Evolutionary origin of eukaryotic cells.

This article reviews literature on the transition from rudimentary prokaryotic life to eukaryotes. An overview of the differences between these organisms and theories of eukaryogenesis are reviewed. Various methods of investigating the transformation from prokaryotes to eukaryotes are elaborated, including the fossil, the molecular and living records, and examples are given. Lastly, the recent molecular studies and the impact on phylogenetic classification for the tree of life, based on molecular evolution, are discussed.

Tenascin-C expression in ultrastructurally defined angiogenic and vasculogenic lesions.

Tenascin-C (TN) is an extracellular matrix glycoprotein expressed during embryogenesis. Its distribution is restricted in normal adult tissues and is upregulated in tumors and inflammatory conditions. Twenty-five specimens were studied, including 7 reactive vascular lesions (6 cases of granulation tissue and 1 case of bacillary angiomatosis), and 18 vascular tumors (6 angiosarcomas, 7 hemangioendotheliomas, and 5 AIDS-related nodular type Kaposi's sarcomas). Formalin fixed-paraffin-embedded tissues were stained with monoclonal antibody to TN (DAKO) and with MIB-1 (AMAC). Heterogeneous expression of TN immunoreactivity was seen in all cases, with a diffuse pattern in bacillary angiomatosis and most granulation tissue cases and a focal pattern in angiosarcoma and most hemangioendothelioma cases. Kaposi's sarcoma cases showed both a focal and diffuse pattern of distribution. In most cases proliferation indices (PI) did not correlate with TN expression. Electron microscopy demonstrated active angiogenesis in bacillary angiomatosis and granulation tissue and vasculogenesis in angiosarcoma and hemangioendothelioma. The study demonstrated positive TN expression in reactive lesions with angiogenesis (granulation tissue and bacillary angiomatosis) and neoplastic lesions showing vasculogenesis (angiosarcoma and hemangioendothelioma), although with a different pattern of distribution. These results suggest that TN might be an important extracellular matrix glycoprotein in angiogenesis and vasculogenesis.

Tenascin expression in astrocytomas correlates with angiogenesis.

We investigated the expression and distribution of the extracellular matrix protein tenascin (TN) in 59 astrocytomas and 11 samples of normal brain by Western blot analysis and immunohistochemistry using antibodies against human TN. The tumors included 14 juvenile pilocytic astrocytomas (grade 1), 13 low grade fibrillary astrocytomas (grade II), 8 anaplastic astrocytomas (grade III), and 24 glioblastomas multiforme (grade IV). Proliferation indices were calculated by computer-based image analysis after immunostaining with the MIB-1 antibody against the Ki-67 proliferation-associated antigen. Western blot analysis for TN on fresh frozen tumor tissue from 23 of the 59 astrocytomas indicated up to 4-fold higher TN expression in glioblastomas multiforme than in nontumorous control tissues. Enhanced intercellular expression of TN was observed by immunohistochemistry in glioblastomas multiforme. More-over, TN immunostaining was consistently greater within and around the walls of hyperplastic blood vessels than nonhyperplastic vessels of both high grade tumors and juvenile pilocytic astrocytomas. Juvenile pilocytic astrocytomas with increased TN expression by Western blot analysis had vascular hyperplasia by light microscopy. Proliferation indices moderately correlated with tumor grade. Enhanced immunohistochemical expression of TN was associated with higher tumor grade with higher proliferation indices. The strong association of TN and vascular hyperplasia, regardless of tumor grade, suggests that TN may play a crucial role in angiogenesis.

Angiogenic process in bacillary angiomatosis.

Eight cases of cutaneous bacillary angiomatosis related to acquired immunodeficiency syndrome were studied by light and electron microscopy and by immunohistochemistry with a panel of antibodies specific for endothelial and histiocytic markers. Light microscopy showed an inflammatory reaction with florid neovascularization and clusters of Warthin-Starry-positive bacilli. In addition, solid areas of spindle cells were also present that in some cases mimicked Kaposi's sarcoma or other sarcomas. The investigation focused primarily on the spindle cell areas and the angiogenic process present in bacillary angiomatosis. By immunohistochemistry the lesions, including the spindle cell areas, expressed all endothelial markers used; CD34, factor VIII-related antigen, and Ulex europaeus 1 were the most consistent in intensity, however. In those areas the other endothelial markers, BNH9 and Psophocarpus tetragonolobus, were weak and not always uniform. The macrophage/monocyte markers used were alpha 1-antitrypsin, lysosome, kp1 (CD68), and polyclonal factor XIIIa; these revealed a sprinkle of positive cells ranging from 10% to 20% of the cell population. By electron microscopy primitive capillaries were present lined by plump endothelial cells containing frequent abluminal microprocesses forming intercellular lumina. Mitoses and intracytoplasmic lumen formation were infrequent. The study illustrates that bacillary angiomatosis is composed of active endothelial neoformation with the spindle cells representing immature endothelial cells. Furthermore, the features of this angiogenic process recapitulate the morphologic events described in experimental models.

