Positional cloning of the gene for X-linked retinitis pigmentosa 3: homology with the guanine-nucleotide-exchange factor RCC1

The gene for retinitis pigmentosa 3 (RP3), the most frequent form of X- linked RP (XLRP), has been mapped previously to a chromosome interval of less than 1000 kbp between the DXS1110 marker and the OTC locus at Xp21.1-p11.4. Employing a novel technique, YAC Representation Hybridization (YRH)', we have recently identified a small XLRP associated microdeletion in this interval, as well as several putative exons including the 3' end of a gene that was truncated by the deletion. cDNA library screening and sequencing of a cosmid centromeric to the deletion has now enabled us to identify numerous additional exons and to detect several point mutations in patients with XLRP. The predicted gene product shows homology to RCC1, the guanine-nucleotide- exchange factor (GEF) of the Ras-like GTPase Ran. Our findings suggest that we have cloned the long-sought RP3 gene, and that it may encode the GEF of a retina-specific GTP-binding protein.      

Short-Ti inversion-recovery pulse sequence: analysis and initial experience in cancer imaging

Inversion recovery (IR), commonly considered a pulse sequence capable of producing T1-weighted images with excellent display of normal anatomy, is versatile: The null point and peak time provide a useful, succinct summary of the properties of IR and its capacity for producing both T1- and T2-weighted images. Shortening of the inversion time (TI) and creation of a short-TI inversion-recovery (STIR) pulse sequence increases sensitivity to malignancy and other abnormalities by making the effects of prolonged T1 and T2 on signal intensity additive and by nulling the signal from fat. The authors examined over 300 patients with various malignancies and compared STIR images with T1- and T2-weighted images obtained at 0.5 T. In 43 cases, signal-difference-to-noise ratios (SD/Ns) were calculated between tumor, fat, and muscle. In general, STIR images demonstrated tumor as a conspicuously high-intensity area in a background of muted, discernible anatomic detail. The good contrast achieved with STIR sequences between tumor and fat (SD/N = 18.1) and tumor and muscle (SD/N = 12.9) consolidated into a single image the information contained separately on T1- and T2-weighted images, which facilitates efficient detection and localization of malignancy.     

The varied semiology of seizures in the context of small anterior temporal encephaloceles

Aims. Small encephaloceles of the anterior temporal pole have been increasingly recognised as an underlying epileptogenic substrate in patients with medically refractory epilepsy. The current report aims to expand on the current knowledge by emphasising that seizure semiology in such patients can vary significantly. Methods. Patients were selected from an epilepsy surgery database between 2012 and 2017. Results. Of the 143 patients who underwent epilepsy surgery, six patients had a temporal encephalocele. Four of these patients had stereo-EEG implantation. Of the four patients studied, each had a seizure semiology discordant with an ictal focus in the temporal lobe. Intracranial EEG assessment demonstrated, irrespective of this semiology, seizures originated from the anterior temporal pole. Seizures were observed to rapidly propagate to the orbitofrontal cortex, insula, temporo-occipital junction, and posterior language regions. Engagement of the mesial temporal structures could occur early or late, however, a good surgical outcome was achieved following a focused lesionectomy in either situation. Conclusion. The major finding was that seizures arising from anterior temporal encephaloceles can have an extra-temporal semiology. The varied clinical semiology and the rapid propagation to seemingly distant cortical regions could be explained by the connectivity of the anterior temporal lobe.     

Inactivation of purified human alpha 2-antiplasmin and purified human C1 inhibitor by synthetic fibrinolytic agents

3-Hydroxypropyl flufenamide (Flu-HPA) is one of a series of flufenamic acid derivatives that enhances blood clot lysis in vitro. Studies of possible mechanisms of action of Flu-HPA were undertaken. The profibrinolytic activity of Flu-HPA in clot lysis assays was found to be dependent on plasminogen. The influence of Flu-HPA on the ability of purified alpha 2-antiplasmin to inhibit purified plasmin was studied. Plasmin activity was determined using 125I-fibrin plates or the spectrophotometric tripeptide substrate, Val-Leu-Lys-paranitroanilide. At Flu-HPA concentrations greater than 1 mM, the inhibitory activity of alpha 2-antiplasmin was abolished in a time-dependent and concentration- dependent manner. The influence of Flu-HPA on the ability of purified Cl inhibitor to inhibit purified plasma kallikrein and beta-Factor XIIa was also studied. Cl inhibitor activity was abolished by Flu-HPA at concentrations greater than 2 mM. Notably, Flu-HPA up to 60 mM did not affect the amidolytic activities of plasmin, kallikrein, or beta-Factor XIIa. Flu-HPA did not release enzyme activity from preformed complexes of either alpha 2-antiplasmin and plasmin of Cl inhibitor and kallikrein. A water-soluble derivative of flufenamic acid, N-flufenamyl- glutamic acid, also inactivated alpha 2-antiplasm and Cl inhibitor. This inactivation was shown to be reversible. These results indicate that synthetic fibrinolytic compounds such as flufenamic acid derivatives may promote fibrinolysis by directly inactivating alpha 2- antiplasmin and Cl inhibitor.     

