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J B Rubin

Publications and source records attributed to J B Rubin.

At least 19 recordsLinked to original sources
PubMed1992

A domain substitution procedure and its use to analyze voltage dependence of homotypic gap junctions formed by connexins 26 and 32.

We have developed a procedure for the replacement of defined domains with specified domains from other proteins that we used to examine the molecular basis for the differences in voltage-dependent gating between connexins 26 (Cx26) and 32 (Cx32). This technique does not depend on sequence homology between the domains to be exchanged or the presence of restriction endonuclease sites. Rather, it makes use of a PCR strategy to create an adhesive "band-aid" that directs the annealing of the amplified sequence to the correct location in the recipient clone. With this technique we created a series of chimeras involving the replacement of topologically defined protein domains of Cx32 with the corresponding sequences of Cx26. We focused on domains that are predicted to line the gap junction channel as we expect that a component of the voltage-sensing mechanism resides there. Differences between Cx26 and Cx32 in the sequences of their first and second extracellular loops, the cytoplasmic loop, and the third transmembrane domain did not account for the difference in their calculated gating charges. Shifts along the voltage axis in the steady-state conductance-voltage relations of the chimeric connexins were produced by replacement of the first extracellular loop or the cytoplasmic loop and the amino-terminal half of the third transmembrane domain. These data suggest that the voltage-sensing mechanism arises from the interaction of domains lining the aqueous channel and domains deeper in the channel wall.

Amino Acid Sequence↗
PubMed1992

Molecular analysis of voltage dependence of heterotypic gap junctions formed by connexins 26 and 32.

Heterotypic gap junctions formed by pairing Xenopus oocytes expressing hemichannels formed of Cx32 with those expressing hemichannels formed of Cx26 displayed novel transjunctional voltage (Vj) dependence not predicted by the behavior of these connexins in homotypic configurations. Rectification of initial and steady-state currents was observed. Relative positivity and negativity on the Cx26 side of the junction resulted in increased and decreased initial conductance (gj0), respectively. Only relative positivity on the Cx26 decreased steady-state conductance (gj infinity). This behavior suggested that interactions between hemichannels influences gap junction gating. The role of the first extracellular loop (E1) in these interactions was examined by pairing Cx32 and Cx26 with a chimeric connexin in which Cx32 E1 was replaced with Cx26 E1 (Cx32*26E1). Both junctions rectified with gj0/Vj relations that were less steep than that observed for Cx32/Cx26. Decreases in gj infinity occurred for either polarity Vj in the Cx32/Cx32*26E1 junction. Mutation of two amino acids in Cx26 E1 increased the steepness of both the gj0/Vj and gj infinity/Vj relations. These data demonstrate that fast rectification can arise from mismatched E1 domains and that E1 may contribute to the voltage sensing mechanisms underlying both fast and slow Vj-dependent processes.

Amino Acid Sequence↗
PubMed1989

Short TR, variable flip angle, gradient echo scans of the cervical spine: comparison of 2DFT and 3DFT techniques.

A prospective study of 16 patients was performed to compare quantitatively a contiguous single slice 2DFT version with a 3DFT version of a short TR, variable flip angle, gradient echo (GRASS) pulse sequence. The 3DFT GRASS scans had higher signal-to-noise ratios (SNR) of cord and CSF compared to the single slice 2DFT GRASS scans. The 3DFT GRASS scans, however, had lower CSF-cord and CSF-disc contrast than the single slice 2DFT version. The 3DFT GRASS sequence demonstrated comparable contrast only on the end slices of an imaging volume suggesting influence of an entry phenomenon. The lower CSF-cord and CSF-disc contrast of the 3DFT GRASS technique diminished its usefulness in the diagnosis of cervical disc disease compared to the single slice 2DFT GRASS technique. Two different slice thicknesses (3 mm and 5 mm) were investigated with the 2DFT GRASS technique and found to be comparable although the 3 mm scans had sharper disc and dural margins because of less partial volume artifact.

Cervical Vertebrae↗
PubMed1988

Specific trophic factor-receptor interactions. Key selective elements in brain development and "regeneration".

