A phase II trial of bevacizumab and rucaparib in recurrent carcinoma of the cervix or endometrium.

OBJECTIVE: The aim of this study was to examine the tolerability and efficacy of combination bevacizumab rucaparib therapy in patients with recurrent cervical or endometrial cancer. PATIENTS & METHODS: Thirty-three patients with recurrent cervical or endometrial cancer were enrolled. Patients were required to have tumor progression after first line treatment for metastatic, or recurrent disease. Rucaparib was given at 600 mg BID twice daily for each 21-day cycle. Bevacizumab was given at 15 mg/kg on day 1 of each 21-day cycle. The primary endpoint was efficacy as determined by objective response rate or 6-month progression free survival. RESULTS: Of the 33 patients enrolled, 28 were evaluable. Patients with endometrial cancer had a response rate of 17% while patients with cervical cancer had a response rate of 14%. Median progression free survival was 3.8 months (95% C·I 2.5 to 5.7 months), and median overall survival was 10.1 months (95% C·I 7.0 to 15.1 months). Patients with ARID1A mutations displayed a better response rate (33%) and 6-month progression free survival (PFS6) rate (67%) than the entire study population. Observed toxicity was similar to that of previous studies with bevacizumab and rucaparib. CONCLUSIONS: The combination of bevacizumab with rucaparib did not show significantly increased anti-tumor activity in all patients with recurrent cervical or endometrial cancer. However, patients with ARID1A mutations had a higher response rate and PFS6 suggesting this subgroup may benefit from the combination of bevacizumab and rucaparib. Further study is needed to confirm this observation. No new safety signals were seen.

PRPs localized to the middle lamellae are required for cortical tissue integrity in Medicago truncatula roots.

KEY MESSAGE: A family of repetitive proline-rich proteins interact with acidic pectins and play distinct roles in legume root cell walls affecting cortical and vascular structure. A proline-rich protein (PRP) family, composed of tandemly repeated Pro-Hyp-Val-X-Lys pentapeptide motifs, is found primarily in the Leguminosae. Four distinct size classes within this family are encoded by seven tightly linked genes: MtPRP1, MtPRP2 and MtPRP3, and four nearly identical MtPRP4 genes. Promoter fusions to ß-glucuronidase showed strong expression in the stele of hairy roots for all 4 PRP genes tested, with additional expression in the cortex for PRP1, PRP2 and PRP4. All except MtPRP4 are strongly expressed in non-tumorous roots, and secreted and ionically bound to root cell walls. These PRPs are absent from root epidermal cell walls, and PRP accumulation is highly localized within the walls of root cortical and vascular tissues. Within xylem tissue, PRPs are deposited in secondary thickenings where it is spatially exclusive to lignin. In newly differentiating xylem, PRPs are deposited in the regularly spaced paired-pits and pit membranes that hydraulically connect neighboring xylem elements. Hairpin-RNA knock-down constructs reducing PRP expression in Medicago truncatula hairy root tumors disrupted cortical and vascular patterning. Immunoblots showed that the knockdown tumors had potentially compensating increases in the non-targeted PRPs, all of which cross-react with the anti-PRP antibodies. However, PRP3 knockdown differed from knockdown of PRP1 and PRP2 in that it greatly reduced viability of hairy root tumors. We hypothesize that repetitive PRPs interact with acidic pectins to form block-copolymer gels that can play distinct roles in legume root cell walls.

Deep learning can see the unseeable: predicting molecular markers from MRI of brain gliomas.

This paper describes state-of-the-art methods for molecular biomarker prediction utilising magnetic resonance imaging. This review paper covers both classical machine learning approaches and deep learning approaches to identifying the predictive features and to perform the actual prediction. In particular, there have been substantial advances in recent years in predicting molecular markers for diffuse gliomas. There are few examples of molecular marker prediction for other brain tumours. Deep learning has contributed significantly to these advances, but suffers from challenges in identifying the features used to make predictions. Tools to better identify and understand those features represent an important area of active research.

ABI5-binding proteins (AFPs) alter transcription of ABA-induced genes via a variety of interactions with chromatin modifiers.

