rab3A attachment to the synaptic vesicle membrane mediated by a conserved polyisoprenylated carboxy-terminal sequence.

rab3A is a small neuronal GTP-binding protein specifically localized to synaptic vesicles. Membrane-bound rab3A behaves like an intrinsic membrane protein in vitro, but reversibly dissociates from synaptic vesicles after exocytosis in vivo. Here we demonstrate that rab3A is attached to synaptic vesicle membranes by a carboxy-terminal Cys-X-Cys sequence that is posttranslationally modified. This modification is inhibited by compactin in a mevalonate-dependent manner, suggesting that the Cys-X-Cys sequence represents a novel polyisoprenylation sequence. Isolation of a rab3 homolog from D. melanogaster reveals high evolutionary conservation of rab3A, including its carboxy-terminal Cys-X-Cys sequence. The posttranslational modifications of soluble and membrane-bound rab3A are biochemically different, but both require the carboxy-terminal Cys-X-Cys sequence and are faithfully reproduced in nonneuronal cells. Our results suggest that the carboxy-terminal Cys-X-Cys sequence of rab3A is polyisoprenylated and is used as its regulatable membrane anchor. Furthermore, the hydrophobic modification of rab3A and its correct intracellular targeting to synaptic vesicles are independent, presumably consecutive events.

Radiation protection standards: their evolution from science to philosophy.

The concept of applying constraints on individual sources to a small fraction of the public dose limit has been deemed inappropriate when shielding the medical X-ray sources. This represents a broad-based consensus of medical physics and radiological societies in the United States, and the report series on the shielding design for medical X-ray sources (including dental, X-ray imaging and therapeutic X ray) from the National Council on Radiation Protection and Measurements (NCRP) utilises 1 mSv y(-1) as a source control limit. In the present study, the rationale for such a conclusion is discussed, and a somewhat critical look at the current model of radiation protection of the public is made.

Histological demonstration of copper and copper-associated protein in chronic liver diseases.

Liver copper concentrations in percutaneous biopsy specimens were measured by neutron activation analysis and compared with histological staining for copper by rubeanic acid and rhodanine, and with copper-associated protein stained by orcein. Liver copper concentrations were elevated in 31 of 35 biopsies from patients with primary biliary cirrhosis (PBC), and discrimination between normal and elevated liver copper was correct in 32 of the 35 biopsies by staining with rubeanic acid, and 31 of the 35 by staining with rhodanine. Orcein staining of copper-associated protein was positive in 33 of the 35 biopsies. All 17 biopsy specimens from patients with Wilson's disease had high liver copper concentrations, but only nine had positive staining for copper, and six were orcein positive. Similarly, histological stains gave little indication of the liver copper concentrations in tissue from 16 patients with chronic active hepatitis. Staining of liver sections can be useful in detecting elevation of liver copper in PBC, but not in Wilson's disease, where the absolute concentration must be measured. Excess copper appears to accumulate in the liver in different chemical forms in PBC and Wilson's disease.

Absence of exercise-induced MRI enhancement of skeletal muscle in McArdle's disease.

To assess the role of glycogenolysis in mediating exercise-induced increases in muscle water as monitored by changes in muscle proton relaxation times on magnetic resonance imaging (MRI) and cross-sectional area (CSA), five patients with myophosphorylase deficiency (MPD) were compared with seven controls. Absolute and relative work loads were matched during ischemic handgrip and graded cycling, respectively. Relaxation times of active muscle did not increase after handgrip in MPD (T1: 1 +/- 14%, P greater than 0.1; T2: 4 +/- 4%, P greater than 0.1) but did in controls (T1: 59 +/- 30%, P less than 0.005; T2: 26 +/- 9%, P less than 0.005). The volume of exercised muscles, estimated by CSA, increased in both groups after handgrip (controls: 13.8 +/- 3.5%, n = 7, P less than 0.0001; MPD: 7.5 +/- 1.5%, n = 4, P less than 0.005), but the change was greater in controls (P less than 0.02). Ischemic handgrip in controls resulted in a large increase in finger flexor signal intensity (SI) on short tau-inversion recovery images (25 +/- 7%, n = 3; P less than 0.005 compared with preexercise) and a further increase with subsequent reflow (43 +/- 11%, n = 3; P less than 0.001 compared with rest); in MPD, SI did not increase. The ratio of active to inactive muscle SI did not increase from rest to maximal cycle exercise in MPD (0 +/- 20%, n = 2, P greater than 0.1) but did in normals (73 +/- 36%, n = 3; P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Determination of diagnostic x-ray spectra with characteristic radiation using attenuation analysis.