An hypothesis is presented which emphasizes the key role of specific trophic factor-receptor interactions in the development of the brain. We postulate that very early in development neurons become dependent on external factors (mainly neuropeptides) for guidance and survival. These requirements are the key to the selection process which results in the creation of a functional nervous system. These specific localized trophic factor requirements are postulated to persist throughout life. Disruptions in specific trophic factor-receptor systems are postulated to be responsible for a variety of age-related neurodegenerative diseases. The implications of recent animal and human transplant experiments in the context of the theoretical framework discussed above are profound. It would appear that the mature mammalian brain possesses an exquisite ability to regenerate specific connections to replace those lost due to death or injury to nerve cells. Unfortunately, it does not contain a population of undifferentiated stem cells to supply the necessary healthy neurons. The reason for this appears obvious based on the theoretical considerations given above, that the specific trophic factor-receptor interactions needed to produce a functional brain circuitry are necessarily stringently selective. Therefore, a significant stem cell population does not survive. However, if an appropriate stem cell population, ie, a fetal transplant, is provided, the brain will "heal itself" according to the program outlined above. In the future it may be technically feasible to perform genetic testing of newborns to determine to which genetic neurological diseases they are susceptible and at an appropriate time provide the appropriate fetal transplant. Obviously, society will have to deal with the profound ethical questions this technology will raise.

Animals↗
PubMed1988

Cervical spine: MR imaging with a partial flip angle, gradient-refocused pulse sequence. Part I. General considerations and disk disease.

A magnetic resonance imaging pulse sequence with a short repetition time (TR), short echo time (TE), partial flip angle, and gradient refocused echo was evaluated for the detection of cervical disk disease in a prospective study of 90 patients. These parameters were manipulated to adjust signal-to-noise ratio (S/N) and contrast: flip angle (3 degrees-18 degrees), TR (22-60 msec), and TE (12.5-25 msec). Flip angle had the greatest effect on S/N and contrast; its effect differed between axial and sagittal imaging. Cerebrospinal fluid S/N reached a peak at a smaller flip angle in sagittal imaging than in axial imaging. The useful range of flip angles depended on TR. Increasing TR had minimal direct effect on S/N or contrast, but because a longer TR allowed the use of larger flip angles for both axial and sagittal imaging, higher S/N could be achieved with similar contrast. This effect of increasing TR had to be balanced against increased imaging time and increased probability of motion artifact. Increasing TE decreased S/N, increased contrast, and increased magnetic susceptibility artifacts. For the diagnosis of cervical disk disease, the best sequence appears to be one with a very short TR, short TE, and small flip angles within a narrow range.

Cervical Vertebrae↗
PubMed1988

Cervical spine: MR imaging with a partial flip angle, gradient-refocused pulse sequence. Part II. Spinal cord disease.

A magnetic resonance imaging pulse sequence (GRASS) with a short repetition time (TR), short echo time (TE), partial flip angle, and gradient refocused echo was prospectively evaluated for the detection of cervical cord disease that caused minimal or no cord enlargement in eight patients. Sagittal T2-weighted, cerebrospinal fluid (CSF)-gated images and sagittal and axial GRASS images were obtained in all patients. The following GRASS parameters were manipulated to determine their effect on signal-to-noise ratio (S/N) and contrast: flip angle (4 degrees-18 degrees), TR (22-50 msec), and TE (12.5-25 msec). Flip angle had the greatest effect on S/N and contrast. There were no differences between axial and sagittal imaging for the spinal cord or lesion. However, because the signal intensity of CSF did differ on sagittal and axial images and because this influenced the conspicuity of lesions, there was a difference in the useful flip angle range for axial and sagittal imaging. No one set of imaging parameters was clearly superior, and in all patients, the gated image was superior to the sagittal GRASS image in lesion detection. GRASS images should be used in the axial plane primarily to confirm spinal cord disease detected on sagittal CSF-gated images. For this, a balanced approach is suggested (TR = 40 msec, TE = 20 msec, with flip angles of 4 degrees-6 degrees for sagittal and 6 degrees-8 degrees for axial imaging).

Humans↗
PubMed1988

Lumbar spine: motion compensation for cerebrospinal fluid on MR imaging.

