depressed NCC viability and thus explain the known teratogenic effects of these drugs and their relationship to ectomesenchymal cell hypoplasia and craniofacial dysmorphogenesis.

New methods of tissue preparation were developed to study the morphology and distribution of calcium ions in duodenal enterocytes from normal, rachitic, and vitamin D-replete (either cholecalciferol [CC] or 1,25-dihydroxycholecalciferol [1,25-DHCC] treated) chicks. Frozen hydrated sections were prepared from cryofixed tissues by ultracryomicrotomy at -125 degrees C. Sections were subsequently freeze-dried by increasing the temperature to -100 degrees C. The latter temperature was maintained throughout both the structural and elemental analyses. In cells from normal, rachitic, and vitamin D-treated [CC] animals the brush border from lanthanum-infused tissues was electron dense and calcium-lanthanum positive by x-ray analysis. In the absence of lanthanum, i.e., sucrose-infused duodena, the microvilli were still calcium positive. In the terminal web region of normal and CC-treated enterocytes, numerous, apparently interconnected, tubules and vesicles were seen. Vacuole-like structures were also seen. Such structures were especially prominent in the enterocytes from the vitamin-treated [CC] animals. Except for the vacuoles, the tubules and vesicles were electron dense in the lanthanum-infused duodena, and clear in sucrose-infused tissues. In both instances, the structures were calcium positive. Similar, but even larger structures were seen below the terminal web. Here however, the tubules and vesicles seemed to be organized into multiple complex interconnecting networks, i.e., tubulo-vesicular complexes. Both the tubules and the vesicles seemed to be interconnected via smaller channel-like entities. The extensiveness of this structure was better appreciated in the enterocytes from lanthanum-infused tissues, where it appeared similar in structure and complexity to an en face view of the sarcoplasmic reticulum of skeletal muscle. These intestinal complexes were less well developed, decreased in number, and quite often absent, in the apical cytoplasm of absorptive cells from rachitic chicks. In the enterocytes from animals treated for 24 hours with 1,25-DHCC, the same highly developed tubulo-vesicular networks were again seen in the enterocyte apical cytoplasm. They were even more developed in the 1,25-DHCC-treated animals. All structures were intensely calcium positive in enterocytes from both the lanthanum- and the sucrose-infused preparations. Numerous endocytotic (pinocytotic) vesicles were seen at the lumenal plasmalemma. Similar structures were also apparent in the terminal web region of the 1,25-DHCC-treated enterocytes. Exocytotic vesicles were seen at the apical aspect of the lateral cell membrane, below the level of the junctional complex. All components of this unique system contained high concentrations of calcium.(ABSTRACT TRUNCATED AT 400 WORDS)

We have employed a simple climate model of early Mars in order to estimate the duration of ice-covered lakes after the onset of freezing conditions on Mars. The critical parameter determining the existence of ice-covered lakes is the existence of peak seasonal temperatures above freezing. The peak temperature occurs at the subsolar point at perihelion. We use the weathering model of Pollack et al. (Icarus 71, 203-224, 1987) to compute the pressure and temperature evolution of the atmosphere. We have included the variability of the solar luminosity. We find that if there was a source of ice to provide meltwater, liquid water habitats could have been maintained under relatively thin ice covers for up to 700 million years after mean global temperatures fell below the freezing point. At this point, the mean annual temperature is 227 K, and the pressure of atmospheric CO2 is about 0.5 bar. Without the presence of stable bodies of liquid water, it is not clear what mechanisms were responsible for the removal of this remaining CO2. From a biological point of view, we find that the duration of liquid water habitats on early Mars exceeds the upper limit on the time required for the origin of life on Mars.

This paper describes the hospital planning model developed by the North Eastern Metropolitan Region of the Health Department Victoria to forecast acute public hospital bed-day requirements in the Region. Three age-specific variables: population; separation rate; and length of stay have been used to estimate the level of demand for hospital services. The model also delineates services delivered on a same day or long stay basis. The application of the model to three local government areas demonstrates the importance of population growth and ageing on the type and level of hospital services required and the implications thereof for service delivery and the physical configuration of hospitals.

