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Abstract Thrombotic thrombocytopenia with severe depletion of plasma von Willebrand factor (vWF) was induced in normal large animals (5 dogs and 2 pigs) by botrocetin, a Bothrops factor requiring vWF for platelet agglutination. Botrocetin (90 to 100 U/kg, 2.14 to 2.38 mg/kg, in a single IV injection) reduced plasma vWF activity to

Currently, therapeutic platelet concentrates can be stored for only 5 days. We have developed a procedure that permits long-term storage of fixed and lyophilized platelets that retain hemostatic properties after rehydration. These rehydrated lyophilized platelets (RL platelets) restore hemostasis in thrombocytopenic rats and become incorporated in the hemostatic plug of bleeding time wounds of normal dogs as well as von Willebrand disease dogs with partially replenished plasma von Willebrand factor. Ultrastructurally, these platelets are well preserved and are comparable to control normal washed platelets. Flow cytometry analysis shows that RL platelets react with antibodies to the major surface receptors, glycoprotein (GP)Ib and GPIIb/IIIa. These receptors are involved in platelet agglutination, aggregation, and adhesion. In vitro functional tests document the ability of RL platelets to adhere to denuded subendothelium and to spread on a foreign surface. Circulating RL platelets participated in carotid arterial thrombus formation induced in normal canine subjects. The participation of RL platelets in these vital hemostatic properties suggests that with further development they could become a stable platelet product for transfusion.

Resveratrol (3,4′-trihydroxystilbene), a natural product is present in significant concentrations in red wine, peanuts, walnuts etc. Emerging evidence indicates that resveratrol exerts antitumorigenic activity in various tumor models including prostate. Although multiple biological effects on proliferation, apoptosis and activation of SIRT1 have been demonstrated to be associated with resveratrol-induced activities, the precise mechanism associated with resveratrol-induced SIRT1 activation and cancer cell growth inhibition remains unclear. In addition, whether resveratrol intervention suppresses the development and progression of PIN (Prostatic Intraepithelial Neoplasia) is unknown. In this study, we examined the role of SIRT1 and the underlying mechanism involved in resveratrol-mediated biological effects. Our results show that although resveratrol significantly inhibited proliferation of multiple prostate cell lines including RWPE-1, C42B, PC3 and DU145 at higher concentrations (> 50 µM); however, at lower concentrations (< 25 µM), resveratrol prompted cell proliferation. Interestingly androgen responsive LNCaP cells exhibited resistance to resveratrol-mediated inhibition of cell proliferation. Under these experimental conditions, we also observed significant increase in autophagy without remarkable increase in apoptosis. Given the role of Akt/mTOR signaling pathway as a negative regulator of autophagy, we investigated whether resveratrol induce autophagy via modulation of Akt/mTOR signaling. Our data indicate that resveratrol-induced autophagy was associated with decreased levels of mTORC1 activity and increased SIRT1 expression. Knockdown of SIRT1 enhanced prostate cell proliferation and attenuated resveratrol-induced autophagy. Using prostate specific PTEN−/− mice, we found that dietary administration of resveratrol reduced the incidence of high-grade PIN lesions significantly. These findings implicated an important role for mTORC1/SIRT1 signaling axis in mediating resveratrol-induced upregulation of autophagy and inhibition of apoptosis. [Supported by NIH CA137578 (APK)] Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2585. doi:1538-7445.AM2012-2585

Apolipoprotein E-deficient mice have spontaneous elevations of total plasma cholesterol and triglycerides and reduced high-density lipoprotein. The mice develop arterial lesions in a time-dependent manner. Lesional distribution was centered in the aortic sinus in young mice, and the lesions were widely distributed throughout the arterial tree in mice at 8 to 9 months of age. In young mice, subendothelial foam cell deposits were present in the aortic sinus adjacent to valve-attachment sites. By 5 months of age, foam cell deposits, free cholesterol, and admixed smooth muscle cells composed the developing atherosclerotic lesions. After 8 to 9 months of age, the arterial lesions showed increased complexity, and fibrous cap lesions were present. Transmission electron microscopy showed foam cells, smooth muscle cells (both contractile and synthetic varieties), cellular debris, and acicular cholesterol deposits within the plaques. By scanning electron microscopy, subendothelial collections of foam cells were present within the aortic sinus and ascending aorta. The results show that the complexity of the atherosclerotic lesions that develop in these apo E deficient-mice are similar to those described in other species and therefore represent an important model for studies of genetic and environmental influences on the atherosclerotic process.