To determine whether the motion of cerebrospinal fluid (CSF) in the lumbar spine degrades T2-weighted magnetic resonance (MR) images, a spine phantom, three healthy volunteers, and a prospective series of 20 patients suspected of having lumbar spine disease underwent MR imaging with and without motion-compensation techniques. In the phantom, pulsation amplitudes as low as 3 mm (within the physiologic range of human lumbar CSF motion) reduced image quality on conventional images but not on motion-compensated images. Similar findings were observed in two volunteers and 11 patients. The magnitude of the artifacts was variable; they could impair visualization of the conus, decrease contrast or reduce the sharpness of the CSF-thecal sac interface, and cause focal regions of reduced CSF signal intensity adjacent to bulging disks. Image quality was most improved when peripheral gating was combined with even-echo rephasing. In the patient group, the use of motion-compensation techniques increased the CSF signal-to-noise ratio by an average of 29% (P less than .01); this resulted in improved contrast between the conus and extradural structures. The data suggest that CSF motion compensation is clinically useful during T2-weighted MR imaging of the lumbar spine.

Adult↗
PubMed1987

Receptor-mediated transcytosis of transferrin across the blood-brain barrier.

The perfusion of rat brain with 125I-transferrin resulted in a receptor-mediated uptake of transferrin into the endothelium of the blood-brain barrier followed by its detection in the brain. During a pulse-chase experiment, 125I-transferrin accumulated in the endothelial cells during the pulse, with a decrease of this intraendothelial radioactivity during the chase associated with a concomitant increase in the nonvascular elements of the brain. The receptor-mediated movement of transferrin across the blood-brain barrier suggests that the brain may derive its iron through the transcytosis of iron-loaded transferrin across the brain microvasculature. We discuss the likelihood that aluminum and other potentially toxic heavy metals, which also bind tightly to transferrin, may enter the brain by this pathway. We also discuss the possibility that other large molecules including neuroactive peptides and neurotrophic viruses may enter the brain through a similar receptor-mediated, vesicular transcytotic route.

Animals↗
PubMed1987

Use of cerebrospinal fluid gating to improve T2-weighted images. Part I. The spinal cord.

Ungated and gated magnetic resonance images of the spinal cord acquired with the use of long repetition times (TRs) and long echo-delay times (TEs) were compared in 21 studies performed on a 1.5-T system. Both normal and abnormal spinal cord conditions were compared. All images were acquired in an identical fashion except that ungated studies had TRs of 2,000 or 2,500 msec, whereas in gated studies, TR was determined by the patient's heart rate. The effective TR of images gated to the cerebrospinal fluid (CSF) fell primarily in the range of 1,500-1,800 msec. Gating was accomplished using a peripheral pulse. Three image parameters were assessed: signal-to-noise ratio, object contrast, and resolving power. For each parameter, in both normal and abnormal spinal cords, the CSF-gated studies proved superior by eliminating spatially mismapped signal intensity from pulsatile CSF.

Cerebrospinal Fluid↗
PubMed1987

Use of cerebrospinal fluid gating to improve T2-weighted images. Part II. Temporal lobes, basal ganglia, and brain stem.

Ungated and gated magnetic resonance images of the temporal lobes, basal ganglia, and brain stem acquired with the use of long repetition times (TRs) and long echo-delay times (TEs), were compared quantitatively. Twenty-five pairs of images obtained on a 1.5-T system were evaluated. Ungated images (TR = 2,000 msec, TE = 80 msec) were acquired in the same manner as gated images except for TR, which, for gated studies, was determined by a patient's heart rate and generally fell into the 1,500-1,800-msec range. Three image parameters were assessed: signal-to-noise ratio (S/N), object contrast, and resolving power. In both normal and abnormal brain tissue, gated images were superior to ungated images in object contrast and resolving power and equivalent in S/N. More so than in comparable studies of the spinal cord, ungated studies were susceptible to both false-positive and false-negative interpretations. As in spinal cord studies, the major benefit of gating was the elimination of phase shift images arising from basal cisterns and the third ventricle.

Basal Ganglia↗
PubMed1987

Cervical spine MR imaging: generating high-signal CSF in sagittal and axial images.

Three magnetic resonance (MR) imaging techniques were compared as to their ability to generate images with high-signal cerebrospinal fluid (CSF) to provide a high-contrast CSF-dura interface. The three techniques were CSF gating to the peripheral pulse, selective saturation recovery with gradient refocusing (SSRGR), and gradient recalled acquisition in the steady state (GRASS). In sagittal views of the cervical spine, CSF gating proved to be a reliable technique for producing images with uniform high-signal CSF in a single-section or multi-section mode. In axial views, SSRGR and GRASS techniques were more consistent than CSF gating in producing high-signal CSF images, especially in a multisection mode. Although axial image quality was nearly equivalent for SSRGR and GRASS techniques, the latter was clinically more efficient because of shorter imaging times. These methods of imaging in the cervical spine yield sufficient CSF-dura contrast and spatial resolution to be of use in the diagnosis of cervical disk disease.