KEY MESSAGE: Overexpression of ABI5/ABF binding proteins (AFPs) results in extreme ABA resistance of seeds via multiple mechanisms repressing ABA response, including interactions with histone deacetylases and the co-repressor TOPLESS. Several ABI5/ABF binding proteins (AFPs) inhibit ABA response, resulting in extreme ABA resistance in transgenic Arabidopsis overexpression lines, but their mechanism of action has remained obscure. By analogy to the related Novel Interactor of JAZ (NINJA) protein, it was suggested that the AFPs interact with the co-repressor TOPLESS to inhibit ABA-regulated gene expression. This study shows that the AFPs that inhibit ABA response have intrinsic repressor activity in a heterologous system, which does not depend on the domain involved in the interaction with TOPLESS. This domain is also not essential for repressing ABA response in transgenic plants, but does contribute to stronger ABA resistance. Additional interactions between some AFPs and histone deacetylase subunits were observed in yeast two-hybrid and bimolecular fluorescence assays, consistent with a more direct mechanism of AFP-mediated repression of gene expression. Chemical inhibition of histone deacetylase activity by trichostatin A suppressed AFP effects on a small fraction of the ABI5-regulated genes tested. Collectively, these results suggest that the AFPs participate in multiple mechanisms modulating ABA response, including both TOPLESS-dependent and -independent chromatin modification.

The RSNA Image Sharing Network.

In the era of health information exchanges, there are trade-offs to consider when sharing a patient's medical record among all providers that a patient might choose. Exchange among in-network partners on the same electronic medical records (EMR) and other integrated information systems is trivial. The patient identifier is common, as are the relevant departmental systems, to all providers. Difficulties arise when patient records including images (and reports) must be shared among different networks and even with the patients themselves. The National Institutes of Health (NIH) challenged Radiological Society of North America (RSNA) to develop a transport method that could supersede the need for physical media (for patients or other providers), replace point-to-point private networks among providers, and enable image exchange on an ad hoc basis between arbitrary health networks without long legal delays. In concert with the evolving US health care paradigm, patient engagement was to be fundamental. With Integrating Healthcare Enterprise's (IHE's) help, the challenge has been met with an operational system.

Generative Adversarial Networks for Brain MRI Synthesis: Impact of Training Set Size on Clinical Application.

We evaluated the impact of training set size on generative adversarial networks (GANs) to synthesize brain MRI sequences. We compared three sets of GANs trained to generate pre-contrast T1 (gT1) from post-contrast T1 and FLAIR (gFLAIR) from T2. The baseline models were trained on 135 cases; for this study, we used the same model architecture but a larger cohort of 1251 cases and two stopping rules, an early checkpoint (early models) and one after 50 epochs (late models). We tested all models on an independent dataset of 485 newly diagnosed gliomas. We compared the generated MRIs with the original ones using the structural similarity index (SSI) and mean squared error (MSE). We simulated scenarios where either the original T1, FLAIR, or both were missing and used their synthesized version as inputs for a segmentation model with the original post-contrast T1 and T2. We compared the segmentations using the dice similarity coefficient (DSC) for the contrast-enhancing area, non-enhancing area, and the whole lesion. For the baseline, early, and late models on the test set, for the gT1, median SSI was .957, .918, and .947; median MSE was .006, .014, and .008. For the gFLAIR, median SSI was .924, .908, and .915; median MSE was .016, .016, and .019. The range DSC was .625-.955, .420-.952, and .610-.954. Overall, GANs trained on a relatively small cohort performed similarly to those trained on a cohort ten times larger, making them a viable option for rare diseases or institutions with limited resources.

Direct interactions of ABA-insensitive(ABI)-clade protein phosphatase(PP)2Cs with calcium-dependent protein kinases and ABA response element-binding bZIPs may contribute to turning off ABA response.