The consequences of the lack of apolipoprotein A-I (apoA-I) were evaluated in mice made to lack apoA-I by gene targeting. Inbred strain 129 mice homozygous for the inactive Apoa1 gene and maintained on regular mouse chow had markedly reduced total cholesterol (26% normal) and high-density lipoprotein (HDL) cholesterol (25% normal) levels in their plasma. Their plasma lipoproteins lacked apoA-I and were reduced in all other apolipoproteins but apoE. ApoE comprises about one third of the protein of HDL particles in homozygotes, whereas it is present in only trace amounts in normal HDL. Despite the reduction of HDL cholesterol, no atherosclerotic lesions were observed in any of the homozygous mice evaluated (up to 15 months of age). After being maintained on an atherogenic diet for 4 weeks, total plasma cholesterol of the homozygous mutants increased by 20 mg/dL, while that of normals increased by 60 mg/dL. Mice with mixed 129 and C57BL/6J genetic backgrounds were fed the atherogenic diet for 20 weeks. A small number of foam cells were found attached to the aortic surface in some of the animals, but the extent and occurrence of these depositions were not related to the apoA-I genotype. Our results demonstrate that a lack of apoA-I does not by itself cause atherosclerosis in mice.

The pulmonary donor pool would increase substantially if lungs could be safely transplanted after cessation of circulation. To determine whether ventilation of cadaver lungs could improve graft function, canine donors were sacrificed and then ventilated with 100% oxygen (n = 6) or 100% nitrogen (n = 6); 6 served as nonventilated controls. Four hours after death, the lungs were flushed with modified Euro-Collins solution and harvested. Controls were ventilated with 100% oxygen only during flush and harvest. Recipients were rendered dependent on the transplanted lung by occlusion of the right pulmonary artery and bronchus 1 hour after transplantation. Ventilation was maintained at a constant inspired oxygen fraction of 0.4. Four controls died of pulmonary edema shortly after occlusion of the native lung. The mean arterial oxygen tensions in the oxygen-ventilated, nitrogen-ventilated, and control groups at the end of 8 hours were 81 mm Hg (n = 4), 88 mm Hg (n = 3), and 55 mm Hg (n = 2), respectively. Postmortem oxygen ventilation improved early recipient survival and gas exchange. Postmortem nitrogen ventilation improved early gas exchange and delayed recipient death compared with nonventilated controls. The mechanics of ventilation appears to confer a functional advantage independent of a continued supply of oxygen. Transplantation of lungs harvested from cadavers after cessation of circulation might be feasible.

To explore and develop protocols for drying blood platelet preparations for extended storage without undue compromise of hemostatic function or cell integrity upon rehydration. A successful project outcome would greatly facilitate the use of platelets in the medical support of combat casualties with severe blood loss, major surgical repair, or extensive burn injury. The three collaborating performance sites are bringing together expertise in cell stabilization techniques and platelet function testing both in vitro and in vivo. The ultimate goal is to identify a practical procedure to produce a stabilized platelet preparation that can be stored virtually indefinitely while maintaining transfusion efficacy. Such a product would also be useful in civilian blood banking. The third year of this grant saw advancement of the animal model studies testing the hemostatic capabilities and circulatory survival of dried platelets stabilized with paraformaldehyde, refinement of an alternative platelet stabilization method using permanganate and trehalose, and an initial study of dried RBC in an in vivo circulatory model. In normal canine experimental subjects, rehydrated canine platelets were found in circulation for at least 24 hours after infusion; similar results were obtained in bleeder pigs (a congenital strain with von Willebrand's disease). Rehydrated platelets were shown to adhere to subendothelium in situ when the animal subjects were exposed to a vessel stenosis and injury protocol or subjected to a bleeding time test.

