STIM1 calcium sensor is required for activation of the phagocyte oxidase during inflammation and host defense.

The stromal-interacting molecule 1 (STIM1) is a potent sensor of intracellular calcium, which in turn regulates entry of external calcium through plasma membrane channels to affect immune cell activation. Although the contribution of STIM1 to calcium signaling in lymphocytes has been well studied, the role of this protein in neutrophil-mediated inflammation and host defense is unknown. We report that STIM1-deficient murine neutrophils show loss of store-operated calcium entry (SOCE) in response to both soluble ligands that activate G-proteins as well as Fcγ-receptor or integrin ligation that activates tyrosine kinase signaling. This results in modest defects in phagocytosis and degranulation responses but a profound block in superoxide production by the phagocyte oxidase. We trace the primary intracellular target of calcium to be protein kinase C isoforms α and ß (PKCα and PKCß), which in turn phosphorylate subunits of the oxidase leading to superoxide production. In vivo the loss of SOCE in stim1(-/-) chimeric mice results in marked susceptibility to bacterial infections but also protection from tissue injury in hepatic ischemia/reperfusion injury. These results demonstrate the critical role of STIM1-mediated SOCE and define major protein targets of calcium signaling in neutrophil activation during inflammatory disease.

Rasamsonia argillacea pulmonary and aortic graft infection in an immune-competent patient.

Rasamsonia argillacea (formerly known as Geosmithia argillacea) is a fungus recently recognized as a pathogen of immunocompromised patients. Here we report the first case of Rasamsonia infection in an immunocompetent host, presenting as a pulmonary and aortic graft infection. Its morphological similarity to nonpathogenic Penicillium species delayed the diagnosis and initiation of appropriate treatment.

Lack of NKX2.2 expression in bronchopulmonary typical carcinoid tumors: implications for patients with neuroendocrine tumor metastases and unknown primary site.

BACKGROUND: Patients with neuroendocrine tumors (NETs) may have metastatic disease and unknown primary site. NETs commonly arise from the bronchopulmonary (BP) and gastrointestinal (GI) tract. The largest subgroups of well-differentiated BP-NETs are typical carcinoids (TCs). The homeodomain transcription factor NKX2.2 regulates development of gut serotonin cells and is a marker of GI-NETs. Previous work on a limited number of samples suggested that BP-TCs do not express NKX2.2. We hypothesized that lack of NKX2.2 expression in BP-TCs might be useful to distinguish BP- from GI-NETs, and evaluated NKX2.2 expression in a larger number of BP-TCs. METHODS: Archived formalin-fixed, paraffin-embedded tissues were obtained from 13 previously undescribed patients with BP-TCs. Expression of NKX2.2, serotonin, and the NE marker chromogranin A (CgA) were assessed by immunohistochemistry. RESULTS: CgA expression was robust in all 13 BP-TCs, confirming the NE phenotype. Serotonin expression was less frequent (9/13; 69%). Two patients with BP-TCs in which serotonin expression was absent exhibited Cushing's syndrome due to ectopic ACTH production. NKX2.2 expression was not observed in any of the 13 tumors. CONCLUSIONS: Bronchopulmonary TCs uniformly express CgA but not NKX2.2. Because most of these tumors express serotonin, our findings suggest that NKX2.2 may not be required for serotonin production by BP-TCs. We conclude that the presence or absence of NKX2.2 expression may assist in the determination of the primary tumor site in patients with NET metastases of unknown origin. NET metastases that are CgA-positive/NKX2.2-negative would suggest a BP primary, whereas those that are CgA-positive/NKX2.2-positive would suggest a GI primary.

Benign thoracic disease in the elderly.

The spectrum of benign thoracic disease in the elderly includes structural abnormalities, infectious disease and their complications, benign neoplastic growths, and autoimmune disease. Differences in physiologic reserve in this population make diagnosis difficult, as elderly patients may not present in the classic fashion, as well as complicate treatment. Benign thoracic disease in the elderly can pose a challenging clinical problem. Older patients with comorbid diseases may have poor tolerance of unnecessary surgical interventions. However, benign disorders of the chest associated with symptoms attributable to effusion or obstruction of airways can limit quality of life. Minimally invasive techniques (eg, video-assisted thoracoscopic surgery) can limit the morbidity associated with intervention. Additionally, prompt intervention may spare the patient more invasive treatments. For example, early effusions can be managed with simple drainage rather than thoracotomy and decortication. With respect to suspected benign thoracic lesions in the elderly, guiding principles for management include avoiding unnecessary interventions while not overlooking potential malignancies. Close surveillance of progressive symptoms, ensuring no radiographic change in the size of the lesion over 2 years, and use of positron-emission tomography remain the diagnostic keys to accurate management.