Immunohistochemical and electron microscopic profiles of cutaneous Kaposi's sarcoma and bacillary angiomatosis.

Thirty cases of cutaneous Kaposi's sarcoma (KS) were evaluated and compared with eight cases of acquired immunodeficiency syndrome (AIDS)-related bacillary angiomatosis (BA). The morphologic features of both lesions were studied by light and electron microscopy and by immunohistochemistry with monoclonal endothelial antibodies against CD34, BNH9, and factor VIII-related antigen as well as the lectins Ulex europaeus 1 and Psophocarpus tetragonolobus. Macrophage/monocyte markers used were alpha 1-antitrypsin, lysosome, Kp1 (CD68), and polyclonal factor XIIIa. Electron microscopic studies demonstrated that most of the spindle cells in KS showed a paucity of cell organelles and an absence of Weibel-Palade bodies (WPB), whereas the cells in BA showed activated endothelial cells with WPB. By immunohistochemistry the spindle cells in KS were consistently positive for CD34 only, whereas proliferating cells in BA expressed all endothelial markers used. Numerous cells expressing macrophage/monocyte markers were present surrounding both KS and BA, and a small number of similar cells were entrapped within both lesions. The results demonstrated a restricted immunohistochemical profile for endothelial cell markers in spindle cells of KS (CD34+) distinct from that of endothelial cells in BA. These findings suggest that the spindle cells in KS are poorly differentiated endothelial cells or that they belong to an endothelial cell subset with partial expression of endothelial phenotype.

Development of vascular neoplasia in Castleman's disease. Report of seven cases.

Seven cases of vascular neoplasia arising within lesions of hypervascular follicular hyperplasia (HFH) fulfilling the criteria of Castleman's disease are described. The patients did not have evidence of acquired immunodeficiency syndrome or other immunologic disorders. The masses were solitary and located in the retroperitoneum (five cases), mediastinum (one case), and axilla (one case). Grossly, they measured up to 20 cm and had a variegated appearance. In each case two morphologically distinct processes were present: a mesenchymal spindle-cell neoplasm with evidence of vascular differentiation and Castleman's disease of hyaline vascular type. The two processes blended with each other, with the neoplasm appearing to be continuous with the interfollicular proliferation of small vessels that is typical of Castleman's disease. The lesions behaved aggressively in two cases, both patients having died with metastatic disease. This remarkable association may be viewed as a pathologic manifestation of the intimate functional relationship that exists between the immune and the vascular systems. Other probable examples of this relationship are systemic Castleman's disease associated with Kaposi's sarcoma, localized Castleman's disease associated with vascular hamartoma, histiocytoid hemangioma/angiolymphoid hyperplasia with eosinophilia, and (possibly) angiomatoid malignant fibrous histiocytoma. Perhaps these associations are mediated by the production of angiogenic factors by the activated lymphoid cells.

Tubuloreticular reorganization of cytomembranes in cells treated with human alpha interferons--a review.

Human alpha interferons (IFN-a) cause a reorganization of internal cell membranes into tubuloreticular inclusions (TRI). Morphogenesis and cytochemistry indicate a pre-Golgi intracisternal origin from the endoplasmic reticulum. Clinically, TRI formation in human blood mononuclear cells correlates with systemic IFN-a treatment or with endogenous overproduction of IFN-a in viral or autoimmune diseases (e.g., rubella syndrome, AIDS, systemic lupus erythematosus). In vitro, TRI formation can be produced by treatment of Daudi lymphoblasts or vascular endothelial cells with IFN-a, and is blocked by actinomycin-D. In Daudi lymphoblasts or vascular endothelial cell cultures, TRI formation parallels induction of 2'-5' A synthetase, inhibition of thymidine kinase and growth inhibition; however, heavy water treatment of Daudi cells prevented TRI formation while induction of 2'-5' A synthetase and growth inhibition persisted. TRI formation was dissociated from IFN-a antiproliferative activity in a mutant clone of Daudi lymphoblasts. Decreased glycoprotein biosynthesis and increased phospholipid biosynthesis may accompany progressive TRI accumulation.