The biological behavior of pleomorphic adenomas (mixed tumors) of salivary gland origin is complex. Tumors with benign histologic features may exhibit recurrence and locally aggressive behavior especially after incomplete excision. A small percentage of pleomorphic adenomas have obvious malignant components in epithelial or in both epithelial and mesenchymal components and can metastasize. There are also rare case reports which appear to document typical pleomorphic adenomas of salivary gland with histologically identical visceral and lymph node metastases. Recently myoepithelial cell proliferation has been identified as a possible predictor of aggressive clinical behavior in otherwise histologically benign pleomorphic adenomas. We report such a parotid gland lesion with local recurrence and retroperitoneal spread. DNA-flow cytometry of cells from the paraffin-embedded primary and metastasis showed similar aneuploid populations. Aneuploidy appeared to reflect the malignant potential of this particular pleomorphic adenoma and suggests that DNA-flow cytometry of salivary gland tumors may yield important prognostic information.

The thrombogenic potential of atherosclerotic diet-induced coronary atherosclerotic plaques was investigated in normal swine and in bleeder swine with homozygous von Willebrand disease. Fourteen paired normal and bleeder swine were placed on a 1% cholesterol diet for 1 to 16 weeks. Serum cholesterol was elevated in all animals at sacrifice. Foam cell deposits developed in all major epicardial coronary arteries, and lesions progressed over time from small subendothelial foam cell deposits to fibrous cap lesions that contained foam cells, elastic fibers, collagen, degenerative material, and smooth muscle cells. Balloon catheter injury resulted in platelet deposition, largely in a monolayer or as small platelet clumps devoid of fibrin. Lipid debris was present in injured areas of the subendothelium but did not induce thrombus formation. When the injury involved the media, platelet-fibrin thrombi were formed. Lipid was not present in these thrombi. Morphometric analysis of platelet deposition on ballooned atherosclerotic vessels showed similar numbers of platelets in both phenotypes. However, the attached platelets in bleeder pigs showed significantly less spreading than did those in the normal animals. The results show that injury to intimal foam cell and mixed cellular lesions in coronary arteries of cholesterol-fed swine does not promote the development of platelet-fibrin thrombus formation. In contrast, when the injury extended to the media, mixed thrombi were formed.

A review was undertaken of the clinical, gross, and microscopic features of thyroid carcinoma in all patients younger than 21 years of age seen at North Carolina Memorial Hospital from 1952 to 1987 (N = 32). These patients had papillary carcinoma, well-differentiated follicular carcinoma with Hurthle cell change, medullary carcinoma, and an unclassifiable aggressive malignancy. In spite of the presence of lymph node metastases at diagnosis in more half the patients with papillary carcinoma, the prognosis of pediatric papillary thyroid carcinoma appears to be excellent with treatment by surgical debulking and hormonal thyroid suppression. Flow cytometric study of 26 cases showed tumor aneuploidy in 8 of 21 papillary carcinomas and 2 of 3 follicular carcinomas. Aneuploidy did not, however, correlate with clinical outcome in this group of pediatric patients, who were followed for 1 to 29 years. Analysis of multiple tissue blocks of tumor does appear to increase the probability of identifying aneuploid populations.

A patient with recurrent Sertoli-Leydig cell tumor is described. The light and ultrastructural findings are illustrated. The tumor recurred first as a poorly differentiated tumor with rhabdomyoblastic differentiation. Following chemotherapy the next recurrence exhibited well differentiated Sertoli-Leydig cell elements. These findings may reflect the capability of this tumor type to undergo chemotherapeutic transformation similar to the transformation which has been described in germ cell tumors of the ovary and testis. This observation may be of importance in the clinical management of patients with poorly differentiated Sertoli-Leydig cell tumors.

A patient with a nodular lymphoma morphologically indistinguishable from follicular B-cell lymphoma subsequently developed a diffuse T-cell lymphoma. This T-cell lymphoma displayed characteristics analogous to mature T-lymphocytes, and typed as a suppressor/cytotoxic T-cell with the monoclonal antibodies. The light and electron microscopy morphology of the T-cell lymphoma was similar to that reported for node-based T-cell lymphomas. There was a polymorphous proliferation of variably transformed lymphocytes including immunoblasts. This case could represent either a nodular form of T-cell lymphoma converting to a diffuse T-cell lymphoma, or a follicular B-cell lymphoma preceding, and possibly inducing, a suppressor T-cell lymphoma.