Abscisic acid (ABA) signaling via the pyrabactin-resistant and related (PYR/PYL/RCAR) receptors begins with ABA-dependent inactivation of the ABA-insensitive(ABI)-clade protein phosphatases(PP)2Cs, thereby permitting phosphorylation and activation of the Snf1-related (SnRK)2 clade of protein kinases, and activation of their downstream targets such as ABA-response element binding basic leucine zipper (bZIP) transcription factors (ABF/AREB/ABI5 clade). Several of these are also activated by calcium-dependent protein kinases such as CPK11. Turning off ABA response requires turnover and/or inactivation of these transcription factors, which could result from their dephosphorylation. To address the hypothesis that the ABI-clade PP2Cs regulate the bZIPs directly, in addition to their indirect effects via SnRKs, we have assayed interactions between multiple members of the ABF/AREB clade and the PP2Cs by yeast two-hybrid, in vitro phosphatase, and bimolecular fluorescence complementation assays. In addition, we have expanded the list of documented specific interactions among these bZIP proteins and the kinases that could activate them and found that some PP2Cs can also interact directly with CPK11. These studies support specific interactions among kinases, phosphatases and transcription factors that are co-expressed in early seedling development.

Isolation of a novel adenovirus from Rousettus leschenaultii bats from India.

Surveillance work was initiated to study the presence of highly infectious diseases like Ebola-Reston, Marburg, Nipah and other possible viruses that are known to be found in the bat species and responsible for causing diseases in humans. A novel adenovirus was isolated from a common species of fruit bat (Rousettus leschenaultii) captured in Maharashtra State, India. Partial sequence analysis of the DNA polymerase gene shows this isolate to be a newly recognized member of the genus Mastadenovirus (family Adenoviridae), approximately 20% divergent at the nucleotide level from Japanese BatAdV, its closest known relative.

Preserved anatomical bypasses predict variance in language functions after stroke.

The severity of post-stroke aphasia is related to damage to white matter connections. However, neural signaling can route not only through direct connections, but also along multi-step network paths. When brain networks are damaged by stroke, paths can bypass around the damage to restore communication. The shortest network paths between regions could be the most efficient routes for mediating bypasses. We examined how shortest-path bypasses after left hemisphere strokes were related to language performance. Regions within and outside of the canonical language network could be important in aphasia recovery. Therefore, we innovated methods to measure the influence of bypasses in the whole brain. Distinguishing bypasses from all residual shortest paths is difficult without pre-stroke imaging. We identified bypasses by finding shortest paths in subjects with stroke that were longer than the most reliably observed connections in age-matched control networks. We tested whether features of those bypasses predicted scores in four orthogonal dimensions of language performance derived from a principal components analysis of a battery of language tasks. The features were the length of each bypass in steps, and how many bypasses overlapped on each individual direct connection. We related these bypass features to language factors using support vector regression, a technique that extracts robust relationships in high-dimensional data analysis. The support vector regression parameters were tuned using grid-search cross-validation. We discovered that the length of bypasses reliably predicted variance in lexical production (R2 = .576) and auditory comprehension scores (R2 = .164). Bypass overlaps reliably predicted variance in Lexical Production scores (R2 = .247). The predictive elongation features revealed that bypass efficiency along the dorsal stream and ventral stream were most related to Lexical Production and Auditory Comprehension, respectively. Among the predictive bypass overlaps, increased bypass routing through the right hemisphere putamen was negatively related to lexical production ability.

Visualization of 3D osteon morphology by synchrotron radiation micro-CT.

