Distinctive space weathering on Vesta from regolith mixing processes.

The surface of the asteroid Vesta has prominent near-infrared absorption bands characteristic of a range of pyroxenes, confirming a direct link to the basaltic howardite-eucrite-diogenite class of meteorites. Processes active in the space environment produce 'space weathering' products that substantially weaken or mask such diagnostic absorption on airless bodies observed elsewhere, and it has long been a mystery why Vesta's absorption bands are so strong. Analyses of soil samples from both the Moon and the asteroid Itokawa determined that nanophase metallic particles (commonly nanophase iron) accumulate on the rims of regolith grains with time, accounting for an observed optical degradation. These nanophase particles, believed to be related to solar wind and micrometeoroid bombardment processes, leave unique spectroscopic signatures that can be measured remotely but require sufficient spatial resolution to discern the geologic context and history of the surface, which has not been achieved for Vesta until now. Here we report that Vesta shows its own form of space weathering, which is quite different from that of other airless bodies visited. No evidence is detected on Vesta for accumulation of lunar-like nanophase iron on regolith particles, even though distinct material exposed at several fresh craters becomes gradually masked and fades into the background as the craters age. Instead, spectroscopic data reveal that on Vesta a locally homogenized upper regolith is generated with time through small-scale mixing of diverse surface components.

The landing of the NEAR-Shoemaker spacecraft on asteroid 433 Eros.

The NEAR-Shoemaker spacecraft was designed to provide a comprehensive characterization of the S-type asteroid 433 Eros (refs 1,2,3), an irregularly shaped body with approximate dimensions of 34 x 13 x 13 km. Following the completion of its year-long investigation, the mission was terminated with a controlled descent to its surface, in order to provide extremely high resolution images. Here we report the results of the descent on 12 February 2001, during which 70 images were obtained. The landing area is marked by a paucity of small craters and an abundance of 'ejecta blocks'. The properties and distribution of ejecta blocks are discussed in a companion paper. The last sequence of images reveals a transition from the blocky surface to a smooth area, which we interpret as a 'pond'. Properties of the 'ponds' are discussed in a second companion paper. The closest image, from an altitude of 129 m, shows the interior of a 100-m-diameter crater at 1-cm resolution.

Imaging of small-scale features on 433 Eros from NEAR: evidence for a complex regolith.

On 25 October 2000, the Near Earth Asteroid Rendevous (NEAR)-Shoemaker spacecraft executed a low-altitude flyover of asteroid 433 Eros, making it possible to image the surface at a resolution of about 1 meter per pixel. The images reveal an evolved surface distinguished by an abundance of ejecta blocks, a dearth of small craters, and smooth material infilling some topographic lows. The subdued appearance of craters of different diameters and the variety of blocks and different degrees of their burial suggest that ejecta from several impact events blanketed the region imaged at closest approach and led to the building up of a substantial and complex regolith consisting of fine materials and abundant meter-sized blocks.

The frequency and clinical significance of neuroendocrine cells within stage III adenocarcinomas of the colon.

BACKGROUND: Although colon carcinomas consisting predominantly of neuroendocrine cells carry a worse prognosis than "routine" colon adenocarcinomas, the clinical significance of scattered neoplastic neuroendocrine cells within a typical colon adenocarcinoma remains controversial. The aim of this study was to document the frequency and clinical significance of neuroendocrine cell expression within a stage-specific group of typical adenocarcinomas of the colon. METHODS: Forty-eight patients with resected stage III adenocarcinomas of the colon were selected from our institutional tumor registry. The pathologic specimens from these patients were reviewed and underwent immunohistochemical staining for chromogranin, a sensitive and specific marker of neuroendocrine differentiation. Long-term (> or = 5 years) clinical outcome was compared with the presence of neuroendocrine cell expression. RESULTS: Twenty tumors (41.7%) stained positively for chromogranin. Twenty-two patients (45.8%) had long-term cancer-free survival, although chromogranin positivity did not correlate with this survival. CONCLUSION: The frequency of scattered neuroendocrine cells within colonic adenocarcinomas is high. This finding does not, however, carry the same adverse prognostic implications for cancer survival as does the presence of true neuroendocrine carcinoma of the colon.