Evaluation of [18F]-JNJ-64326067-AAA tau PET tracer in humans

The [¹⁸F]-JNJ-64326067-AAA ([¹⁸F]-JNJ-067) tau tracer was evaluated in healthy older controls (HCs), mild cognitive impairment (MCI), Alzheimer’s disease (AD), and progressive supranuclear palsy (PSP) participants. Seventeen subjects (4 HCs, 5 MCIs, 5 ADs, and 3 PSPs) received a [¹¹C]-PIB amyloid PET scan, and a tau [¹⁸F]-JNJ-067 PET scan 0-90 minutes post-injection. Only MCIs and ADs were amyloid positive. The simplified reference tissue model, Logan graphical analysis distribution volume ratio, and SUVR were evaluated for quantification. The [¹⁸F]-JNJ-067 tau signal relative to the reference region continued to increase to 90 min, indicating the tracer had not reached steady state. There was no significant difference in any bilateral ROIs for MCIs or PSPs relative to HCs; AD participants showed elevated tracer relative to controls in most cortical ROIs (P < 0.05). Only AD participants showed elevated retention in the entorhinal cortex. There was off-target signal in the putamen, pallidum, thalamus, midbrain, superior cerebellar gray, and white matter. [¹⁸F]-JNJ-067 significantly correlated (p < 0.05) with Mini-Mental State Exam in entorhinal cortex and temporal meta regions. There is clear binding of [¹⁸F]-JNJ-067 in AD participants. Lack of binding in HCs, MCIs and PSPs suggests [¹⁸F]-JNJ-067 may not bind to low levels of AD-related tau or 4 R tau.     

Septo-optic dysplasia: MR imaging

Septo-optic dysplasia is the diagnosis when optic nerve hypoplasia is seen in conjunction with dysgenesis of the septum pellucidum. Nearly two-thirds of these patients have hypothalamic-pituitary dysfunction, and half have schizencephaly. The disorder is difficult to classify because of the diversity of clinical and pathologic manifestations. Magnetic resonance images of 11 patients with clinical and radiographic evidence of septo-optic dysplasia were reviewed retrospectively. The "syndrome" appears to include two subsets of patients whose abnormalities have different embryogenesis and neuropathologic findings. The existence of these two subsets helps to explain the diversity of the clinical and radiologic findings.     

Normal deposition of brain iron in childhood and adolescence: MR imaging at 1.5 T

Magnetic resonance (MR) images of the brain in 285 patients between the ages of 2 and 25 years were retrospectively studied to determine the appearance of brain iron accumulation. The globus pallidus, red nucleus, substantia nigra, and dentate nucleus were evaluated with long TR/TE (repetition time/echo time) spin-echo sequences and staged. All four regions in most patients were initially hyperintense compared with white matter (stage I) before becoming isointense (stage II) and subsequently hypointense (stage III). The globus pallidus was the first to reach stage III, the red nucleus and substantia nigra were next, and the dentate nucleus was last. In general, decreased signal intensity (stage III) was not seen in these regions in patients less than 10 years old; in most patients it was seen by age 25 years. The dentate nucleus decreased in signal intensity more slowly and inconsistently; only one-third of patients had reached stage III by age 25 years. The temporal sequence of normal iron deposition as detected with MR imaging is helpful not only in the diagnosis of known iron-deposition diseases but also in the detection of iron-related pathologic changes.     

Shoulder joint: arthrographic CT and long-term follow-up, with surgical correlation

One hundred two computed tomographic (CT) arthrograms of the shoulder were retrospectively reviewed and compared with conventional double-contrast arthrograms from 101 patients (24 females and 77 males aged 9-70 years). One- to 4-year follow-up was obtained in 84 patients, 40 of whom underwent open-shoulder surgery or arthroscopy. Morphology of the normal portions of each labrum was categorized according to length, width, and tip shape. Correlation between morphology and age was weak, but abnormal labra were more common in younger patients. Conventional radiography was more accurate for detecting bony glenoid margin fractures, but CT was more accurate for detecting Hill-Sach fractures. CT was also more reliable than conventional arthrography in the detection of rotator cuff tears. Hence, few if any conventional radiographs are necessary between contrast material injection and CT imaging. A reduction in the number of images obtained will result in decreased radiation dose, less cost, and shorter examination time without loss of diagnostic accuracy.