Alterations in the proteome of pulmonary alveolar type II cells in the rat after hepatic ischemia-reperfusion.

OBJECTIVE: Hepatic ischemia-reperfusion can be associated with acute lung injury. Alveolar epithelial type II cells (ATII) play an important role in maintaining lung homeostasis in acute lung injury. DESIGN: To study potentially new mechanisms of hepatic ischemia-reperfusion-induced lung injury, we examined how liver ischemia-reperfusion altered the proteome of ATII. SETTING: Laboratory investigation. SUBJECTS: Spontaneously breathing male Zucker rats. INTERVENTIONS: Rats were anesthetized with isoflurane. The vascular supply to the left and medial lobe of the liver was clamped for 75 mins and then reperfused. Sham-operated rats were used as controls. After 8 hrs, rats were killed. MEASUREMENTS AND MAIN RESULTS: Bronchoalveolar lavage and differential cell counts were performed, and tumor necrosis factor-alpha and cytokine-induced neutrophil chemotactic factor-1 in plasma were determined by enzyme-linked immunosorbent assay. ATII were isolated, lysed, tryptically digested, and labeled using isobaric tags (iTRAQ). The samples were fractionated by cation exchange chromatography, separated by high-performance liquid-chromatography, and identified using electrospray tandem mass spectrometry. Spectra were interrogated and quantified using ProteinProspector. Quantitative proteomics provided quantitative data for 94 and 97 proteins in the two groups. Significant changes in ATII protein content included 30% to 40% increases in adenosine triphosphate synthases, adenosine triphosphate/adenosine diphosphate translocase, and catalase (all p < .001). Following liver ischemia-reperfusion, there was also a significant increase in the percentage of neutrophils in bronchoalveolar lavage (48% +/- 26%) compared with sham-operated controls (5% +/- 3%) (p < .01), and plasma tumor necrosis factor-alpha levels were also significantly increased. CONCLUSIONS: The proteins identified by quantitative proteomics indicated significant changes in moderators of cell metabolism and host defense in ATII. These findings provide new insights into possible mechanisms responsible for hepatic ischemia-reperfusion-related acute lung injury and suggest that ATII cells in the lung sense and respond to hepatic injury.

Esophageal erosion 9 years after anterior cervical plate implantation.

BACKGROUND: Anterior cervical discectomy and fusion is 1 of the most common spinal procedures performed. Most complications are observed during the intraoperative or immediate postoperative period. Long-term complications are not often described. A review of literature revealed 5 years as the longest complication interval. We present a case of esophageal erosion 9 years after initial surgery that was successfully treated. CASE DESCRIPTION: We describe a case of a 42-year-old woman who presented with recurrent pneumonia secondary to esophageal erosion almost 1 decade after anterior cervical spine surgery. This is the longest documented delay in presentation of esophageal erosion published to date. The diagnosis was made during EGD and the treatment consisted of plate removal and esophagus repair. The pertinent literature is reviewed and the therapeutic implications are discussed. CONCLUSIONS: In this report, we describe an uncommon case of esophageal erosion 9 years after anterior cervical plating. In cases of hardware migration even many years after surgery or in patients with intrinsic esophageal disease, potential esophageal damage should be considered.

Palliation of thoracic malignancies.

The sequelae of advanced malignancies of the chest, whether primary or metastatic, can be severely debilitating. In this review, we discuss the advances in palliative treatment for several intrathoracic complications of malignancy. The treatment of malignant pleural and pericardial effusions now includes a range of chemical sclerosants and percutaneous or surgical interventions. A new generation of promising stent and ablation technologies allows for the treatment of intrinsic or extrinsic airway obstruction. Similar techniques are being explored for esophageal obstruction, while the possible benefit of palliative radiation and chemotherapy continues to be investigated. Although their symptoms are often severe, patients with advanced thoracic malignancies have a growing number and variety of palliative treatment options to improve their quality of life.

Excision of Thoracic Chondrosarcoma: Case Report and Review of Literature.