Multinucleated, foreign body giant cells were formed by the fusion of blood monocytes on polymeric membranes perfused with blood during extended extracorporeal circulation. In the current study, heparinized blood, flowing in an arteriovenous shunt in a sheep, perfused polycarbonate, polypropylene and silicone rubber membranes of a recently developed bioartificial tissue culture system. The multinucleated giant cells were studied by light, scanning electron, and transmission electron microscopy, after membrane perfusion for periods of one to two weeks. The giant cells, which were the predominant cellular components of the blood-polymer interface layer, contained from a few to more that one hundred nuclei and varied in diameter up to 400 microns. The cellular interaction with the three membrane types was similar, although fewer mononuclear cells were observed adhering to the silicone rubber membrane. The presence or absence of micropores in the membranes had no effect on the formation of giant cells, nor did the presence of foreign tissue in culture behind the microporous membranes. High blood flow rates and chronic anticoagulation with heparin permitted observation of this foreign body reaction of blood independent of thrombosis.

The clinical course of a 17-year-old boy with primary osteogenic sarcoma of the left atrium with partial obstruction of the mitral valve and the right pulmonary veins is described. After operative removal of the tumor, echocardiography documented its rapid recurrence. Despite two subsequent open-heart operations and adjuvant chemotherapy and radiotherapy, the patient died twenty-one months after the initial symptoms. Previous reports of such tumors are reviewed, and technical difficulties of removal are discussed.

This study was designed to examine the functional characteristics of thyroid adenomas, adenomatous (colloid) nodules, hyperfunctioning nodules, and normal thyroid parenchyma with respect to the presence of TSH receptors, levels of adenylate cyclase, and the responsiveness of adenylate cyclase to specific stimuli, e.g., NaF (sodium fluoride), GTPγS [guanosine 5′-0-(3-thiotriphosphatate)], PGE1, and TSH. Aliquots of specimens from patients undergoing thyroidectomy [11 normal thyroids, 7 adenomas, 8 adenomatous (colloid) nodules, 5 hyperfunctioning nodules] were immersed in liquid nitrogen and stored at 90°C. Studies were performed on partially purified plasma membranes. Receptor binding of125I-TSH was quantitated and analyzed according to Scatchard. Adenylate cyclase activity was assayed in the same tissue fraction by conversion of (α-32P) ATP to cAMP.

The early response to coronary artery injury was investigated in normal swine and in swine with von Willebrand disease (vWD). Thirty minutes after coronary endothelial denudation, a monolayer of platelets was adherent to areas of simple injury in both bleeder and normal swine. The number of adherent platelets was not significantly different in the two phenotypes. Injury involving the media of the vessel produced platelet-fibrin thrombi. Platelet activation, as judged by pseudopod formation and platelet spreading over areas of simple injury, was significantly less in bleeder animals than in normal animals. These studies suggest that chemotaxis and initial contact adhesion of platelets to injured arterial wall is independent of the von Willebrand factor. On the other hand, the spreading and activation of platelets on the subendothelium appear to be dependent on the presence of plasma von Willebrand factor. Through this mechanism von Willebrand factor may contribute to arterial thrombosis and atherogenesis.

Ultrastructural study of three parosteal osteogenic sarcomas showed this type of tumor to contain numerous myofibroblasts. These cells were admixed with occasional cells resembling osteoblasts and fibroblasts. Cartilaginous areas showed the typical arrangement of cartilage cells embedded in a dense collagen matrix. Ultrastructural examination of a recurrent lesion revealed the presence of numerous undifferentiated cells as well as the types of cells just described. In addition, desmosomes were evident between the more undifferentiated cells. The ultrastructural study of these tumors shows that parosteal osteogenic sarcomas are ultrastructurally as distinctive type of osteogenic sarcoma.