An analytical method to compute x-ray spectra from attenuation data utilizing the Laplace transformation has been extended to include characteristic radiation. It is based on an a priori technique of determining the ratio of characteristic radiation exposure to the total radiation exposure in diagnostic spectra. The technique is shown to produce characteristic intensities in good agreement with experimentally determined values.

A Laplace transform pair model for spectral reconstruction.

A four-parameter Laplace transform pair model, which accurately reconstructs an experimental bremsstrahlung spectrum from attenuation data, is presented. Computed spectral values with both aluminum and copper attenuators generally agree with experimental 70-kVp data to better than 2%. Reconstructed spectra at other kVp's also show good agreement with published data.

Computer-assisted quality assurance for radiographic equipment.

A quality assurance procedure which includes a computer program has been implemented to facilitate measurement of some of the parameters normally tested on diagnostic radiographic equipment. These include: reproducibility of output, linearity of mA settings, filtration, kVp calibration, timer error, SID indication, light field--x-ray field coincidence and effective focal spot size. The user may omit those sections which are not applicable to his needs. Full use is made of the data reducing the number of field measurements needed.

On the measurement of half-value layer in film-screen mammography.

Sources of variations in the measurement of half-value layer (HVL) in film-screen mammography are evaluated. Two principal sources are the energy responses of ionization chambers and the elemental compositions of the 1100 aluminum-alloy attenuation materials. Methods in measuring the thickness of attenuation materials are also an important potential source of error. These factors as well as the influence of geometry of measurement, position of measurement in the field, and precision of radiation output are examined. Recommendations for consistency in measurement are provided.

Laplace reconstruction of experimental diagnostic x-ray spectra.

This paper displays the results of a blind study used to determine the capability of a Laplace transform pair model to accurately reconstruct diagnostic x-ray spectra from experimental attenuation data. Spectra reconstructed from attenuation measurements are compared to experimental spectra obtained on the same unit using an intrinsic germanium spectrometer system. The results show that when pure attenuation materials are used, good agreement is obtained between the experimental and computed spectra. If an alloy attenuator like 1100 aluminum is used, the proportion of contaminants must be included in the Laplace formulation for accurate reconstruction.

Multivariate analysis of TLD orientation effects.

The effect of orientation on extruded thermoluminescent dosimeters has been investigated. TLD's placed on the surface and within a phantom were exposed separately to five diagnostic beam qualities and to 60Co gamma rays. The resulting data were subjected to analysis of variance and examined for significant correlations. The response of dosimeters on the phantom surface varied with orientation and was energy dependent. In the phantom and with 60Co, no orientation effects were observed.

Dosimeter placement in the Rando phantom.

Each section of the Alderson Rando phantom contains a tissue-equivalent plastic coating layer approximately 2 mm thick, applied to both faces. This compensates for material removed in the sawing process. Conventional use of thermoluminescent dosimeters positions them totally or partially within the coating layer. Analysis shows that, in the lung region, dosimeters placed in this layer received a dose averaging 39% lower than those placed at midsection. Where bony structures interfere, some dosimeters in the coating layer received an 18% higher dose than those at midsection. Therefore, positioning dosimeters at the center of a section is recommended.

Application of a Laplace transform pair model for high-energy x-ray spectral reconstruction.

A Laplace transform pair model, previously shown to accurately reconstruct x-ray spectra at diagnostic energies, has been applied to megavoltage energy beams. The inverse Laplace transforms of 2-, 6-, and 25-MV attenuation curves were evaluated to determine the energy spectra of these beams. The 2-MV data indicate that the model can reliably reconstruct spectra in the low megavoltage range. Experimental limitations in acquiring the 6-MV transmission data demonstrate the sensitivity of the model to systematic experimental error. The 25-MV data result in a physically realistic approximation of the present spectrum.

Attenuation properties of diagnostic x-ray shielding materials.

Single- and three-phase broad-beam x-ray attenuation data have been obtained using lead, steel, plate glass, gypsum wallboard, lead acrylic, and wood. Tube voltages of 50, 70, 100, 125, and 150 kVp were employed and the resulting curves were compared to transmission data found in the literature. To simplify computation of barrier requirements, all data sets were parametrized by nonlinear least-squares fit to a previously described mathematical model. High attenuation half value layers and the lead equivalence of the alternate materials were also determined.

A MRI gradient waveform model for automated sequence calibration.

In order to set up magnetic resonance imaging (MRI) procedures of arbitrary voxel dimensions, slice orientation, and sequence timing in a reasonable time, some form of automatic gradient pulse calibration is required. One such method, involving simulation of gradient waveforms, is presented. Waveforms are modeled based on measurements of the step response. The model used divides each transition into three time regions: a "start" region in the first 0.3 ms, a "slew" region, and a "tail" region representing decay of the eddy current compensation error. In the "slew" region, the time derivative of the gradient, G' (t), is expressed as a function of G(t). The first two regions are nonlinear with respect to demand. The mean error in the simulated gradient is generally less than 0.04 mT m-1 in spin echo sequences. Image signal/noise ratios resulting from sequences calibrated using the model are within 5% of those of empirically calibrated sequences.