Intracisternal tubules in a case of chronic lymphocytic leukaemia.

In a case of chronic lymphocytic leukaemia we found that a few (less than 5%) of the circulating leukaemic lymphocytes contained inclusions of a type which do not appear to have been reported in the literature. The inclusions presented as solitary tubules or aggregates of parallel tubules lying within dilated cisternae of the rough endoplasmic reticulum and the perinuclear cistern. Some of the tubules were bounded by a single wall, others by a double wall. We also found a tubule bounded by three walls and another where a segment of the tubular profile was triple-walled and the remainder double-walled. We are inclined to think that the walls of these tubules are composed of membranes. The aetiogenic agent or agents responsible for the production of intracisternal tubules and their mode of formation are obscure.

Cytomembranous inclusions observed in acquired immunodeficiency syndrome. Clinical and experimental review.

Two types of cytomembranous inclusions commonly occur in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related conditions: tubuloreticular inclusions (TRI) and cylindrical confronting cisternae (CCC). CLinical and experimental studies both indicate that the occurrence of TRI in AIDS, systemic lupus erythematosus, or viral infections is directly related to endogenous systemic or local elevations of type I interferons (interferons alpha or beta). Moreover, these inclusions develop in patients or rhesus monkeys undergoing interferon alpha treatment. Rarely had CCC been reported in human tissue before the AIDS epidemic, but they were well known to develop in the hepatocytes of chimpanzees after experimental inoculation with human non-A, non-B hepatitis agent. In AIDS, CCC frequently coexist with TRI, and their appearance is associated with disease progression. A relationship of CCC to type I interferons is indicated by recent in vitro investigations, but clinical discordances in their appearance of TRI, and CCC suggest some differences in their pathogenesis, possibly related to cellular susceptibility or etiologic cofactors.

Ultrastructural findings in the acquired immunodeficiency syndrome (AIDS).

Ultrastructural studies have made significant contributions in evaluating the pathology and pathogenesis of AIDS. Three distinct types of abnormal cytomembranous inclusions in tissue specimens or peripheral blood mononuclear cells from AIDS patients are described--vesicular rosettes (VR), tubuloreticular inclusions (TRI), and cylindrical confronting lamellae (CCL).

Interferon-related leukocyte inclusions in acquired immune deficiency syndrome: localization in T cells.

Blood samples from a series of 12 patients with Kaposi's sarcoma or infectious complications of the acquired immunodeficiency syndrome (AIDS) and from 18 homosexual contacts of AIDS patients were screened for interferon-related tubuloreticular inclusions (TRI) in circulating leukocytes. In the AIDS patients, TRI were detected by transmission electron microscopy in 1.5 to 10% of mononuclear cell sections. They were most frequent in patients with a decreased fraction of T helper cells and T4/T8 ratios less than 0.2. Only rare TRI-positive sections were found in 3/12 homosexual contacts with lymphadenopathy and 1/6 asymptomatic contacts. Serum interferon was found to be elevated in each AIDS case tested, but was not a sufficient condition for detection of TRI in homosexual contacts. Active DNA virus infections, including cytomegalovirus, were common to the AIDS cases and possibly contributed to the TRI pathogenesis. Localization of TRI in T suppressor/cytotoxic cells was demonstrated with monoclonal anti-Leu 2a antibodies. The pathophysiologic significance of interferon stimulation with formation of TRI in immunocompetent cells requires further investigation.

Disseminated tubuloreticular inclusions in acquired immunodeficiency syndrome (AIDS).

Tissue biopsies and peripheral blood samples from 10 patients with the characteristic clinical features of acquired immunodeficiency syndrome (AIDS) were examined by electron microscopy and ultracytochemical myeloperoxidase technique. Abundant tubuloreticular inclusions (TRI) were detected within the endoplasmic reticulum of capillary endothelial cells, histiocytes, and lymphocytes in kidneys, small bowel, and lymph nodes, and lymphocytes and monocytes from peripheral blood. In general, TRI were found in the same type of cells and with conspicuous high frequency in our cases of AIDS as had been previously described in systemic lupus erythematosus (SLE). These findings indicate a morphologic link between these immunological disorders and the presence of TRI, raising the possibility of similar pathogenetic mechanisms.

Ultrastructural and immunoelectron microscopic studies of cells with abnormal cytoplasmic inclusions in patients with AIDS.

