Pattern Of Tissue Injury Research Articles

Depth of Hemoclip Attachment, Tissue Injury, & Fibrosis After Hemostasis of Bleeding Acute Canine Gastric Ulcers in a Randomized Controlled Study

Thermal probes (e.g. Multipolar probe-MPEC) have been used for about 3 decades to effectively seal vessels in bleeding non-variceal UGI lesions. However, thermal hemostasis can enlarge ulcers & cause complications especially with bleeding acute ulcers (AU). Now different hemoclips (HC) are marketed for endoscopic treatment (Rx) but their tissue injury patterns & depth of attachment have not been reported. Whether HC's accelerate or delay ulcer healing vs. MPEC is unknown. Purposes: In a randomized controlled study (RCS) of HC's & MPEC: 1) to compare initial hemostasis & HC closure of AU's & retention rates of HC's.

Naive and Memory T Cells Induce Different Types of Graft-versus-Host Disease

The goal of this study was to compare the ability of donor naive and alloantigen-primed effector memory T cells to induce graft-vs-host disease after bone marrow transplantation in MHC-mismatched irradiated host mice. Purified CD4(+) naive (CD62L(high)CD44(low)) T cells and CD4(+) effector memory (CD62L(low)CD44(high)) T cells obtained from unprimed donors and donors primed to host alloantigens, respectively, were injected into host mice, and the rapidity, severity, and pattern of tissue injury of graft-vs-host disease was assessed. Unexpectedly, the naive T cells induced a more acute and severe colitis than the primed memory cells. Whereas the naive T cells expressing CD62L and CCR7 lymph node homing receptors vigorously expanded in mesenteric lymph nodes and colon by day 6 after transplantation, the primed memory T cells without these receptors had 20- to 100-fold lower accumulation at this early time point. These differences were reflected in the significantly more rapid decline in survival and weight loss induced by naive T cells. The primed memory T cells had a greater capacity to induce chronic colitis and liver injury and secrete IL-2 and IFN-gamma in response to alloantigenic stimulation compared with memory T cells from unprimed donors. Nevertheless, the expected increase in potency as compared with naive T cells was not observed due to differences in the pattern and kinetics of tissue injury.

A Comparison of Joint Loading Profiles During Windmill and Overhead Throwing

Differences in arm position when loads are maximal during overhead and windmill pitching, may have effects on tissue stress and injury patterns. PURPOSE: To compare the magnitude and joint position when loads are maximal on the elbow and shoulder during overhead and windmill throwing. METHODS: Distractive forces, joint moments and position data were analyzed in ten experienced female softball pitchers. An 8-camera motion analysis system collected data at 240 Hz. Kinetic data were normalized for ball speed using the ratio of average windmill to overhead style ball speed (1.14 = 57 mph/50 mph). Data from the average of three fast-ball strikes were analyzed by repeated measures one-way ANOVA and Tukey's post-hoc analysis. RESULTS: The table below provides means (standard deviations) for peak shoulder and elbow loads and the corresponding joint position. Positions are relative to a reference position (elbow: straight; shoulder: arm directed laterally with the cubital fossa directed superior).TableCONCLUSIONS: Our findings suggest that the windmill style may produce less harmful stress on the stabilizers of the medial elbow and anterior/inferior shoulder. Since pitchers of both throwing styles are routinely injuried, over-utilization of may play a key role in the pathogenesis of injuries found in windmill pitchers.

Cortical, subcortical and spinal alterations in neuroimmunological diseases

Inflammatory and immune mediated diseases of the nervous system are reflected by a broad spectrum of different clinical deficits. The reason for this is that inflammation may affect any part of the nervous system. Nevertheless, certain regions in the brain and spinal cord are more frequently affected than others. The topographical distribution of inflammatory lesions in the nervous system depends upon a large variety of different factors, which are different in the various infectious and autoimmune diseases. Aim of this short review is to discuss the main factors determining lesional topography in brain inflammation and to illustrate these patterns of tissue injury with clinical examples.