Chondrosarcomas are cartilage-matrix-forming tumors that make up 20-27% of primary malignant bone tumors and are the third most common primary bone malignancy after multiple myelomas and osteosarcomas. Radiographic assessment of this condition includes plain radiography, computed tomography, and magnetic resonance imaging for tumor characterization and delineation of intraosseous and extraosseous involvement. Most chondrosarcomas are refractory to chemotherapy and radiation therapy; therefore, wide en bloc surgical excision offers the best chance for cure. Chondrosarcomas frequently affect the pelvis and upper and lower extremities. In rare instances, the chest wall can be involved, with chondrosarcomas occurring in the ribs, sternum, anterior costosternal junction, and posterior costotransverse junction. In this article, we present a patient with thoracic chondrosarcoma centered at the left T7 costotransverse joint with effacement of the left T7-T8 neuroforamen. We also detail our operative technique of wide en bloc chondrosarcoma excision and review current literature on this topic.

Stem cell activity of porcine c-kit+ hematopoietic cells.

OBJECTIVE: A marker for hematopoietic stem cells (HSCs) of pigs, which are considered to be the most suitable donors for clinical xenotransplantation, has not yet been identified. In this study, we examined the HSC activity of porcine c-kit+ bone marrow cells (BMCs). METHODS: The HSC activity of porcine c-kit+ BMCs was evaluated both in vitro using colony-forming unit (CFU) and cobblestone area-forming cell (CAFC) assays and in vivo in nonobese diabetic/severe combined immunodeficiency transgenic (NOD/SCID-Tg) mice carrying porcine cytokine transgenes. RESULTS: Purified c-kit+ BMCs were substantially enriched for both CFUs and CAFCs in vitro and their transplantation led to long-term porcine hematopoiesis in vivo in mice. Although porcine chimerism was detectable in the peripheral blood of NOD/SCID-Tg mice receiving porcine c-kit- BMCs at early time points after transplantation, the levels were markedly lower than those in mice receiving purified c-kit+ BMCs (0.2%+/-0.14% vs 7.7%+/-1.6% and 0.17%+/-0.17% vs 5.6%+/-2.1% at weeks 3 and 6, respectively). Importantly, all mouse recipients of porcine c-kit+ BMCs showed durable multilineage chimerism (>19 weeks), whereas no recipients of porcine c-kit- BMCs sustained long-term engraftment. Moreover, porcine HSCs that had engrafted for 19 weeks in the recipients of porcine c-kit+ BMCs gave rise to clonogenic progenitors in vitro and reconstituted porcine hematopoiesis in secondary recipients. CONCLUSION: The present study demonstrates that c-kit is an essential marker of both long-term-repopulating HSCs and progenitor cells with early engraftment capacity.

Use of CD9 expression to enrich for porcine hematopoietic progenitors.

OBJECTIVE: The aim of this study was to develop novel markers for enrichment of hematopoietic progenitors from bone marrow of swine. MATERIALS AND METHODS: We previously showed that pig bone marrow contains a "side population" (SP) of Hoechst dye-effluxing cells that resembles the hematopoietic stem cell (HSC)-containing murine SP and therefore represents a putative pig stem cell population. We screened a panel of monoclonal antibodies for those that allowed positive or negative enrichment of porcine SP cells and tested one of these for enrichment of hematopoietic progenitors in short-term and long-term in vitro assays. We then screened an expression library to clone the gene whose product is recognized by this antibody. RESULTS: Among a panel of 35 monoclonal lines screened, we found three that were useful for positive enrichment of SP cells and seven for negative enrichment. The 4-6 monoclonal line, allowing around 10-fold negative enrichment of SP cells, recognized the product of the porcine CD9 gene. Hematopoietic progenitors measured by short-term colony-forming unit and long-term cobblestone area-forming cell assays were around 10-fold enriched in the CD9(negative/low) fraction and were significantly depleted in the CD9(high) fraction. CONCLUSIONS: The antibody against the porcine CD9 gene product may be of use for enrichment of porcine hematopoietic stem cells. This approach to identify novel markers for enrichment of hematopoietic progenitors may be applicable to other mammalian species.

Anterior Transsternal Approach for Treatment of Upper Thoracic Vertebral Osteomyelitis: Case Report and Review of the Literature.