Pulmonary clear cell carcinoid tumor: another entity in the differential diagnosis of pulmonary clear cell neoplasia.

A clear cell variant of primary pulmonary carcinoid tumor is described. The tumor arose in a 53-year-old woman who was incidentally found to have a solitary pulmonary nodule in the left upper lobe during routine chest roentgenography. Histologically, the tumor was composed of predominantly clear to lightly eosinophilic, polygonal cells with bland nuclei arranged in sheets and nests. Nuclear pleomorphism, necrosis, vascular invasion, and mitotic figures were not seen. The tumor cells were negative for oil-red-O and periodic acid-Schiff stains with and without diastase pretreatment on frozen and formalin-fixed sections, respectively. During immunohistochemical evaluation, the tumor cells were focally positive for cytokeratin and diffusely positive for neuron-specific enolase and chromogranin. Electron microscopy performed on paraffin block-retrieved tissue showed the presence of electron-dense, neurosecretory-type granules and variably sized vacuolated areas within the cytoplasm. the nature of which remained unclear. Intracytoplasmic glycogen or lipid were not identified. To our knowledge, this is the first report of pulmonary clear cell carcinoid tumor.

Improved clinical outcomes with liver transplantation for hepatitis B-induced chronic liver failure using passive immunization.

OBJECTIVE: The goals were to summarize the results of liver transplantation for chronic hepatitis B disease (HBV) at the University of Virginia, correlate pretransplant viral markers with posttransplant hepatitis B immunoglobulin (HBIg) requirements, and identify the relation between viral protein in the liver and clinical reinfection. SUMMARY BACKGROUND DATA: Liver transplantation is an accepted treatment for end-stage liver disease from chronic HBV infection, although lifelong antiviral treatment (with HBIg or antiviral agents) is still necessary. Patients with evidence of active viral replication (detectable serum HBV-DNA or e antigen) at the time of transplant have a higher rate of allograft infection. Whether clinically stable patients receiving HBIg immunoprophylaxis have detectable viral products in their grafts remains unknown. METHODS: Forty-four transplants performed for HBV disease at the University of Virginia since March 1990 were reviewed. Most patients underwent aggressive passive immunoprophylaxis with HBIg to maintain serum HBV surface antibody (HBsAb) levels > or =500 IU/l for the first 6 months after the transplant, and > or =150 IU/l thereafter. Patients had viral markers quantified, underwent pharmacokinetic analysis of HBsAb levels to adjust dosing, and were biopsied routinely every 3 to 6 months and when indicated. RESULTS: Forty-four transplants were performed in 39 patients. Actual 1-year and 3-year graft survival was 95% and 81%, respectively, and 1-year and 3-year patient survival was 98% and 96%, respectively. After the adoption of indefinite HBIg prophylaxis, nine grafts became infected (all in recipients positive for HBV e antigen). Three occurred within 8 weeks of transplantation and were associated with a short HBsAb half-life and a wild-type virus. Six occurred >8 months after the transplant, and most of these were associated with viral mutation. Quantification of pretransplant markers was an overall poor predictor of HBIg requirements after the transplant. Immunohistochemistry demonstrated transient low-level expression of core protein in the liver in 23% of patients without serum or clinical evidence of recurrent hepatitis. CONCLUSIONS: An excellent outcome is possible after liver transplantation for chronic HBV disease using HBIg dosed by pharmacokinetic parameters. Currently, quantification of pretransplant serum markers of the HBV antigen load does not predict the intensity of posttransplant treatment required for good clinical outcomes. Because HBV is not eradicated from the patient, some form of indefinite antiviral therapy continues to be warranted.

Clear cell tumors of the alimentary tract and abdominal cavity.