Host-Dependent Patterns of Tissue Injury in Invasive Pulmonary Aspergillosis

Host-Dependent Patterns of Tissue Injury in Invasive Pulmonary Aspergillosis

Host-Dependent Patterns of Tissue Injury in Invasive Pulmonary Aspergillosis

Invasive pulmonary aspergillosis (IPA) is an important cause of morbidity and mortality in neutropenic, nonneutropenic, and other immunocompromised patients. We therefore compared the patterns of infection and inflammation among 3 cohorts of immunocompromised patients with profound neutropenia, nonneutropenic immunosuppression, and hematopoietic stem cell transplantation. Lesions of IPA in neutropenic patients and hematopoietic stem cell transplant (HSCT) recipients were similar and consisted predominantly of angioinvasion and intraalveolar hemorrhage. The frequency of these histologic findings in neutropenic patients and HSCT recipients differed significantly from those of nonneutropenic patients (P < .05). It is noteworthy that even if HSCT recipients have normal peripheral blood neutrophil counts, there may be no influx into sites of infection. In the nonneutropenic cohort, lesions of IPA consisted mainly of neutrophilic and monocytic infiltrates and inflammatory necrosis. Thus, the status of innate host defenses contributes significantly to the histologic patterns observed in IPA.

Clinical course, pathological correlations, and outcome of biopsy proved inflammatory demyelinating disease

Background: A pathological classification has been developed of early active multiple sclerosis (MS) lesions that reveals four patterns of tissue injury: I—T cell/macrophage associated; II—antibody/complement associated; III—distal oligodendrogliopathy, and IV—oligodendrocyte...

CCR5Δ32 polymorphism effects on CCR5 expression, patterns of immunopathology and disease course in multiple sclerosis

Four distinct patterns of tissue injury have been described in multiple sclerosis (MS) lesions. Infiltrating monocytes in lesions of all patterns co-express CCR1 and CCR5. However, in pattern II lesions, the number of CCR1 cells is decreased, while the number of CCR5 expressing cells is increased in late active versus early active regions. In contrast, CCR1 and CCR5 cells were equal in all regions of pattern III lesions. These suggest distinct inflammatory microenvironments in pattern II and III lesions and support MS pathological heterogeneity. A deletion in CCR5 ( CCR5*Δ32), which encodes a truncated, non-functional protein, has been associated with late onset of MS and a favorable prognosis. We studied the association of CCR5*Δ32 with the course and severity of MS in 221 patients from a population-based cohort in Olmsted County, MN, and with patterns of immunopathology in 94 patients with biopsy-derived, pathologically confirmed demyelinating disease participating in the MS Lesion Project. The frequency of the genotypes in 221 patients from Olmsted County, MN, was 167 (75.6%) wild type, 52 (23.5%) heterozygotes, and 2 (0.9%) homozygotes. There was no association of carrier status for the CCR5*Δ32 mutation with disease severity as analyzed using the disease severity score (ranking of EDSS/duration stratified by duration), age of onset, gender or disease course (bout onset versus primary progressive). Due to low frequency of homozygotes no conclusion can be made regarding their relation to heterozygosity or wild-type status. The frequency of genotypes in the 94 biopsies was 77 (81.9%) wild type, 15 (16.0%) heterozygotes and 2 (2.1%) homozygotes. Carrier status for the CCR5*Δ32 mutation was not associated with patterns of immunopathology in MS. Despite similar numbers of T-lymphocytes, there were no CCR5+ T-cells nor was CCR5 expressed in the CNS of a homozygous CCR5*Δ32 MS patient, and heterozygous patients had reduced CCR5 expression compared to wild type patients. CCR5*Δ32 has a dose effect on CCR5 expression in the CNS, but is neither necessary for development of MS, nor CD3+ T cell recruitment into the CNS. Furthermore it does not segregate with patterns of immunopathology in MS. We did not find an association between CCR5*Δ32 mutation and disease severity and age of onset in MS.

Facial Soft Tissue Injuries as an Aid to Ordering a Combination Head and Facial Computed Tomography in Trauma Patients

While the trauma computed tomography (CT) head scan is frequently ordered during resuscitation of multiply injured patients, determining when also to order facial CT in these situations can be difficult. Consequently, facial fractures are commonly missed on initial imaging evaluation. In acute trauma situations, facial soft tissue injury markers are often used to aid in this decision. A study was undertaken to identify exactly which facial soft tissue injuries correlate with facial fractures and which did not. The aim of our research was to compare the facial soft tissue injury patterns of patients receiving a combination head and facial CT who had facial fractures versus those who had no facial fractures. A retrospective trauma registry review was performed for a 5-year period at Legacy Emanuel Hospital, a level 1 trauma center. The trauma team saw a total of 9,871 trauma patients and 49.9% required head CT as part of their initial evaluation. A total of 777 (15.7%) patients had a combination head and facial CT in which 477 (61.4%) had a facial fracture and 300 (38.6%) had no facial fracture. Statistical significance was established using Bonferroni corrected P values less than .05. Lacerations occurring in areas of the lips, nose, and intraorally, as well as wounds leading to periorbital contusion and subconjunctival hemorrhage, were significantly prevalent in the fracture group. Conversely, scalp lacerations and scalp contusions were significantly higher in the nonfracture group. Other injuries such as lacerations of the tongue, chin, forehead, cheek, ear, eyelid, and eyebrow were indistinguishable between both groups. Our data demonstrate that there are certain facial soft tissue injury zones that correlate with facial fractures in trauma patients who obtain head CT. We would like to propose that the acronym LIPS-N (Lip laceration, Intraoral laceration, Periorbital contusion, Subconjunctival hemorrhage, and Nasal laceration) be used in conjunction with a physical examination when assessing if a trauma patient who is getting head CT should also get facial CT.