Cortical bone histology has been the subject of scientific inquiry since the advent of the earliest microscopes. Histology - literally the study of tissue - is a field nearly synonymous with 2D thin sections. That said, progressive developments in high-resolution X-ray imaging are enabling 3D visualization to reach ever smaller structures. Micro-computed tomography (micro-CT), employing conventional X-ray sources, has become the gold standard for 3D analysis of trabecular bone and is capable of detecting the structure of vascular (osteonal) porosity in cortical bone. To date, however, direct 3D visualization of secondary osteons has eluded micro-CT based upon absorption-derived contrast. Synchrotron radiation micro-CT, through greater image quality, resolution and alternative contrast mechanisms (e.g. phase contrast), holds great potential for non-destructive 3D visualization of secondary osteons. Our objective was to demonstrate this potential and to discuss areas of bone research that can be advanced through the application of this approach. We imaged human mid-femoral cortical bone specimens derived from a 20-year-old male (Melbourne Femur Collection) at the Advanced Photon Source synchrotron (Chicago, IL, USA) using the 2BM beam line. A 60-mm distance between the target and the detector was employed to enhance visualization of internal structures through propagation phase contrast. Scan times were 1 h and images were acquired with 1.4-µm nominal isotropic resolution. Computer-aided manual segmentation and volumetric 3D rendering were employed to visualize secondary osteons and porous structures, respectively. Osteonal borders were evident via two contrast mechanisms. First, relatively new (hypomineralized) osteons were evident due to differences in X-ray attenuation relative to the surrounding bone. Second, osteon boundaries (cement lines) were delineated by phase contrast. Phase contrast also enabled the detection of soft tissue remnants within the vascular pores. The ability to discern osteon boundaries in conjunction with vascular and cellular porosity revealed a number of secondary osteon morphologies and provided a unique 3D perspective of the superimposition of secondary osteons on existing structures. Improvements in resolution and optimization of the propagation phase contrast promise to provide further improvements in structural detail in the future.

Multi-institutional Outcomes and Associations After Excision and Primary Anastomosis for Radiotherapy-associated Bulbomembranous Urethral Stenoses Following Prostate Cancer Treatment.

OBJECTIVE: To evaluate the outcomes of excision and primary anastomosis (EPA) for radiation-associated bulbomembranous stenoses using a multi-institutional analysis. The treatment of radiation-associated urethral stenosis is typically complex owing to the adverse impact of radiation on adjacent tissue. METHODS: An IRB-approved multi-institutional retrospective review was performed on patients who underwent EPA for bulbomembranous urethral stenosis following prostate radiotherapy. Preoperative patient demographics, operative technique, and postoperative outcomes were abstracted from 1/2007-6/2018. Success was defined as voiding per urethra without the need for endoscopic treatment and a minimum follow-up of 12 months. RESULTS: One hundred and thirty-seven patients from 10 centers met study criteria with a mean age of 69.3 years (50-86), stenosis length of 2.3 cm (1-5) and an 86.9% (119/137) success rate at a mean follow-up 32.3 months (12-118). Univariate Cox regression analysis identified increasing patient age (P = .02), stricture length (P <.0001) and combined modality radiotherapy (P = .004) as factors associated with stricture recurrence while body mass index (P = .79), diabetes (P = .93), smoking (P = .62), failed endoscopic treatment (P = .08) and gracilis muscle use (P = .25) were not. On multivariate analysis, increasing patient age (H.R.1.09, 95%CI 1.01-1.16; P = .02) and stenosis length (H.R.2.62, 95%CI 1.49-4.60; P = .001) remained associated with recurrence. Subsequent artificial urinary sphincter was performed in 30 men (21.9%), of which 25 required a transcorporal cuff and 5 developed cuff erosion. CONCLUSIONS: EPA for radiation-associated urethral stenosis effectively provides unobstructed instrumentation-free voiding. However, increasing stenosis length and age are independently associated with surgical failure. Patients should be counseled that further surgery for incontinence may be necessary.

Immunochemical localization and amino acid sequences of crossreactive epitopes within the group A streptococcal M6 protein.

mAbs 10A11, 10B6, and 10F5, raised against the native group A streptococcal M6 protein, were examined for their crossreactivity with non-laboratory passaged clinical isolates, representing 58 M serotypes, by bacterial dot blot immunoassay. mAb 10A11 crossreacted with 9, mAb 10B6 with 30, and mAb 10F5 with 30 different non-M6 serotypes. To identify the epitopes for these antibodies, the native M6 protein was cleaved with pepsin or staphylococcal V8 protease. Resultant peptides were purified by HPLC, examined for binding to crossreactive mAbs in ELISA, and reactive peptides were subjected to amino acid sequence analysis. Peptides were aligned with the amino acid sequence of the entire M6 protein predicted by the DNA sequence of the M6 gene. Competitive inhibition studies using peptides synthesized on the basis of peptide and DNA sequences, in concert with selective blocking of amino acid residues, allowed for the further identification and placement of these crossreactive epitopes within the M6 molecule. The 10A11 epitope was located within the six amino acid residues at position 134-139, which repeat at positions 159-164 and 184-189 within the variable amino terminal half of the native molecule. The conserved 10B6 and 10F5 epitopes were positioned within a 15-amino-acid span at position 275-289, with the possibility that either epitope could have been repeated at residues 239-247. Chemical modification of amino acids within this sequence aided in the differentiation of these two epitopes. Such studies should aid in the recognition of a sequence(s) common to a greater number of M serotypes, which may be useful for future vaccine development or group A streptococcal identification.