A comparative ultrastructural analysis of malignant soft tissue tumors (malignant fibrous histiocytoma, pleomorphic liposarcoma, and pleomorphic rhabdomyosarcoma) revealed similar ultrastructural features in this group of tumors. However, by electron microscopy these tumors can be differentiated on the basis of cytoplasmic and extracytoplasmic features (myosin filaments, lipid droplests and perinuclear intermediate filaments, for example). This is even true of less well differentiated tumors and tumor cells. These findings support and amplify the concept of a common histogenesis for tumors of mesenchymal origin. Paradoxical features observed by light microscopy wasrant further study by electron microscopy if the correct diagnosis is to be made in atypical cases, such as apparent malignant fibrous histiocytoma with cross striations.

A 71-year-old woman who presented with severe vaginal bleeding was found to have a uterine angiosarcoma after total abdominal hysterectomy and bilateral salpingo-oophorectomy. The diagnosis was confirmed by immunohistochemical studies that showed positive staining of tumor cells for factor VIII-related antigen and by ultrastructural studies revealing vasoformative structures surrounded by a thin basal lamina. Primary vascular tumors of the uterus are rare. The existence of malignant vascular neoplasms of the uterus has been questioned, and at most nine previously reported cases have been generally accepted as valid examples of uterine angiosarcoma. Based on those cases, the prognosis of uterine angiosarcoma is poor. Our studies demonstrate that angiosarcoma does occur in the uterus. Our patient is presently alive with recurrent disease.

A 33-year-old woman presenting with secondary amenorrhea and galactorrhea was found to have a Sertoli cell tumor of the ovary. The neoplasm also had a sex cord tumor with annular tubules (SCTAT) component. Further investigations revealed that in many respects the patient was endocrinologically pregnant. She had markedly elevated serum estrogen and progesterone levels and the endometrium demonstrated pronounced decidualization, but there was no evidence of actual pregnancy. Estrogen and progesterone were demonstrated by immunohistochemistry to be present in both the Sertoli cell and SCTAT portions of the tumor.

The proliferative response of medial smooth muscle cells to balloon-induced endothelial denudation was measured in coronary arteries of normal and von Willebrand's disease swine, a strain of swine with a genetic defect affecting platelet-vessel wall interactions. Animals were sacrificed 48 hours following endothelial injury. Incorporation of a 1-hour pulse label of 3H-thymidine was determined by measuring DNA specific activity. Autoradiography of coronary artery step segments was also performed. The ratio of DNA specific activity in ballooned vessels to that in nonballooned vessels ranged from 1.2 to 26.2. No statistically significant difference in 3H-thymidine incorporation between the two phenotypes was documented (p greater than 0.25). Similarly, DNA incorporation of 3H-thymidine as determined by autoradiography was accelerated to the same degree in ballooned vessels in both phenotypes. The results suggest that von Willebrand factor-mediated platelet activation is not essential for the release of platelet-derived growth factor or that in vivo factors other than platelet-derived growth factor play a significant role in the response of medial smooth muscle cells to acute intimal injury causing endothelial denudation.

Ultrastructural examination of 26 osteogenic sarcomas has revealed that in addition to the basic osteoblast comprising the tumor, five additional cell types may be identified. These include chondroblasts, osteocytes, undifferentiated cells and myofibroblasts. The latter cell type has not been reported in previous studies of medullary osteosarcomas. The relative portions of the cell types varied as to the type of osteogenic sarcoma studied. Osteoid production, the single diagnostic feature of these tumors, was evident and the various ultrastructural appearances of this material are shown. One case of an osteogenic sarcoma that arose in Paget's disease of bone is described and did not differ ultrastructurally from the conventional medullary osteogenic sarcoma. Our studies have shown that osteogenic sarcoma may share common ultrastructural features with other sarcomas involving bone and soft tissue and that the basic difference between osteogenic sarcoma and soft-tissue sarcomas is the presence of osteoid in the former and differing cytoplasmic differentiation in the latter category of tumors.

A case of a pure heterologous sarcoma of the uterine corpus composed exclusively of rhabdomyosarcomatous elements has been studied by multiple morphologic and biochemical techniques. The neoplasm filled the endometrial cavity and protruded out the cervical os, but the myometrium was only superficially invaded. The tumor did not extend outside the corpus. The pathologic features are discussed in detail. Evidence of striated muscle differentiation could be identified on light microscopic and ultrastructural examination. Immunoperoxidase staining of tumor cells with antibodies to myoglobin were positive. Histochemical preparations for lactate dehydrogenase, succinic dehydrogenase, and acid phosphatase were also positive in neoplastic cells. Other stains gave equivocal or negative results. These findings are discussed in comparison with previous reports.