In this study, a site-specific immunoconjugate, designated CYT-356, of the prostate-reactive monoclonal antibody 7E11-C5 was characterized by immunohistological methods for reactivity with normal and neoplastic human tissues. In addition, CYT-356 labeled with 111In was assessed by in vivo imaging and pharmacokinetic studies for localization to human tumor xenografts in nude mice. The native antibody and the site-specific immunoconjugate exhibited similar patterns of reactivity with normal human tissues. Although the majority of tissues tested were negative, weak reactivity with cardiac muscle, proximal kidney tubules, and sweat glands was observed. Positive staining of normal prostate epithelial cells and glandular lumina and strong reactivity with a subset of skeletal muscle cells were also observed. CYT-356 reacted with 100% of prostate tumors examined but was negative on a variety of other neoplasms. Following i.v. administration, CYT-356-111In rapidly localized to and imaged LNCaP human prostate adenocarcinoma xenografts in nude mice, reaching maximal levels of about 30% of injected dose/g of tumor within 3 days. No unusual localization was seen to any nontumor tissue or organ; the level of radioactivity in the normal tissues and organs was at or below that seen in the blood. The localization to xenografts was antigen specific and the accessible binding sites in 100-200-mg tumors appeared to be saturated at an antibody dose between 10 and 100 micrograms. These findings suggest that the CYT-356 immunoconjugate may be useful in the diagnosis and therapy of prostate cancer.

Information regarding the presence of the glyoxylate cycle in chick liver was sought. This metabolic pathway has long been thought to be absent from vertebrate tissues. Previous studies in other tissues have shown that, when present, this pathway is sensitive to vitamin-D. Thus, the effect of long-term vitamin-D deficiency and subsequent vitamin-D replacement on liver structure was studied by light microscopy. In addition, specific biochemical assays for the presence of glyoxylate cycle enzymes were performed. Light microscopy of lipid extracted tissues, light microscopic histochemistry, and quantitative histochemistry showed that the hepatocytes from vitamin-D-deficient animals contained primarily lipid. Hepatocytes from normal and vitamin-D-replete livers contained primarily carbohydrate as judged by their staining with periodic acid-Schiff (PAS). Also, malate synthase positive peroxisomes were seen in hepatocytes from normal and vitamin-D-treated chicks. Structures positive for this glyoxylate cycle enzyme were rarely seen in the hepatocytes from vitamin-D-deficient animals. Biochemical analyses showed the presence of the two unique glyoxylate cycle enzymes, isocitrate lyase and malate synthase, in chick hepatocytes. The activity of these enzymes was markedly increased in the vitamin-D-replete livers. In addition, chick hepatocytes demonstrated the capacity to oxidize fatty acid in the presence of cyanide. This activity, which is characteristic of peroxisomal B-oxidation rather than mitochondrial, was stimulated by vitamin-D treatment. Lastly, incubation of chick liver in the presence of a fatty acid substrate (palmitate) led to higher tissue glycogen content. The latter was further increased in liver from vitamin-D-replete animals. These data show the presence of glyoxylate cycle enzymes in a higher vertebrate and indicate that this tissue is endowed with the capacity to convert lipid to carbohydrate.

The presence of secretory protein-I (SP-I) or chromogranin A (CGA) in granules isolated from the granular cells of the amphibian urinary bladder epithelium was investigated using ultraimmunohistochemistry. Granules were isolated by cell fractionation using Percoll density gradients. SP-I was isolated and purified from bovine parathyroid glands. Antibodies were raised in rabbits and purified by affinity chromatography. Ultraimmunocytochemistry, employing the avidin-biotin-peroxidase (ABC-complex) procedure, was used to localize SP-I on thin sections of isolated granules. About 27% of the granules from control (-ADH) cells were SP-I+, while 51% of the granules fractionated from hormone treated (+ADH) cells were positive for this protein (p less than 0.0001). Accordingly, granules from ADH-treated cells also showed a significant (p less than 0.0001) increase in total protein.