Evidence-based algorithm for the management of acute traumatic retrobulbar haemorrhage.

Retrobulbar haemorrhage (RBH) is a potentially blinding consequence of craniofacial trauma, but timely ophthalmic evaluation is difficult to obtain in some settings and clear standards for canthotomy/cantholysis are lacking. We have sought to develop an algorithm to identify vision-threatening traumatic RBH that requires emergent decompression. We retrospectively reviewed 42 consecutive consultations for RBH at a level-one trauma centre. Charts and imaging studies were analysed with attention to mechanism of injury, comorbid trauma, and ophthalmic findings. A total of 22 eyes were observed without intervention, 13 were treated pharmacologically, and seven by emergent canthotomy/cantholysis. No differences in standard trauma metrics were found among these groups. Lid oedema, ecchymosis, chemosis, subconjunctival haemorrhage, and ocular motility also failed to correlate with a need for surgical intervention. "Tight" eyelids (p<0.001), unilateral proptosis (p<0.001), and relative afferent pupillary defect (RAPD; p=0.029), however, all related to a need for canthotomy/cantholysis (Fisher's exact test). Tenting of the globe, which was the only radiographic finding to predict the need for surgery, was seen in just two of the seven cases that required decompression. Many of the traditionally emphasised clinical signs therefore fail to identify cases of RBH that require decompression. Our data support a simple three-factor decision tool. These are: relative proptosis, eyelids that are difficult to open with finger pressure, and presence of an RAPD in the traumatised eye. If all three are noted or if the patient has proptosis and tight lids in the absence of a large preseptal haematoma, he/she is likely to need surgical decompression. Tenting of the globe on computed tomography (CT), while a relatively rare finding, should also alert the physician of the need for intervention.

Imaging of remyelination and neuronal health.

Remyelination of axons that have been demyelinated due to multiple sclerosis (MS) may be a critical step in restoring the damaged axons and reversing the disease process. While it is possible to establish the presence of remyelination with microscopy of tissue samples, it is important to have noninvasive or minimally invasive methods to measure remyelination in living animals and humans. Such tools are critical to establishing the efficacy of agents purported to promote or enhance remyelination. This chapter reviews the technology of imaging of the brain, its application to MS, and the current state of imaging techniques for measuring remyelination and the health of the associated neurons in the setting of MS.

Murray fracture zone: westward extension.

The Murray Fracture Zone is one of the principal east-west rifts in the crust of the northeast Pacific basin. As judged by bathymetric and magnetic surveys, the Murray approaches the Hawaiian Archipelago as a well-defined zone of ridges and troughs accompanied by strong, linear magnetic anomalies. It loses its topographic expression on encountering the Hawaiian Arch but can be traced magnetically to its intersection with the Hawaiian Ridge in the vicinity of Laysan Island (near 172 degrees W). All evidence tends to discount a previously suggested genetic relation between the Murray Fracture Zone and the Necker Ridge.

Clinical and radiographic spectrum of pathologically confirmed tumefactive multiple sclerosis.