Primary malignant urethral neoplasms are unusual in women. Those of mixed histologic type are so rare as to define adequate documentation. We report the case of an elderly black woman with an urethral carcinoma which had features of a transitional cell carcinoma as well as clear cell adenocarcinoma. The histologic and ultrastructural features are presented and the histogenesis is discussed. Although the patient had both high grade and high stage disease and failed initially after external beam radiation therapy, she is alive and well, without evidence of recurrent disease, 19 months after anterior exenteration.

An ultrastructural study of three cases of hemangiopericytoma showed cells partially or completely enveloped by well-formed basement membrane and basement membrane-like material. The cells exhibited prominent cytoplasmic filaments, some showing dense body formation, interdigitating cytoplasmic processes, and pinocytotic vesicles. A review of the literature revealed only 19 other cases of hemangiopericytoma studied by electron microscopy, and these included seven cases of meningeal origin (“angioblastic meningioma”). The most consistent feature seen in all but two cases was the presence of a basal lamina or basal lamina-like material either partially or completely surrounding tumor cells and separating endothelial cells from pericytes. The light microscopic diagnosis of hemangiopericytoma is difficult, and there is a tendency to append the diagnosis to a variety of other tumors with a prominent vascular pattern in which other specific diagnoses are not immediately evident. The presence, ultrastructurally, of well-developed basement membrane, myogenic type filaments, and pinocytotic vesicles in a tumor with light microscopic features suggestive of hemangiopericytoma would consolidate the diagnosis and usually eliminate diagnostic uncertainty. Cancer 47:906–914, 1981.

Solitary schwannomas arising in the juxtadrenal region are exceedingly rare. A middle-aged woman with a confusing clinical course was found to have a solid periadrenal mass, which was surgically excised. The gross and light microscopic appearance of the tumor was suggestive but not diagnostic of this entity. However, electron microscopic evaluation of the neoplasm revealed prominent basal lamina and interdigitating cellular processes characteristic of a schwannoma. The diagnosis of schwannoma was further supported by the demonstration of S-100 protein, type IV (basement membrane) collagen, and laminin immunoreactivity by immunohistochemical techniques. The use of these special studies to arrive at the diagnosis in this case and in the larger context in the diagnosis of rare adrenal and periadrenal tumors of uncertain origin is fully discussed.

The presence of a precipitating antibody to an extractable nuclear antigen, termed Ha, was examined by immunodiffusion in gel in three subpopulations of patients with Sjogren's syndrome (SS): (1) those with sicca complex alone, (2) those with SS and rheumatoid arthritis (SS-RA) and (3) those with SS and systemic lupus erythematosus (SS-SLE). Control populations included patients with rheumatoid arthritis (RA) alone and systemic lupus erythematosus (SLE) alone, and normal age-matched blood donors without a history of SS or other connective tissue disease. The results demonstrate the high incidence of anti-Ha antibody in sicca complex (68 per cent) versus the low incidence of the antibody in SS-RA (5 per cent) (p No correlations were found between anti-Ha antibody positivity and clinical parameters, such as serum immunoglobulin concentration, degree of abnormality of parotid scan, titer of rheumatoid factor or focal score of labial biopsy in the patients with SS. However, a correlation between anti-Ha antibody titer and clinical disease activity was noted in two patients examined. The appearance of the anti-Ha antibody was correlated with the development of pseudolymphoma in a third patient. The presence of the anti-Ha antibody may identify a subpopulation of patients with SS at greater risk of rapid progression of the disease and/or the development of pseudolymphoma.