Direct ventral access to the cervicothoracic spine (C7-T4) poses a technical challenge in spine surgery, given the vital neurovascular structures residing anterior to the cervicothoracic junction (CTJ). The transsternal approach is a feasible surgical option that allows for direct anterior exposure of the lower cervical and upper thoracic vertebrae. Here, the authors report a case of an elderly gentleman with upper thoracic (T1-2) vertebral osteomyelitis and epidural abscess who underwent a transsternal full median sternotomy for ventral decompression and fusion of C7-T2. We also detail our operative procedure and review relevant literature on different transsternal approaches to the CTJ.

Circulatory support for fulminant myocarditis: consideration for implantation, weaning and explantation.

OBJECTIVE: Fulminant myocarditis (FM) is an uncommon but life-threatening condition for which a mechanical circulatory support (MCS) device can be life-saving. However, device selection, weaning and explantation procedures remain poorly defined. METHODS: Four patients were bridged to recovery using the Thoratec biventricular support device. All four were in a state of cardiogenic shock with rapid deterioration of their clinical status despite increasing doses of inotropes. Three patients required mechanical respiratory support, three were anuric and one was dialyzed. Echocardiography showed a mean ejection fraction of 12+/-8%. RESULTS: Each Thoratec implantation was performed on cardiopulmonary bypass with a beating heart. Three patients underwent biventricular cannulation. The fourth patient underwent left ventricular and right atrial cannulation. All patients manifested evidence of moderate to severe end organ dysfunction after device implantation. However, by explantation, end organ function had recovered in all patients. After a mean duration of 17+/-10 days, all the patients showed evidence of myocardial recovery. Recovery was confirmed on echocardiography which showed opening of the aortic valve and contraction of both ventricles. The weaning process was performed in 2-5 days by setting the device in a fixed mode and increasing the rate. Device explantation was uneventful in the four patients. At the 6 months echocardiography follow-up, all had normal systolic function. CONCLUSION: In patients with FM, biventricular support allows full circulatory support and unloads both ventricles until recovery occurs. In this set of patients, weaning and removal procedures are straight-forward. These results suggest an aggressive stance toward implantation of MCS in patients with FM.

Prognostic molecular assay might improve identification of patients at risk for recurrence in early-stage non-small-cell lung cancer.

INTRODUCTION: Adjuvant chemotherapy improves survival for some patients with NSCLC and is recommended in NCCN guidelines for stage Ib to IIa patients with certain "high-risk" characteristics. An internationally validated, 14-gene expression assay has been shown to better stratify mortality risk in nonsquamous NSCLC than either conventional staging or these high risk clinicopathologic features. PATIENTS AND METHODS: A blinded chart review of 52 patients with prospective molecular risk stratification using the 14-gene test compared recurrence outcomes with a mean follow-up of 15.2 ± 11.7 months of patients with high- or low-risk determined according to either NCCN criteria or the molecular assay. RESULTS: Molecular risk assessment was discordant from NCCN criteria in 14 of 23 patients in stages Ib and IIa (61%). Recurrence was not observed among any of 31 molecular intermediate- or low-risk patients, including 10 NCCN high-risk patients, whereas 2 of 6 recurrences (33%) occurred among NCCN low-risk patients. Recurrences in stages I or IIa were seen in 2 of 18 NCCN high-risk patients (11%; both were stage IIa and both received a high-risk molecular designation), and in 4 of 18 patients (22%) with a high-risk molecular score, including 1 stage Ia and 1 stage Ib patient. CONCLUSION: This small cohort study suggests that a 14-gene prognostic assay more accurately stratifies risk among early-stage NSCLC patients than current NCCN criteria. NCCN guidelines already advocate risk stratification within tumor, node, metastases stages. This molecular assay has clinical utility in better identifying high-risk patients and might improve NCCN adjuvant chemotherapy recommendations.

Anterior thoracolumbar corpectomies: approach morbidity with and without an access surgeon.