Cerebrospinal Fluid↗
PubMed1987

Optimizing conventional MR imaging of the spine.

With the use of conventional spin-echo pulse sequences with a long repetition time (TR), the echo time (TE) and the number of echoes were varied to minimize cerebrospinal fluid (CSF) flow artifacts in a spine phantom and in cervical spines of three volunteers. The following echo trains were compared in both axial and sagittal planes with a TR of 2,000 msec: TE of 25, 80 msec ("asymmetric"); TE of 40, 80 msec ("symmetric long TE"); and TE of 20, 40, 60, and 80 msec ("symmetric short TE"). Variable degrees of even-echo rephasing of CSF flow artifacts were observed during sagittal but not axial imaging, depending on the echo train used. Even-echo rephasing was most complete with the symmetric short-TE echo train, less complete with the symmetric long-TE echo train, and absent with the asymmetric echo train. Switching the orientation of the phase and frequency encoding gradients and slightly modifying TR on the basis of the heart rate further improved image quality. The results suggest that a symmetric short-TE echo train may be used to provide velocity compensation (similar to that observed with rephasing gradients) on even echoes of conventional spin-echo pulse sequences during spine imaging.

Cerebrospinal Fluid↗
PubMed1987

CSF-gated MR imaging of the spine: theory and clinical implementation.

A spine phantom and cervical spines of seven volunteers were studied with cerebrospinal fluid (CSF)-gated magnetic resonance imaging to optimize acquisition factors reducing CSF flow artifacts. Peripheral gating was performed with either an infrared reflectance photoplethysmograph or peripheral arterial Doppler signal. The effects of effective repetition time, echo train, trigger delay, number of sections, and imaging plane on image quality were evaluated. Gated imaging of oscillatory CSF motion simulated constant-velocity flow and reduced CSF flow artifacts caused by cardiac-dependent temporal phase-shift effects. Velocity compensation on sagittal even-echo images with a symmetric short-echo time echo train reduced the remaining CSF flow artifacts caused by spatial phase-shift effects. Overall gated imaging time was not increased compared with nongated imaging and was reduced when improved image quality permitted the use of fewer excitations. These results suggest that the combination of CSF gating and flow compensation is clinically useful and efficient because it improves image quality without prolonging imaging time.

Cerebrospinal Fluid↗
PubMed1987

Potential false-negative MR images of the thoracic spine in disk disease with switching of phase- and frequency-encoding gradients.

Two patients with thoracic disk protrusion were evaluated with magnetic resonance imaging. A T1-weighted spin-echo sequence was used, with and without switching of the phase- and frequency-encoding gradients. Both disks were well delineated when the frequency-encoding gradient was parallel to the spinal axis. When the gradients were switched (with the phase-encoding gradient parallel to the spinal axis), both herniated disks were partially obscured by a posteriorly displaced fat signal from marrow, caused by a chemical shift artifact. In addition, the anterior subarachnoid space appeared falsely narrowed, and the cerebrospinal fluid (CSF) signal intensity was increased, which reduced the CSF-cord contrast. These findings suggest that switching the orientation of the frequency- and phase-encoding gradients may result in false-negative T1-weighted sagittal images of the thoracic spine.

Adult↗
PubMed1987

Dyke award. Imaging of spinal CSF pulsation by 2DFT MR: significance during clinical imaging.

Understanding the MR appearance of spinal CSF is important in interpreting clinical spine images because the diagnosis of spinal pathology requires an accurate delineation of spinal CSF from spinal cord and thecal sac. During conventional 2DFT MR imaging of the spine, CSF pulsation caused two interdependent flow phenomena, signal loss and phase-shift images. Signal loss was observed as decreased signal intensity arising from pulsatile spinal CSF. Phase-shift images were observed as signal intensity arising from and morphologically identical to the spinal subarachnoid space but symmetrically displaced from it along the phase-encoding axis of MR images, either added to or subtracted from stationary signal intensity. These phenomena were common, occurring in most cervical and thoracic long-TR images. Both phenomena were less apparent in the lumbar region in most cases. CSF pulsation flow phenomena decreased CSF-spinal cord and CSF-thecal sac conspicuity, thereby obscuring normal and pathologic anatomy and, at times, simulating pathology. The areas of signal loss showed variable but characteristic patterns in the cervical and thoracic spine corresponding to regions of greatest flow. Signal loss in the axial plane was more pronounced when thin slices were used. Phase-shift images degraded overall image quality secondary to spatial mismapping of spinal CSF signal intensity. With the use of CSF gating, both signal loss and phase-shift images were eliminated. Understanding these features will be important in the accurate interpretation of MR spine images because analysis of CSF pulsation flow phenomena provides physiologic and pathologic information, and awareness of their existence avoids diagnostic confusion.