A modified x-ray spectra reconstruction technique.

We have previously reported on a four-parameter Laplace transform pair model that accurately reconstructs x-ray spectra from attenuation data. However, for some spectra, the model exhibits non-physical characteristics at the higher x-ray energies. This results when one of the fitted parameters, v, is less than or equal to 0.6. Simply limiting the parameter to values greater than 0.6 produces an unsatisfactory result. It is shown that improved accuracy is obtained when the model is applied to a more filtered segment of the attenuation curve. The resulting spectrum is satisfactory for the more filtered beam. One can then reliably construct the original spectrum by mathematically correcting for the additional filtration.

Low resolution spin echo: a simple timesaving technique for MRI liver exams.

MR evaluation of the liver at mid-field strength requires relatively lengthy T2-weighted sequences (T2W) for differentiation of benign cavernous hemangiomas from malignant lesions. A short duration T2W, which maintains standard signal-to-noise ratio and also contrast relationships, can be easily implemented by increasing the pixel size in the phase-encoding direction (thus reducing spatial resolution) and proportionally decreasing the number of phase-encoding steps in the matrix (thus reducing acquisition time). Blinded interpretations of a quick (4 min), low resolution (3.4 mm x 1.7 mm pixel) T2W sequence (matrix 64 x 256, FOV 21.7 cm phase x 43.5 cm frequency) were compared to the 17 min standard resolution (1.7 mm x 1.7 mm) T2W sequence (256 x 256 matrix, FOV 43 x 43 cm) in 25 patients suspected of having liver metastasis. Lesions felt to be cavernous hemangiomas showed a 100% (24/24) agreement for interpreter "A" and 96% (22/23) agreement for interpreter "B" when 4 min low resolution T2W was compared to the standard 17 min sequence. Sensitivity (for all types of lesions) of the low resolution T2W sequence ranged from 100% (31/31) for interpreter "A" to 80% (28/35) for interpreter "B." Missed lesions (interpreter "B") were either partially obscured by excessive fat (wrap around) (N = 4), less than 1 cm in size (N = 2), or degraded by motion artifact (N = 1). Thus in many situations low resolution T2 may provide a substantial timesaving alternative to standard T2W particularly where T2W is used primarily for lesion classification in normal sized patients.

A separation and purification procedure for [14C] di-2-ethylhexyl phthalate in fish.

A procedure utilizing the reverse isotope dilution analysis is presented for the determination of di-2-ethylhexyl phthalate (DEHP) and total metabolites in tissues of fish and water samples. This procedure offers several advantages: it eliminates laborious and expensive use of column chromatography and identification by gas chromatography/mass spectrometry analysis; it does not require quantitative separation; it selectively removes fish lipids by partitioning across a hexane/acetonitrile system; it uses an internal standard, di-pentylphthalate, for the gas-liquid chromatographic analysis; and it overcomes interference from background DEHP.

Protecting patients by training physicians in fluoroscopic radiation management.

During the past 15 years, developments in x-ray technologies have substantially enhanced the ability of practitioners to treat patients using fluoroscopically guided interventional techniques. However, many of these procedures require a greater use of fluoroscopy and serial imaging (cine). This has increased the potential for radiation-induced dermatitis, epilation, and severe radiation-induced burns to patients. It has also increased the potential for radiation injury and radiation-induced cancer in personnel. This work will describe a number of the cases that have appeared in the literature and current recommendations and credentialing requirements of various organizations whose members use fluoroscopy. Finally, a program for implementing training of physicians in radiation management as a means of reducing the risk of injury to patients and personnel is recommended.

History of the shielding of diagnostic x-ray facilities.

The results of inadequate protection of radiation workers against the harmful effects of diagnostic x-rays became appallingly apparent shortly after the turn of this century. After these effects (which included erythema, malignancy, and even death) became widely known, efforts were begun to implement recommendations to reduce the hazards to radiologic workers and members of the general public. This work will trace the development of diagnostic radiation shielding standards from the earliest days to the present time.

Diagnostic X-ray shielding design based on an empirical model of photon attenuation.

A series of nomograms that simplify determination of diagnostic X-ray shielding requirements with lead are presented. All recommendations of the NCRP, except that to "add one half value layer" in determining secondary barriers, were followed in the production of these curves. For secondary barriers, the shielding required to reduce the weekly exposure to the applicable MPD has been determined. This eliminates the over-shielding inherent in the "add one HVL" approximation and allows a variety of more cost effective materials to be considered for secondary barriers.