BACKGROUND: Anterior approaches for thoracolumbar corpectomies can have significant morbidity. Spine surgeons have historically performed their own anterior approaches, but recently access surgeons are being used more frequently. OBJECTIVE: To evaluate the morbidity rates of approaches performed by an access surgeon and by an approach-trained spinal neurosurgeon. METHODS: From 2004 to 2008, 46 patients undergoing anterior thoracolumbar corpectomies (levels T2-L5) by the senior author (D.C.) were identified and subdivided into 2 groups based on whether an access surgeon was involved. Nine patients were excluded, leaving 37 patients in the final analysis. Blood loss, operative times, length of hospital stay, complications, and neurological outcomes were evaluated. RESULTS: Eighteen patients had anterior spinal access by an approach-trained spinal neurosurgeon, and 19 patients underwent the approach by an access surgeon. Surgeries performed by the spinal neurosurgeon alone were comparable to those performed by an access surgeon with respect to operative time, days spent in the hospital, blood loss, complication rates, and improvement in neurological function. CONCLUSION: There appears to be no increased morbidity of anterior approaches performed by an approach-trained spinal neurosurgeon compared with approaches performed by an access surgeon in terms of operative time, complication rate, and improvement in neurological function.

A safe and reproducible anastomotic technique for minimally invasive Ivor Lewis oesophagectomy: the circular-stapled anastomosis with the trans-oral anvil.

OBJECTIVES: In expert hands, the intrathoracic oesophago-gastric anastamosis usually provides a low rate of strictures and leaks. However, anastomoses can be technically challenging and time consuming when minimally invasive techniques are used. We present our preliminary results of a standardised 25 mm/4.8mm circular-stapled anastomosis using a trans-orally placed anvil. MATERIALS AND METHODS: We evaluated a prospective cohort of 37 consecutive patients offered minimally invasive Ivor Lewis oesophagectomy at a tertiary referral centre. The oesophago-gastric anastomosis was created using a 25-mm anvil (Orvil, Autosuture, Norwalk, CT, USA) passed trans-orally, in a tilted position, and connected to a 90-cm long polyvinyl chloride delivery tube through an opening in the oesophageal stump. The anastomosis was completed by joining the anvil to a circular stapler (end-to-end anastomosis stapler (EEA XL) 25 mm with 4.8-mm staples, Autosuture, Norwalk, CT, USA) inserted into the gastric conduit. Primary outcomes were leak and stricture rates. RESULTS: Thirty-seven patients (mean age 65 years) with distal oesophageal adenocarcinoma (n=29), squamous cell cancer (n=5) or high-grade dysplasia in Barrett's oesophagus (n=3) underwent an Ivor Lewis oesophagectomy between October 2007 and August 2009. The abdominal portion was operated laparoscopically in 30 patients (81.1%). The thoracic portion was done using a muscle-sparing mini-thoracotomy in 23 patients (62.2%) and thoracoscopic techniques in 14 patients (37.8%). There were no intra-operative technical failures of the anastomosis or deaths. Five patients had strictures (13.5%) and all were successfully treated with endoscopic dilations. One patient had an anastomotic leak (2.7%) that was successfully treated by re-operation and endoscopic stenting of the anastomosis. DISCUSSION: The circular-stapled anastomosis with the trans-oral anvil allows for an efficient, safe and reproducible anastomosis. This straightforward technique is particularly suited to the completely minimally invasive Ivor Lewis oesophagectomy.

Emergent management of malignancy-related acute airway obstruction.

Acute obstruction of the airway in the emergent situation results from a wide variety of malignant and benign disease processes. Acute management involves establishing a secure and patent route for adequate gas exchange. This requires rapid determination of the location of the obstruction and nature of the obstruction followed by a thoughtful management approach based on findings. Difficult anatomy, hemorrhage, dense secretions, inflammation, and bulky tumor mass can significantly complicate the task of clearing the airway. Obstruction of the central airways by malignant tumor is associated with poor prognosis, but quality of life is considerably improved by restoration of adequate central airways. For both the patient and the clinician, the presentation can be frightening, and advanced interventional pulmonary/endobronchial techniques are required to achieve prompt relief of symptoms. The alleviation of central airway obstruction by tumor is most often palliative, with improvement of quality of life the primary goal rather than cure. This review will cover covers an approach to the patient with airway obstruction that results from malignancy involving the trachea or proximal bronchial tree and affecting gas exchange.

Gastroesophageal reflux in patients with idiopathic pulmonary fibrosis referred for lung transplantation.