Atypical imaging features of multiple sclerosis lesions include size >2 cm, mass effect, oedema and/or ring enhancement. This constellation is often referred to as 'tumefactive multiple sclerosis'. Previous series emphasize their unifocal and clinically isolated nature, however, evolution of these lesions is not well defined. Biopsy may be required for diagnosis. We describe clinical and radiographic features in 168 patients with biopsy confirmed CNS inflammatory demyelinating disease (IDD). Lesions were analysed on pre- and post-biopsy magnetic resonance imaging (MRI) for location, size, mass effect/oedema, enhancement, multifocality and fulfilment of Barkhof criteria. Clinical data were correlated to MRI. Female to male ratio was 1.2 : 1, median age at onset, 37 years, duration between symptom onset and biopsy, 7.1 weeks and total disease duration, 3.9 years. Clinical course prior to biopsy was a first neurological event in 61%, relapsing-remitting in 29% and progressive in 4%. Presentations were typically polysymptomatic, with motor, cognitive and sensory symptoms predominating. Aphasia, agnosia, seizures and visual field defects were observed. At follow-up, 70% developed definite multiple sclerosis, and 14% had an isolated demyelinating syndrome. Median time to second attack was 4.8 years, and median EDSS at follow-up was 3.0. Multiple lesions were present in 70% on pre-biopsy MRI, and in 83% by last MRI, with Barkhof criteria fulfilled in 46% prior to biopsy and 55% by follow-up. Only 17% of cases remained unifocal. Median largest lesion size on T2-weighted images was 4 cm (range 0.5-12), with a discernible size of 2.1 cm (range 0.5-7.5). Biopsied lesions demonstrated mass effect in 45% and oedema in 77%. A strong association was found between lesion size, and presence of mass effect and/or oedema (P < 0.001). Ring enhancement was frequent. Most tumefactive features did not correlate with gender, course or diagnosis. Although lesion size >5 cm was associated with a slightly higher EDSS at last follow-up, long-term prognosis in patients with disease duration >10 years was better (EDSS 1.5) compared with a population-based multiple sclerosis cohort matched for disease duration (EDSS 3.5; P < 0.001). Given the retrospective nature of the study, the precise reason for biopsy could not always be determined. This study underscores the diagnostically challenging nature of CNS IDDs that present with atypical clinical or radiographic features. Most have multifocal disease at onset, and develop RRMS by follow-up. Although increased awareness of this broad spectrum may obviate need for biopsy in many circumstances, an important role for diagnostic brain biopsy may be required in some cases.

Does having a rotator cuff repair prior to reverse total shoulder arthroplasty influence the outcome?

AIMS: The number of rotator cuff repairs that are undertaken is increasing. Reverse shoulder arthroplasty (RSA) is the procedure of choice for patients with rotator cuff arthropathy. We sought to determine whether patients who underwent rotator cuff repair and subsequent RSA had different outcomes compared with a matched control group who underwent RSA without a previous rotator cuff repair. PATIENTS AND METHODS: All patients with a history of rotator cuff repair who underwent RSA between 2000 and 2015 with a minimum follow-up of two years were eligible for inclusion as the study group. Outcomes, including the American Shoulder and Elbow Surgeons (ASES) scores, were compared with a matched control group of patients who underwent RSA without having previously undergone rotator cuff repair. RESULTS: The study group included 45 patients. Their mean age was 69 years (sd 8.6) and 27 patients (60%) were women. The mean ASES score improved from 43.1 to 76.6 two years postoperatively, and to 66.9 five years postoperatively. There was no significant difference between the outcomes at two years in the two groups (all p ≥ 0.05), although there was significantly more improvement in ASES scores in the control group (44.5 vs 33.4; p = 0.01). However, there was no significant difference between ASES scores at two and five years when baseline ASES scores were matched in the two groups (p = 0.42 at two years; p = 0.35 at five years). CONCLUSION: Significant improvements in ASES scores were seen following RSA in patients who had previously undergone rotator cuff repair. They had higher baseline ASES scores than those who had not previously undergone this surgery. However, there was no significant difference in outcomes between the two groups, two years postoperatively. Previous rotator cuff repair does not appear to affect the early outcome after RSA adversely.

Multisite Concordance of DSC-MRI Analysis for Brain Tumors: Results of a National Cancer Institute Quantitative Imaging Network Collaborative Project.