Adolescent↗
PubMed1987

Dyke award. Harmonic modulation of proton MR precessional phase by pulsatile motion: origin of spinal CSF flow phenomena.

The effects of pulsatile motion on MR imaging of spinal CSF were quantitatively evaluated with a spine phantom that simulated spinal CSF pulsation. Two fundamental interdependent pulsation flow phenomena were observed: variable reductions in signal intensity of pulsatile CSF (signal loss) and spatial mismapping of this signal beyond the confines of the subarachnoid space (phase-shift images). Phase-shift images were observed as multiple regions of signal intensity conforming morphologically to the subarachnoid space but displaced symmetrically from it along the phase-encoding axis, either added to or subtracted from stationary signal intensity. Both CSF pulsation flow phenomena occurred secondary to harmonic modulation of proton precessional phase (temporal phase shift) by the unique pulsatile motion of spinal CSF when the repetition time was not an integral multiple of the pulsation period. Each flow phenomenon was analyzed with the spine phantom independently to control individual imaging and physiologic parameters including imaging plane, repetition time, echo time, slice thickness, number of echoes, number of excitations, CSF pulsation amplitude, and CSF pulsation period. In the axial plane, signal loss was present on both first- and second-echo images and was more pronounced with larger pulsation amplitudes and smaller slice thicknesses. A quantitative relationship between these two parameters allowed the prediction of CSF pulsation amplitude when the slice thickness was known and the CSF signal intensity was measured. In the sagittal plane, signal loss was present on first-echo images, was more pronounced with larger pulsation amplitudes, and underwent incomplete even-echo rephasing on second-echo images. Phase-shift images were influenced by the relationship between repetition time and CSF pulsation period. They were partly eliminated on sagittal but not on axial second-echo images because of incomplete even-echo rephasing. Both signal loss and phase-shift images were completely eliminated with CSF gating or pseudogating, indicating the rationale for gating during clinical spinal MR. The clinical significance of these findings is that awareness of the existence of spinal CSF pulsation flow phenomena avoids diagnostic confusion, whereas understanding their etiology provides a rational approach, such as CSF gating, to eliminate them.

Cerebrospinal Fluid↗
PubMed1987

CSF pulsations within nonneoplastic spinal cord cysts.

Because of its sensitivity to fluid motion, MR imaging was used to investigate fluid dynamics in syringomyelia. Three major findings characterized syringomyelia: pulsatile fluid in cysts, nonpulsatile fluid in cysts, and damaged cord tissue. The fluid in preoperative syrinx cavities pulsated in a fashion similar to subarachnoid CSF. Pulsation was more prominent in large cysts but was also seen in small cysts. Nonpulsatile cysts were generally of smaller diameter, were shorter in length, and often were single; they could, however, coexist with pulsatile cysts. Nonpulsatile cysts had etiologies similar to those of pulsatile cysts: Chiari malformation, trauma, and unknown. Damaged cord, characterized by abnormal high signal on T2-weighted sequences, was seen in 15 of 16 patients and could be either focal or diffuse but was always adjacent to syrinx cavities. Postsurgical MR scans had a lower incidence of pulsatile cysts. In five patients with both pre- and postoperative MR scans, shunting of the cyst reduced the size of the pulsating cyst (two patients) or reduced the size of the cyst and eliminated pulsation altogether (three patients). Axial, T2-weighted images are recommended in the investigation of spinal cord cysts to determine the presence or absence of pulsatile fluid. The presence of pulsation indicates a nonneoplastic cyst. The absence or reduction of CSF pulsation may prove to be a valuable indicator of the success of a shunting procedure.

Cerebrospinal Fluid↗