The extent of coronary and aortic atherosclerosis was examined in pigs following balloon-catheter injury of coronary arteries and subsequent feeding of an atherogenic diet for 4 months. The pigs were either exposed intermittently to 100 ppm carbon monoxide or to ambient air alone. Three types of pigs were used: normals, homozygotes for von Willebrand's disease (bleeders), and heterozygotes (carriers). The 3 types of pigs developed coronary artery intimal lesions of similar thickness. Aortic lesions, quantified as percent of aortic surface involved with sudanophilia and raised fibrous plaques, were slightly less extensive in bleeder pigs than in normals. Carbon monoxide exposure did not increase the thickness of coronary artery intimal lesions, nor did it increase the percent of aortic surface involved with sudanophilia or raised fibrous lesions. These results suggest that exposure to low levels of carbon monoxide does not perceptibly enhance atherogenesis induced by hypercholesterolemia. None of 14 bleeder pigs showed evidence of myocardial infarction, despite significant coronary artery narrowing. Of the 24 normal and carrier pigs, 5 showed myocardial infarction. Four of these 5 pigs were exposed to carbon monoxide, while 1 was not exposed. These findings suggest that exposure to low levels of carbon monoxide may increase the incidence of myocardial infarction and that the absence of von Willebrand factor may be protective.

A 26-year-old man with lymphomatoid granulomatosis (LYG) was found at postmortem examination to have an immunoblastic sarcoma involving the central nervous system. Residual evidence of LYG was present only in the lungs at autopsy. Studies for intracellular immunoglobulin utilizing the immunoperoxidase technique showed a marked polyclonal reaction in sections of lymph nodes and occasional cells in the cellular central nervous system tumor that stained for intracellular immunoglobulins (IgG, IgM and both kappa and lambda). This case may represent another example of immunoblastic sarcoma occurring in the presence of an abnormal immune state or proliferation.

Properties of filled n-butyl-α-cyanoacrylates were studied as a function of filler-monomer ratio, time, and curing conditions. Matrix characteristics were determined on amine initiated bulk polymer. Calcium carbonate and mixtures of zinc oxide and zinc phosphate formed reinforced materials with low solubility and disintegration.

A 22-year-old woman developed breast cancer 15 years after radiotherapy to the lung for metastatic Wilms' tumor. Her 32-year-old mother died of bilateral breast cancer, suggesting a genetic predisposition to radiogenic cancer. Recent improvements in the survival of children with certain cancers necessitate long-term surveillance for iatrogenic neoplasia, particularly when familial susceptibility is evident.

A middle-aged woman presented with a pelvic mass. Pathologic examination of the resected specimen revealed a primary adenosquamous carcinoma of the left fallopian tube. Special studies supported the concept of the neoplastic cells differentiating along two major pathways, squamous cell carcinoma and mucin-producing adenocarcinoma.

• We observed the repair process of the choriocapillaris after confluent argon laser retinal photocoagulation in the domestic cat with a plastic injectioncorrosion technique coupled with scanning electron microscopy and transmission electron microscopy. Confluent photocoagulation was applied to the area of the retinal tapetum, creating two kinds of lesions: one consisted of five confluent burns and the other of 20 confluent burns. Specimens were prepared at 1, 30, and 60 days. Occlusion of the choriocapillaris was noted regardless of the length of time after photocoagulation. The only sign of repair was noted at 60 days when the choriocapillaris located at the edge of the lesion showed a uniform rearrangement. Transmission electron microscopy revealed severe damage to the endothelial cells, with lack of cell activation and permanent capillary closure in the vessels of the lesion proper.

A murine monoclonal antibody (mAb) against porcine von Willebrand factor (vWF) induced an antithrombotic state in normal pigs. Thrombosis was induced by a standard procedure of stenosis and mechanical injury of the artery. The mAb was an IgG1 kappa that inhibited vWF-induced platelet aggregation at a titer of 1:6250 and bound to immobilized vWF at a maximal dilution of 1:512,000. The antibody did not affect two other vWF functions, platelet adhesion and binding of coagulant factor VIII (factor VIII:C). The antithrombotic state was characterized by a prolonged bleeding time and lack of plasma vWF activity, but with near-normal levels of factor VIII:C and von Willebrand antigen. The circulating Ag.mAb complex demonstrated a multimeric distribution comparable to that of native plasma vWF. Three groups of pigs were studied: group A consisted of nine untreated animals, eight of which developed occlusive coronary thrombosis; group B, four treated animals with a long bleeding time, none of which developed occlusive thrombosis; and group C, two animals with preexisting thrombosis treated with mAb, in which stable blood flow was reestablished. Morphologically, the group B animals showed adherent platelets covering the injured intima but no thrombosis. This mAb is an antithrombotic agent that prevents platelet thrombosis without affecting intrinsic platelet function.