Tissue preconditioning may explain concentric lesions in Baló's type of multiple sclerosis

Lesions of Baló's concentric sclerosis are characterized by alternating layers of myelinated and demyelinated tissue. The reason for concentric demyelination in this variant of multiple sclerosis is unclear. In the present study we investigated the immunopathology in autopsy tissue of 14 patients with acute multiple sclerosis or fulminant exacerbations of chronic multiple sclerosis with Baló-type lesions in the CNS, focusing on the patterns of tissue injury in actively demyelinating lesions. We found that all active concentric lesions followed a pattern of demyelination that bears resemblances to hypoxia-like tissue injury. This was associated with high expression of inducible nitric oxide synthase in macrophages and microglia. At the edge of active lesions and, less consistently, in the outermost layer of preserved myelin, proteins involved in tissue preconditioning, such as hypoxia-inducible factor 1alpha and heat-shock protein 70, were expressed mainly in oligodendrocytes and to a lesser degree also in astrocytes and macrophages. Due to their neuroprotective effects, the rim of periplaque tissue, where these proteins are expressed, may be resistant to further damage in an expanding lesion and may therefore remain as a layer of preserved myelinated tissue.

Mitochondrial damage and histotoxic hypoxia: a pathway of tissue injury in inflammatory brain disease?

The immunological mechanisms leading to tissue damage in inflammatory brain diseases are heterogeneous and complex. They may involve direct cytotoxicity of T lymphocytes, specific antibodies and activated effector cells, such as macrophages and microglia. Here we describe that in certain inflammatory brain lesions a pattern of tissue injury is present, which closely reflects that found in hypoxic conditions of the central nervous system. Certain inflammatory mediators, in particular reactive oxygen and nitrogen species, are able to mediate mitochondrial dysfunction, and we suggest that these inflammatory mediators, when excessively liberated, can result in a state of histotoxic hypoxia. This mechanism may play a major role in multiple sclerosis, not only explaining the lesions formed in a subtype of patients with acute and relapsing course, but also being involved in the formation of diffuse "neurodegenerative" lesions in chronic progressive forms of the disease.

Investigation of the thermal and tissue injury behaviour in microwave thermal therapy using a porcine kidney model

Minimally invasive microwave thermal therapies are being developed for the treatment of small renal cell carcinomas (RCC, d<3 cm). This study assessed the thermal history and corresponding tissue injury patterns resulting from microwave treatment of the porcine renal cortex. Three groups of kidneys were evaluated: (1) in vitro treated, (2) in vivo with 2-h post-treatment perfusion (acute) and (3) in vivo with 7-day post-treatment perfusion (chronic). The kidneys were treated with an interstitial water-cooled microwave probe (Urologix, Plymouth, MN) that created a lesion centered in the renal cortex (50 W for 10 min). The thermal histories were recorded at 0.5 cm radial intervals from the probe axis for correlation with the histologic cellular and vascular injury. The kidneys showed a reproducible 2 cm chronic lesion with distinct histologic injury zones identified. The thermal histories at the edge of these zones were found using Lagrangian interpolation. The threshold thermal histories for microvascular injury and stasis appeared to be lower than that for renal epithelial cell injury. The Arrhenius kinetic injury models were fit to the thermal histories and injury data to determine the kinetic parameters (i.e. activation energy and frequency factor) for the thermal injury processes. The resultant activation energies are consistent in magnitude with those for thermally induced protein denaturation. A 3-D finite element thermal model based on the Pennes bioheat equation was developed and solved using ANSYS (V7.0). The real geometry of the kidneys studied and temperature dependent thermal properties were used in this model. The specific absorption rate (SAR) of the microwave probe required for the thermal modelling was experimentally determined. The results from the thermal modelling suggest that the complicated change of local renal blood perfusion with temperature and time during microwave thermal therapy can be predicted, although a first order kinetic model may be insufficient to capture blood flow changes. The local blood perfusion was found to be a complicated function of temperature and time. A non-linear model based on the degree of vascular stasis was introduced to predict the blood perfusion. In conclusion, interstitial microwave thermal therapy in the normal porcine kidney results in predictable thermal and tissue injury behaviour. Future work in human kidney tissue will be necessary to confirm the clinical significance of these results.