Clear cell neoplasms of the abdominal organs are represented by a variety of epithelial and mesenchymal neoplasms, of varying malignant potential. Several varieties of clear cell carcinomas, including those with tubulopapillary, hepatoid, colloid, or neuroendocrine features, have been described, as well as several benign epithelial neoplasms. These epithelial tumors have been reported in the gastrointestinal hollow viscera, as well as the liver, pancreas, and biliary tract. A second major consideration is the mesenchymal-derived gastrointestinal stromal tumors, which also may feature clear cells, and comprise a spectrum of biological behavior. Miscellaneous lesions include clear cell variants of melanoma and mesothelioma. This review includes histological details of the various entities, as well as important histochemical, immunohistological, and ultrastructural features. Pertinent differential diagnostic points are stressed, including distinction of the primary clear lesions from relevant metastatic neoplasms.

Gonadoblastomas in 45,X/46,XY mosaicism: analysis of Y chromosome distribution by fluorescence in situ hybridization.

Gonadoblastomas are composed of nests of neoplastic germ cells and sex cord derivatives surrounded by ovarian-type stroma. These tumors are found almost exclusively in persons with gonadal dysgenesis associated with a Y chromosome or Y chromosome fragment, and accordingly, the Y chromosome has been implicated in gonadoblastoma oncogenesis. To evaluate this association, we used two-color fluorescence in situ hybridization with chromosome-specific probes to determine the distribution of the X and Y chromosomes in the tumor nests and surrounding stromal cells in paraffin tissue sections of three gonadoblastomas in two patients with gonadal dysgenesis and 45,X/46,XY mosaicism. Statistical analysis of the data from the fluorescence in situ hybridization demonstrated that in all three gonadoblastomas, the proportion of nuclei with a Y chromosome signal was significantly higher in the tumor cells than in the nontumoral cells of the surrounding stroma (P<.001). These results suggest that Y chromosome material participates in gonadoblastoma tumorigenesis.

Hepatocytic globules in end-stage hepatic disease: relationship to alpha1-antitrypsin phenotype.

Hepatic explant specimens from 171 patients with cirrhosis were examined to determine the incidence of periodic acid-Schiff (PAS)-positive diastase-resistant globules (PDRGs) in end-stage hepatic disease and whether the globules bear a specific relationship to the alpha1-antitrypsin (A1AT) phenotype or to causes of hepatic disease other than A1AT deficiency. PAS-positive diastase-resistant globules were detected in 17 (10%) of the hepatic explant specimens, and the globules in all of these cases were strongly immunoreactive for A1AT. In the 17 patients with PDRGs, the cirrhosis was attributed preoperatively to A1AT deficiency (3 patients), ethanol abuse, viral hepatitis, or both (10 patients), cryptogenic cirrhosis (3 patients), and autoimmune hepatitis (1 patient). The A1AT isoelectric phenotypes classified according to the protease inhibitor (Pi) nomenclature for 16 of these patients were as follows: Pi ZZ (3 patients), Pi SS (1 patient), Pi MZ (8 patients), and Pi MM (4 patients). Because PDRGs were seen in a variety of A1AT phenotypes, serum electrophoretic analysis, not histologic examination, is required for the correct diagnosis of an A1AT abnormality. Furthermore, although PDRGs were seen in a variety of hepatic diseases, the majority of patients with globules had an undetected A1AT abnormality. Accordingly, on identification of hepatocytic PDRGs, the clinician should be alerted to the possibility of an unsuspected A1AT abnormality even in the presence of other causes of hepatic disease.

The early solar system.

Life arose on an early Earth which was the product to the conditions present, and processes operating, during formation of the solar system. The formation and early state of the solar system are reviewed in order to better understand the nature of the early Earth, and to constrain the conditions present during the origin and early evolution of life on this planet.

Papillary endolymphatic sac tumors: CT, MR imaging, and angiographic findings in 20 patients.