LYMPH-node enlargement occurs in approximately half of all patients with systemic lupus erythematosus.1 Although the histologic characteristics were described by Short2 in 1907, until 1943, lymphad...

Lymphoma presenting in bone (that is "reticulum cell sarcoma of bone") is a form of extranodal lymphoma historically described as frequently localized (this is, stage IE or stage IIE). Between 1970 and 1975, 14 patients with this entity were seen at the National Cancer Institute. This group had a variety of histologic subtypes of diffuse lymphoma. Thorough staging showed extensive disease (stage IV) in 12 of these patients (86%). In 10 of these the metastatic disease was unsuspected clinically. Seven patients achieved complete remissions after treatment was combination chemotherapy alone (two patients), irradiation alone (one patient), surgery alone (one patient), and both chemotherapy and irradiation (three patients) and are alive and free of disease 11 + to 70 + months after diagnosis. The other seven patients did not achieve complete remission status and have all died. Although lymphomas presenting in bone may occasionally be localized, careful staging in this series frequently showed extensive disease and altered the therapeutic approach.

Von Willebrand's disease protects pigs from developing cyclic or permanent coronary thrombosis (C/P-Th) following experimentally induced stenosis and injury (S/I) in an open chest anesthetized pig (Nichols et al, Circ Res., 1986; 59:1526). To confirm that this protection is related specifically to absence of von Willebrand factor (vWF), an IgG kappa monoclonal antibody (MAb) to purified porcine vWF was produced in mice. MAb inhibited platelet aggregation by ristocetin and botrocetin, but not ADP, thrombin, or collagen. MAb was infused into seven normal pigs. Bleeding times (BT) in all pigs were prolonged to >10 min, and platelet agglutinating factor levels as a measure of vWF activity were

Squamous metaplasia in the breast is rare. This case of an intracystic papilloma of the breast with prominent squamous change was found by electron microscopy and immunohistochemistry to contain evidence of squamous differentiation within myoepithelial cells. The findings suggest that squamous metaplasia of the breast may result from myoepithelial cell differentiation in a manner analogous to the development of squamous lesions in the cervix and salivary gland. The possible relationship of this finding to the development of squamous lesions of the breast is discussed.

The stromal cells of three cystosarcoma phyllodes, five typical fibroadenomas, and one juvenile fibroadenoma were studied by light and electron microscopy. Immunohistochemical staining for the S-100 protein also was performed on tissues from each of the three categories. On ultrastructural examination, cells comprising the three varieties of lesions were similar. Cells with fibroblastic features predominated in all cases. Myoid differentiation was present in two cases, one of cystosarcoma and one of fibroadenoma. Junctional complexes were present in the cystosarcomas but not in the fibroadenomas. Basal lamina was focally present around stromal cells in the cystosarcoma phyllodes but was not evident around cells of the typical fibroadenomas or the juvenile fibroadenoma. Stromal cells of the fibroadenomas and the cystosarcoma phyllodes did not stain for S-100 protein. The results support the hypothesis that the proliferating cells in all three tumor categories are similar and have features of fibroblasts. The lack of staining for S-100 protein would suggest an origin different from the myoepithelia. The latter conclusion, however, must be interpreted with a degree of reservation as we have shown that not all myoepithelial cells stain with certain monoclonal antibodies directed against the alpha and beta chain of S-100 protein.

A case of malignant thymoma is presented. The electron microscopic (EM) findings of the lymphocyte—epithelial relationships were similar to these previously described. Utilizing specific monoclonal antibodies to differentiate thymocytes from T-lymphocytes, the small cell population with ultrastructural features of lymphoid cells consisted of true thymocytes rather than peripheral T-lymphocytes. The latter finding may prove to be of importance in differentiating thymomas from reactive or most neoplastic lymphocytic processes involving the thymus gland.