OBJECTIVES: The association between gastroesophageal reflux disease and idiopathic pulmonary fibrosis has not been fully characterized. The aims of this study were to determine in patients with idiopathic pulmonary fibrosis (1) the prevalence of reflux symptoms, (2) the esophageal manometric profile, and (3) the prevalence of proximal and distal esophageal reflux. METHODS: Between May 1999 and March 2006, 30 patients with idiopathic pulmonary fibrosis were referred to the Swallowing Center at the University of California San Francisco. Each patient underwent a structured symptom assessment, esophageal manometry, and 24-hour dual sensor ambulatory pH monitoring. RESULTS: Twenty (67%) patients had abnormal esophageal reflux. Typical reflux symptoms, although more common in those with reflux, were not reliable as a screening test (sensitivity 65%, specificity 71%). Sixty-five percent of patients with abnormal reflux had a hypotensive lower esophageal sphincter. Abnormal esophageal peristalsis was more common among those with reflux (50% vs 10%; P = .03). In 9 (30%) patients, acid refluxed into the proximal esophagus for over 1% of the study time. CONCLUSIONS: A majority of patients with idiopathic pulmonary fibrosis have pathologic reflux. Symptoms do not distinguish between those with and without reflux. In these patients, reflux is associated with a hypotensive lower esophageal sphincter and abnormal esophageal peristalsis, and often extends into the proximal esophagus.

Oklahoma prosthesis: resection of tumor of clavicle and chest wall reconstructed with a custom composite graft.

Tumors involving the clavicle by primary or metastatic growth may require clavicular resection often with rib resection. The resulting cosmetic and functional impairment of clavicular resection may be significant with a sloped appearing shoulder girdle and chronically impaired movement of the upper extremity. We report a 48-year-old woman presenting with a bulky metastatic renal cell mass of her left clavicle extending to the chest wall. We report en-bloc clavilculectomy and chest wall resection with a novel method of reconstruction using a single methyl methacrylate and prolene composite prosthesis in a configuration resembling the state of Oklahoma.

Porcine mononuclear cells adhere to human fibronectin independently of very late antigen-5: implications for donor-specific tolerance induction in xenotransplantation.

To combat the shortage of donor organs, transplantation across species barriers has been proposed. Induction of tolerance would overcome the substantial immunologic barriers to xenotransplantation and would avoid the chronic use of immunosuppressive agents. Successful transplantation of hematopoietic cells induces robust specific tolerance to donor antigens in allogeneic and xenogeneic models. The beta1 integrin class of adhesion molecules and their interactions with extracellular matrix components are thought to be integral to the engraftment and maturation of hematopoietic stem cells. We therefore examined the efficacy of porcine very late antigen-5 (VLA-5) and VLA-4 interactions with the human extracellular matrix (ECM) protein, fibronectin. Peripheral blood mononuclear cells (PBMCs) from humans and miniature swine were flourochrome labeled and adhesion to plates coated with whole human fibronectin (whFN) or its 120 KDa fragment containing the VLA-5 binding region was determined. Flow cytometry and immuno- precipitation were used to identify a monoclonal antibody that cross-reacted on porcine VLA-5. Human and pig PBMC adhesion to human fibronectin (hFN) or 120 kDa fragment-coated plates was assessed following incubation with control ab, anti-VLA-4, anti-VLA-5, or soluble fibronectin. Using rabbit complement, cells expressing VLA-5 were purged from PBMC preparations before performing the adhesion assay. Porcine and human PBMC both adhered to hFN in a divalent cation-dependent and activation-dependent manner. Adhesion to hFN of human but not pig PBMC was blocked by anti-VLA-5 monoclonal antibody SAM-1, although this mAb immunoprecipitated a heterodimeric cell surface molecule (155/135 kDa) resembling VLA-5 from pig PBMC. Complement-mediated depletion of VLA-5-expressing cells ablated specific binding of human but not porcine cells to hFN and its 120 kDa fragment. Addition of soluble fibronectin was capable of blocking adhesion of PBMC of both species to hFN. Anti-VLA-4 reduced the binding of PBMC from both species to hFN to a similar extent. Human and pig cells can specifically adhere to hFN and its 120 kDa fragment, suggesting that this critical cell-ECM interaction is preserved across species. While human cells exclusively use VLA-5 for binding to the 120 kDa fragment, porcine cells could not be shown to adhere to whFN or its 120 kDa fragment via VLA-5. However, porcine VLA-4 is capable of mediating adhesion to human FN. We conclude that disparities in the adhesive interactions of beta1 integrins may be a barrier to the use of porcine hematopoietic stem cell transplantation as a means of inducing donor-specific tolerance in the pig to human species combination.