Nineteen specimens of peripheral blood mononuclear cells (PBMC) or biopsies of lymph nodes from patients with the acquired immunodeficiency syndrome (AIDS) were investigated ultrastructurally and by immunoelectron microscopy. Two main ultrastructural cytoplasmic inclusions were present in lymphoreticular cells: cylindrical confronting lamellae (CCL) and tubuloreticular inclusions (TRI). Furthermore their close ultrastructural association in the same cell was demonstrated for the first time. The percentage of PBMC sections bearing CCL was lower than the percentage of sections with TRI, except for one case of prodromal lymphadenopathy with risk factors for AIDS. The types of PBMC bearing inclusions were identified as T cells by immunoelectron microscopy. A relationship between the presence of TRI and plasma interferon levels is known but other unknown factor(s) are evidently involved in the morphogenesis of CCL.

Primary T-cell lymphoma of oral cavity.

Immunopathologic studies classify lymphoma under the T-cell or B-cell groups. Such a classification gives a better indication for prognosis and treatment of lymphomas, with the T-cell group having the worse prognosis. A patient with a T-cell lymphoma of the oral cavity is presented. The diagnostic features and management are discussed.

Synovial sarcoma: a clinical, pathological, and ultrastructural study of 26 cases supporting the recognition of a monophasic variant.

Twenty-six cases of synovial sarcoma (14 biphasic, 12 monophasic) were subjected to a clinicopathological study that included electron-microscopic examination of six tumors. Monophasic tumors were composed predominantly of uniform, densely packed, small spindle cells with scant cytoplasm identical to those of the "stromal" elements of typical biphasic tumors. The arrangement of these cells into narrow interlacing fascicles, forming tight whorls and showing little collagenization, was distinctive for this tumor. Major clinical differences between the two types of synovial sarcoma were the tendency for monophasic tumors to arise in distal extremity locations (seven of 10), and the poorer prognosis of monophasic tumors, 30% surviving 5 years compared to 58% for biphasic tumors. At the ultrastructural level, monophasic tumors and the spindle-cell components of biphasic tumors were identical. Both were composed of spindle or polygonal cells attached by numerous desmosomes. Prominent Golgi, abundant RER, perinuclear microfilaments, and glycogen aggregates were characteristic. Intercellular spaces containing elongated cytoplasmic filopodia were observed consistently, as were fragments of basement membrane-like material. The EM findings concur with those described previously in normal and pathologic synovium, and support a synovioblastic origin for the monophasic variant of synovial sarcoma.

Endocrine pancreatic tumors: ultrastructure.

Endocrine pancreatic tumors are frequently multicellular and produce several hormones and peptides. A review of the basic concepts of hormone secretion, pancreatic islet cell composition and ultrastructural make-up of tumors is presented. The importance of correlating ultrastructural, immunocytochemical and biochemical studies of these tumors is emphasized.

Epithelioid sarcoma: ultrastructural similarity to nodular synovitis.

The ultrastructure of nodular synovitis of the knee and epithelioid sarcoma of the hand are compared. Both lesions show a similar pattern of light and dark cells having filopodia and microvilli, an outer coat of finely granular matrix without well defined basal laminae, maculae adherentes and attachment sites, pinocytotic vesicles, cytoplasmic filaments and complex nuclear invaginations. These similarities suggest a common histogenesis and support the concept that the epithelioid sarcoma is derived from synovioblastic mesenchyme.

Angiosarcoma of the skin. A clinicopathologic and fine structural study.

A study of ten cutaneous angiosarcomas is presented. These tumors characteristically involve the scalp or face of elderly individuals, where they present as bluish or violaceous plaques and nodules. They have a marked tendency for local spread in surface and depth, and a third of them eventually give rise to distant metastases, particularly to cervical lymph nodes and lung. Microscopically, angiomatous areas of freely anastomosing channels lined by atypical endothelial cells are seen alternating with Kaposi-like spindle cell areas and undifferentiated foci. By electron microscopy, the tumor cells are seen to have all the features of endothelial cells, including pinocytotic vesicles, tubulated bodies, and in one case closed fenestrations. They also exhibit a cytoplasmic specialization here interpreted as the intracellular formation of a vascular lumen. Pericytes and cells resembling smooth muscle cells are also present. In the differential diagnosis this entity has to be distinguished from other clinical types of angiosarcoma of the skin and from a number of benign and malignant conditions. It is suggested that surgery be used for solitary, well circumscribed tumors and radiation therapy for tumors that either are multicentric or have ill defined margins.