PURPOSE: To determine the computed tomographic (CT), magnetic resonance (MR) imaging, and angiographic findings of papillary endolymphatic sac tumors. MATERIALS AND METHODS: Clinical and imaging studies in 20 patients (aged 17-65 years) with histopathologically proved papillary endolymphatic sac tumors were retrospectively reviewed. Patients underwent CT (n = 18), MR imaging (n = 15), or angiography (n = 12). CT scans were evaluated for bone erosion and calcification; MR images, for signal intensity, enhancement patterns, and flow voids; and angiograms, for tumoral blood supply. RESULTS: All tumors were destructive and contained calcifications centered in the retrolabyrinthine region at CT. The MR imaging appearance varied with lesion size; 12 of 15 tumors showed increased signal intensity at T1-weighted imaging. The high-signal-intensity area was circumferential in lesions 3 cm or smaller and was scattered throughout the lesion in advanced tumors. Only tumors larger than 2 cm had flow voids. The blood supply arose predominantly from the external carotid artery. Large tumors had additional supply from the internal carotid and posterior circulation. CONCLUSION: Papillary endolymphatic sac tumors are destructive, hypervascular lesions that arise from the temporal bone retrolabyrinthine region. Increased signal intensity at unenhanced T1-weighted MR imaging is common and may help distinguish these lesions from more common, aggressive temporal bone tumors.

The international autoimmune hepatitis score in chronic hepatitis C.

Clinical and laboratory findings of autoimmunity are common in chronic hepatitis C. Autoimmune hepatitis (AIH), a disease of unknown cause, has been defined by use of the International Autoimmune Hepatitis Group Score (AIH score), which quantifies clinical and laboratory parameters. To further validate the specificity of the International AIH score and investigate the similarities between hepatitis C and AIH, we measured the International Autoimmune Hepatitis Group Score in patients with well-defined chronic hepatitis C. Thirty consecutive non-cirrhotic patients with chronic hepatitis C were evaluated. Scoring was performed using both components of the AIH score: a set of minimum required parameters including laboratory and historical data and a second set of additional parameters dominated by histological criteria. Autoantibodies were positive in 21 of 30 hepatitis C patients and associated (patient or first-degree relative) autoimmune diseases were present in eight of 30 patients. Histologically, chronic active hepatitis with periportal piecemeal necrosis was seen in 24 of 30 patients and lymphoid follicles in 16 of 30 patients. No patient scored as probable or definite AIH using the minimum required parameters of the AIH score. When histological parameters were included, four of 30 patients scored as probable AIH but none as definite AIH. Therefore, AIH was excluded by the minimal and additional criteria of the AIH score in 86% of patients with hepatitis C despite a high prevalence of autoantibodies in these patients. We conclude that the criteria set forth by the International AIH scoring system defines a distinct disease although it shares some features with chronic hepatitis C. Modification of the AIH scoring system to include other commonly accepted risk factors for hepatitis C and additional histological parameters would further improve its specificity.

Histopathologic changes associated with fialuridine hepatotoxicity.

Chronic hepatitis B is a widespread viral illness with the serious sequelae of cirrhosis and hepatocellular carcinoma. Current therapy with interferon is not universally efficacious, and this has led to the evaluation of other antiviral agents. A recent Phase II trial of the nucleoside analogue, fluoroiodoarabinofuranosyluracil (fialuridine, FIAU) was halted because of the sudden development of severe multisystem toxicity characterized by hepatic failure, lactic acidosis, and pancreatitis, which resulted in the deaths of five patients. We systematically evaluated pre- and post-therapy biopsy, explant, and autopsy specimens from the 15 patients involved in this trial to define the hepatic changes of fialuridine toxicity and to determine whether the degree of pre-existing hepatitis contributed to the severity of toxicity. Severe hepatotoxicity from fialuridine was characterized by hepatomegaly with diffuse, predominantly microvesicular steatosis, hepatocellular glycogen depletion, marked bile ductular proliferation, and cholestasis. Ultrastructural examination revealed intracytoplasmic lipid droplets and marked mitochondrial injury. Patients in whom severe toxicity did not develop mainly showed changes caused by the underlying chronic hepatitis B alone. There was a subtle increase in the amount of microvesicular steatosis in two of six patients with mild or no symptoms of toxicity. The microscopic and ultrastructural pattern of injury and systemic symptoms in patients with fialuridine toxicity are consistent with severe mitochondrial and metabolic derangements. Similar hepatic pathologic findings have been reported rarely for other antiviral nucleoside analogues, which suggests that the mechanisms of toxicity might be related.