Diffusion-weighted MRI in diffuse axonal injury of the brain.

The goal of this study was to identify and describe the different types and patterns of tissue injury which are encountered by diffusion-weighted imaging (DWI) in diffuse axonal injury (DAI) of the brain. The DWI data sets of 98 patients who suffered from a closed-head injury were retrospectively evaluated. Medical records were reviewed to rule out pre-existing neurological diseases. Lesions were studied for their DWI signal characteristics and lesion size or extension. Traumatic lesions were classified into three categories depending on their signal characteristica on DWI and apparent diffusion coefficient (ADC) maps: type 1, DWI- and ADC-hyperintense most likely representing lesions with vasogenic edema; type 2, DWI-hyperintense, ADC-hypointense indicating cytotoxic edema; type 3, central hemorrhagic lesion surrounded by an area of increased diffusion. According to the size and extent of lesions, injury was classified into three groups: group A, focal injury; group B, regional/confluent injury; and group C, extensive/diffuse injury. Our study showed that diffusion-weighted imaging differentiates between lesions with decreased and increased diffusion in patients with DAI. Different degrees of tissue injury extent were noticed. Future prospective studies should study if this additional information can be used as a predictor of injury reversibility, final outcome and prognosis.

The effect of aprotinin on ischemia–reperfusion injury in the rabbit kidney

Tissue subjected to a period of ischemia undergoes functional and morphological damage that increases during the reperfusion phase. In this study, the protective effect of aprotinin, which is a protease inhibitor, was assessed in a rabbit unilateral renal ischemia–reperfusion (I/R) model. New Zealand rabbits, weighing 1.5–2 kg, were randomized to receive either aprotinin 30.000 KIU kg−1and 10.000 KIU kg−1h−1i.v. infusion (group I, n= 7) or equivalent volumes of 0.09% sodium chloride (SF) (group II, control, n= 7) i.v. 15 minutes before a 45 minutes interruption of left renal artery blood flow and then 45 minutes of reperfusion. Blood samples were obtained before and after the ischemia–reperfusion period for measurement of nitric oxide serum (NO) levels with the nitrite/nitrate colorimetric method. Histological changes were evaluated by quantitative measurements using a numerical score (0–4) and immunohistochemical analysis of inducible nitric oxide synthase (iNOS) expression was determined. A Wilcoxon W -test was used for statistical analysis of biochemical measurements and mean values were expressed as ±sd. Histological examination revealed the distinctive pattern of ischemic renal tissue injury with obvious signs of epithelial necrosis. The intensity of epithelial necrosis was more extensive in the SF group. Immunohistochemical analysis showed that there was severe immunostaining in the tubular epithelium in both cortical and medullary regions and iNOS expression was more intense in SF-only cases. The staining results for aprotinin cases did not differ much from the non-ischemic kidney. Biochemical analysis revealed an increase in serum NO levels in both groups (P< 0.05), but this was more evident in the SF group (mean NO levels were 38.63 ± 19.03μ mol L−1in group I, 50.63 ± 24.28 μ mol L−1in group II). No statistically important difference was observed between the two groups. These resultssuggest that aprotinin may be beneficial in the prevention of systemic inflammation after transient renal ischemia.

Pathomorphology of laser-induced interstitial tumor thermotherapy of the liver

The aim of this study was to analyse pathomorphological findings after treatment with laser induced tumor thermotherapy (LITT) on liver tissue and to correlate the results with magnetic resonance imaging. LITT was performed ex vivo and in vivo using a Neodym-YAG-Laser. Lesions were monitored by MR-thermometry ex vivo and by contrast-enhanced MRI in vivo. After LITT the lesions were examined macroscopically, histologically, and electronmicroscopically. LITT-induced tissue damage was qualitatively evaluated, classified, and quantified by means of digital image analysis. Four different zones of tissue damage were identified within the lesions. Adjacent to the applicator the tissue was completely ablated while more peripheral lesions exhibited only sublethal cell damages seen by EM. In vivo the pattern of tissue injury followed the lobular architecture of the liver tissue. Ultrastructural examination revealed only in areas of minor tissue injury intact sinusoidal patterns. MRI overestimated the diameter of the core zone of complete tissue ablation both ex vivo and to a lesser extent in vivo.