BACKGROUND AND PURPOSE: Standard assessment criteria for brain tumors that only include anatomic imaging continue to be insufficient. While numerous studies have demonstrated the value of DSC-MR imaging perfusion metrics for this purpose, they have not been incorporated due to a lack of confidence in the consistency of DSC-MR imaging metrics across sites and platforms. This study addresses this limitation with a comparison of multisite/multiplatform analyses of shared DSC-MR imaging datasets of patients with brain tumors. MATERIALS AND METHODS: DSC-MR imaging data were collected after a preload and during a bolus injection of gadolinium contrast agent using a gradient recalled-echo-EPI sequence (TE/TR = 30/1200 ms; flip angle = 72°). Forty-nine low-grade (n = 13) and high-grade (n = 36) glioma datasets were uploaded to The Cancer Imaging Archive. Datasets included a predetermined arterial input function, enhancing tumor ROIs, and ROIs necessary to create normalized relative CBV and CBF maps. Seven sites computed 20 different perfusion metrics. Pair-wise agreement among sites was assessed with the Lin concordance correlation coefficient. Distinction of low- from high-grade tumors was evaluated with the Wilcoxon rank sum test followed by receiver operating characteristic analysis to identify the optimal thresholds based on sensitivity and specificity. RESULTS: For normalized relative CBV and normalized CBF, 93% and 94% of entries showed good or excellent cross-site agreement (0.8 ≤ Lin concordance correlation coefficient ≤ 1.0). All metrics could distinguish low- from high-grade tumors. Optimum thresholds were determined for pooled data (normalized relative CBV = 1.4, sensitivity/specificity = 90%:77%; normalized CBF = 1.58, sensitivity/specificity = 86%:77%). CONCLUSIONS: By means of DSC-MR imaging data obtained after a preload of contrast agent, substantial consistency resulted across sites for brain tumor perfusion metrics with a common threshold discoverable for distinguishing low- from high-grade tumors.

Anaphylatoxin-induced histamine release with human leukocytes: studies of C3a leukocyte binding and histamine release.

Purified human C3a and synthetic COOH-terminal peptides of C3a, i.e., a pentapeptide, Leu-Gly-Leu-Ala-Arg (5R), and an octapeptide, Ala-Ala-Ala-Leu-Gly-Leu-Ala-Arg (8R) induced histamine release from human basophil granulocytes. On a molar basis, 5R was one-tenth and 8R was one-fifth as active as C3a in causing histamine release. It was found that 125I-C3a binds to whole leukocytes, interacting with both mononuclear cells and neutrophils and the binding was inhibited by preincubation of cells with unlabeled C3a, but not by C5a. 5R and 8R also inhibited the binding of 125I-C3a to the cells. However, on a molar basis, 2,000 times more 8R or 6,000 times more 5R is required for 50% inhibition of 125I-C3a binding as compared with native C3a. Autoradiography of cells using 125I-C3a and 125I-C5a showed preferential binding of 125I-C3a to eosinophils and basophils, whereas 125I-C5a binds primarily to neutrophils and eosinophils and to a lesser extent to basophils. The preferential binding of C3a and C5a to different cell types may herald significance related to their physiological functions.

Infiltrative chordoid meningioma of the pineal region: a study of 2 cases.

OBJECTIVE: Meningiomas involving the pineal region are rare. Herein we describe two cases of chordoid meningioma with histologic evidence of pineal gland infiltration. MATERIALS AND METHODS: Clinical histories were abstracted from chart review and consultation letters. HE-stained slides were reviewed in both cases. Selected immunohistochemical stains were performed. RESULTS: the patients included a 44-year-old male and a 37-year-old female who presented with symptoms of intracranial tumor referable to the pineal region. On magnetic resonance imaging (MRI), both lesions demonstrated heterogeneous contrast enhancement. Histologically, the tumors were characterized by strands and cords ofmeningothelial cells arranged in a mucinous stroma. In addition, obvious meningothelial cytology as well as focal osseous metaplasia (Case 1), and transitional histology (Case 2) were also noted. Tumor cells demonstrated EMA and focal S100 protein immunoreactivity, but lacked cytokeratin AE1/AE3 and glial fibrillary acidic protein (GFAP) staining. Synaptophysin and neurofilament protein highlighted the overrun pineal gland parenchyma. MIB1-proliferative index was 8.4 and 20.1%, respectively. CONCLUSIONS: Chordoid meningioma, although rare, may occur in the pineal region. The differential diagnosis of this meningioma subtype in this location is discussed.