Predictive value of intraoperative biopsies and liver function tests for preservation injury in orthotopic liver transplantation.

Eighty liver allografts were studied to determine the predictive value of intraoperative biopsies and postoperative liver function tests for the development of preservation injury (PI). Peak transaminase (aspartate transaminase [AST] and alanine transaminase [ALT]) and prothrombin time (PT) values achieved by each patient during postoperative days (POD) 1 through 7 were determined. PI in day 0 preperfusion biopsies (0Pre) (obtained immediately before implantation) and postperfusion biopsies (0Post) (obtained immediately after revascularization) was categorized by histological criteria as present or absent. PI in biopsies taken during POD 2 through 14 was histologically graded as either moderate-to-severe, mild, or absent. Of the 80 allografts, 8 were omitted because of primary nonfunction or postoperative complications. 0Pre and 0Post biopsies were available on 25 of 72 (35%) and 69 of 72 (96%) allografts, respectively. Only 2 (8%) of the 0Pre biopsies showed histological PI compared with 48 (70%) of the 0Post biopsies. Fifty-nine patients were biopsied between POD 2 through 14. Of these, 15, 28, and 16 patients developed moderate-to-severe, mild, or no evidence of PI, respectively. The presence of PI in the 0Post biopsy strongly correlated with the development of PI during POD 2 through 14 (P < .0005). Peak AST and ALT values in patients with moderate-to-severe PI on POD 2 through 14 were significantly elevated compared with those patients with either mild (P = .01 and .03) or no PI (P = .02 and .006). Because of extensive overlap in AST and ALT values between the three groups, however, transaminase values were not useful in predicting the presence or absence of PI in the individual case. The development of PI during POD 2 through 14 correlated with advanced donor age (P = .06) but was unassociated with 0Pre biopsy findings, cold ischemia time, or peak PT values. We conclude that the 0Post biopsy is a valuable tool for the prediction of subsequent PI in the early postoperative period. In contrast, 0Pre biopsy findings and peak AST and ALT values are not useful in the assessment of PI.

Clear cell tumors of the lower respiratory tract.

Clear cell tumors of the lower respiratory tract comprise a diverse group of lesions. The prototypical lesion is the benign clear cell tumor or "sugar tumor," a tumor of enigmatic histogenesis, whose name derives from the high glycogen content of the cells. Analogous to the salivary gland lesion of the same name, acinic cell tumors may also occur in the tracheobroncheal tree. The topic of "clear cell carcinoma" is discussed, which in the opinion of the authors does not constitute a distinct tumor entity. A discussion of potential lesion metastatic to the lung with clear cell histology is also presented. Histological details of the various entities are discussed, as well as the significant histochemical, immunohistological, and electron microscopic features; in particular, such findings that are relevant to differential diagnosis are stressed, including the distinction of primary and metastatic lesions.

Accuracy and significance of pretransplant liver volume measured by magnetic resonance imaging.

Measurement of liver volume in patients with advanced liver disease is used to gauge the appropriate size of donor organs and may have prognostic value. We sought to determine the accuracy of magnetic resonance imaging (MRI) in measuring liver volume in 19 adult patients under consideration for liver transplantation. We also correlated the liver volume determination to the clinical severity of disease. Liver volume was measured at MRI by averaging the calculated volumes from coronal and transverse breath-hold T1-weighted images. These results were compared to the explanted liver volume measured by fluid displacement and the explant mass. The correlation coefficient for MRI liver volume and the explant displacement volume was 0.90. The mean liver volume for Child-Pugh class AB by MRI was 1986 +/- 568 mL (1002-2470 mL) compared to 1433 +/- 379 mL (540-1889 mL) in Child-Pugh class C patients (p = .02). We conclude that MRI offers an anatomically accurate means of determining adult liver volume in vivo. Lower mean liver volumes were observed in Child-Pugh class C patients. In addition to its ability to provide tumor screening and vascular assessment, MRI is able to provide accurate determinations of liver volume in patients undergoing liver transplant evaluations.