Predictors of diabetic renal lesions in type 2 diabetes associated with microalbuminuria

Not all type 2 diabetic patients with microalbuminuria show the same pattern of renal tissue injury, and heterogeneity in renal lesions has been reported. We determine clinical and laboratory findings that predict the presence of typical diabetic glomerulosclerosis in type 2 diabetic patients with microalbuminuria. Twenty-three type 2 diabetic patients with microalbuminuria who underwent renal biopsy were investigated. Two patterns of renal biopsy findings were defined as type D (typical diabetic glomerulosclerosis) and type A (atherosclerotic nephropathy without evidence of diabetic glomerulopathy). Thirteen patients (57%) were classified as type D, and 10 (43%) as type A. In stepwise multiple regression analysis, severity of diabetic retinopathy (P = 0.0006), relatively high urinary N-acetyl-beta-D-glucosaminidase activity (P = 0.0013), and relatively low serum creatinine concentration (P = 0.0303) significantly predicted type D findings as opposed to type A (R2 = 0.734, P < 0.001). Certain patient characteristics can predict the presence of typical diabetic glomerulosclerosis in type 2 diabetic patients with microalbuminuria.

Soft tissue injuries to USA paralympians at the 1996 summer games

Nyland J, Snouse SL, Anderson M, Kelly T, Sterling JC. Soft tissue injuries to USA paralympians at the 1996 summer games. Arch Phys Med Rehabil 2000;81:368-73. Objective: To report the soft tissue injuries sustained by the members of four disabled sports organizations (DSOs) who competed as the USA Team at the 1996 Paralympic Games. Setting: 1996 Paralympic Games, Atlanta, Georgia. Methods: Soft tissue (strain, sprain, tendonitis, bursitis, or contusion) injury frequencies sustained by Disabled Sports USA (DSUSA, n = 66), the United States Association for Blind Athletes (USABA, n = 53), the United States Cerebral Palsy Athletic Association (USCPAA, n = 56), and Wheelchair Sports USA (WSUSA, n = 129) athletes were compared by body region with chi-square tests (p <.05) and standardized residual assessment. Results: A total of 254 soft tissue injuries (67% acute onset, 170/254) were sustained by the participant DSO members. Statistical design limitations and poor USCPAA athlete homogeneity prompted their exclusion from group comparisons (descriptive results are reported). The most common injury regions for specific DSOs were shoulder (26%), hip-thigh (14%), and ankle (12%) for DSUSA; hip-thigh (21%), cervicothoracic region (19%), and shoulder (17%) for USABA; lumbar region (14%), foot-toe (13%), and ankle (9%) for USCPAA; and shoulder (18%), arm-elbow (12%), forearm-wrist (12%), and lumbar region (9%) for USUSA. Chi-square residual analysis showed that the USABA athletes contributed more to cervicothoracic and lower leg region injury frequencies than DSUSA or WSUSA athletes. The WSUSA athletes contributed more to elbow-arm and forearm-wrist region injury frequencies than DSUSA or USABA athletes. The DSUSA athletes contributed more to ankle region injury frequencies than USABA or WSUSA athletes. Conclusions: Differences in soft tissue injury frequency among athletes of differing DSOs suggest that the competitive use of adaptive or assistive devices, in combination with sport-specific stressors and the athletes' disabilities, is related to the development of predictable soft tissue injury patterns. The decreased incidence of shoulder injury among WSUSA athletes suggests that the injury prevention advice provided by previous studies is being implemented among athletes at this competitive level. The increased incidence of ankle injuries among DSUSA athletes suggests lower extremity load imbalances (prosthetic vs uninvolved) during running. The increased incidence of lower leg injuries among USABA athletes suggests “overuse” injury patterns typical of nondisabled runners, or inadvertent contacts (contused shins), whereas the increased incidence of cervicothoracic injuries suggests injuries related to falls, “near falls,” or sudden directional changes prompted by guidance aids. © 2000 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation

Soft tissue injuries to USA Paralympians at the 1996 summer games

Objective: To report the soft tissue injuries sustained by the members of four disabled sports organizations (DSOs) who competed as the USA Team at the 1996 Paralympic Games.Setting: 1996 Paralympic Games, Atlanta, Georgia.Methods: Soft tissue (strain, sprain, tendonitis, bursitis, or contusion) injury frequencies sustained by Disabled Sports USA (DSUSA, n = 66), the United States Association for Blind Athletes (USABA, n = 53), the United States Cerebral Palsy Athletic Association (USCPAA, n = 56), and Wheelchair Sports USA (WSUSA, n = 129) athletes were compared by body region with chi-square tests (p<.05) and standardized residual assessment.Results: A total of 254 soft tissue injuries (67% acute onset, 170254) were sustained by the participant DSO members. Statistical design limitations and poor USCPAA athlete homogeneity prompted their exclusion from group comparisons (descriptive results are reported). The most common injury regions for specific DSOs were shoulder (26%), hip-thigh (14%), and ankle (12%) for DSUSA; hip-thigh (21%), cervico-thoracic region (19%), and shoulder (17%) for USABA; lumbar region (14%), foot-toe (13%), and ankle (9%) for USCPAA; and shoulder (18%), arm-elbow (12%), forearm-wrist (12%), and lumbar region (9%) for USUSA. Chi-square residual analysis showed that the USABA athletes contributed more to cervicothoracic and lower leg region injury frequencies than DSUSA or WSUSA athletes. The WSUSA atthletes contributed more to elbow-arm and forearm-wrist region injury frequencies than DSUSA or USABA athletes. The DSUSA athletes contributed more to ankle region injury frequencies than USABA or WSUSA athletes.Conclusions: Differences in soft tissue injury frequency among athletes of differing DSOs suggest that the competitive use of adaptive or assistive devices, in combination with sport-specific stressors and the athletes' disabilities, is related to the development of predictable soft tissue injury patterns. The decreased incidence of shoulder injury among WSUSA athletes suggests that the injury prevention advice provided by previous studies is being implemented among athletes at this competitive level. The increased incidence of ankle injuries among DSUSA athletes suggests lower extremity load imbalances (prosthetic vs uninvolved) during running. The increased incidence of lower leg injuries among USABA athletes suggests “overuse” injury patterns typical of nondisabled runners, or inadvertent contacts (contused shins), whereas the increased incidence of cervicothoracic injuries suggests injuries related to falls, “near falls,” or sudden directional changes prompted by guidance aids.

DIAGNOSTIC EVALUATION IN GASTROESOPHAGEAL REFLUX DISEASE

Gastroesophageal reflux disease (GERD) describes the clinical manifestations of reflux of gastric contents and the associated symptoms and patterns of tissue injury. Although its exact prevalence is difficult to determine, there is no doubt the GERD is the most common esophageal disease and probably among the most prevalent conditions seen in the primary care setting. GERD has a wide clinical spectrum, making the diagnostic evaluation challenging and complicated at times. Confirmatory test are rarely needed in patients with typical symptoms of heartburn or regurgitation who have a good clinical response to GERD therapy. This article describes the diagnostic tests necessary for some cases of GERD.

HuR, a novel target of anti-Hu antibodies, is expressed in non-neural tissues

Paraneoplastic encephalomyelitis (PEM) is characterized by a diverse set of clinical signs that are limited to the nervous system. The serologic hallmark of PEM is the presence of circulating autoantibodies, collectively referred to as `anti-Hu,' which immunoreact specifically with members of the Elav protein family. Until recently, the ELAV antigens were only detected in neurons, thus strongly supporting a role for anti-Hu antibodies in the selective neural tissue injury in PEM. The identification of HuR, however, a new member with a broad, non-neural pattern of RNA expression, raises several fundamental questions regarding PEM. First, why are non-neural tissues spared in PEM? Second, why is PEM predominantly associated with neuroendocrine tumors? To begin addressing these questions, we sought to determine whether the antibody response to HuR differs from the neural-specific counterparts in patients with PEM, and to characterize the protein expression pattern of this novel antigen in peripheral tissues and tumors. Using sera from 11 patients with Hu-positive PEM, we found that the majority of samples (73%) were weakly or non-reactive for recombinant HuR on Western blot, in contrast to consistently strong immunoreactivity with the neural-specific members HuD and Hel-N1. We also demonstrate that HuR is expressed at the protein level in both non-neural tissues and non-neuroendocrine tumors. These findings suggest that immunoreactive differences among Elav family members may contribute to the neural-restrictive pattern of tissue injury in patients with PEM.