Human papillomavirus and Epstein-Barr virus in sinonasal Schneiderian papillomas. An in situ hybridization and polymerase chain reaction study.

Using the polymerase chain reaction (PCR), it has been recently reported that the Epstein-Barr virus (EBV) is present in the majority of Schneiderian sinonasal papillomas (SNP) of the inverted type and may play a role in the pathogenesis of these lesions. The reported prevalence rates of human papillomavirus (HPV) in different types of SNP is also controversial and in need of clarification. Twenty-eight SNP from 27 patients were histologically classified and evaluated for evidence of EBV using PCR and 2 different sensitive and specific in situ hybridization (ISH) procedures for EBER1. Similarly, two methods of ISH were also used for the detection of HPV, using biotinylated DNA probes sensitive for 14 different HPV types as well as more sensitive and specific radioactive RNA probes for HPV types 6, 11, and 16. Polymerase chain reaction was successful in 19 papillomas, including 12 of 19 inverted SNP, 1 of 1 inverted SNP with squamous cell carcinoma, 4 of 5 fungiform SNP, and 2 of 3 oncocytic lesions. Southern blot hybridization of PCR products showed the presence of EBV DNA in two lesions, including one inverted SNP and the single inverted SNP with squamous cell carcinoma. By both DNA- and RNA-mRNA ISH, positivity for EBER was detected in rare stomal lymphocytes but not the overlying epithelium in the inverted SNP with SCC. The remaining cases, including the other inverted SNP positive for EBV by PCR, were completely negative by both ISH techniques. Human papillomavirus was detected by ISH in 1 of 19 (5%) inverted, 1 of 1 (100%) inverted with squamous cancer, 5 of 5 (100%) fungiform, and 0 of 3 (0%) oncocytic SNP. Three SNP contained HPV 6 (all fungiform), three SNP labeled for HPV 11 (two fungiform and the inverted SNP with squamous cancer), and one inverted SNP contained HPV 16. Of the five fungiform SNP, four showed foci of koilocytosis. The results indicate that EBV is not present in sinonasal papillomas. The presence of EBV positive stromal lymphocytes in these lesions may account for a proportion of PCR-positive cases. Oncocytic SNP are unassociated with HPV, whereas inverted SNP contain HPV in a minority of cases. In contrast, fungiform SNP are consistently associated with HPV types 6 and 11 and usually show histologic evidence of viral infection.

Detection of Kaposi's sarcoma-associated herpesvirus-like DNA sequence in angiosarcoma.

The partial DNA sequence of a putative new herpesvirus has recently been isolated from almost all cases of Kaposi's sarcoma (KS), from a small subset of AIDS-related lymphomas, and from a high proportion of multicentric Castleman's disease. The presence of this KS-associated herpesvirus, which is also known as human herpes virus 8 (KSHV/ HHV8), has not been reported in vascular tumors other than KS. We therefore examined a series of vascular neoplasms of both endothelial and pericyte derivation using polymerase chain reaction to detect a 233-hp segment of the viral DNA. KSHV/HHV8 sequences were found in 7 of 24 (29%) angiosarcomas and 1 of 20 (5%) hemangiomas but not in any hemangiopericytomas (0 of 6). The presence of the virus in angiosarcoma was confirmed by direct sequencing of the polymerase chain reaction product and Southern blotting in one case each. Only one of the affected patients was known to be immunocompromised. By detecting its presence in a significant proportion of angiosarcomas, this study extends the number of tumors associated with KSHV/HHV8, further tightens its association with malignancy, and suggests a tropism of the virus for endothelial cells. The presence of KSHV/HHV8 in angiosarcomas in addition to classical KS also indicates that immunosuppression is not a requisite for viral infection.