Effect of anisotropic strain on the crosshatch electrical activity in relaxed GeSi films.

The physical origin of the crosshatch electrical activity in relaxed GeSi films was studied using a near-field scanning optical microscope (NSOM). The contrast and patterns in the near-field photocurrent images depend on the polarization direction of the NSOM light. These results rule out composition nonuniformity, junction depth variation, and scanning artifacts as dominant sources of the contrast. Numerical calculations show that local changes in band structure due to strain fields of the misfit dislocations are responsible for the experimental observations.

Fluorescently detectable magnetic resonance imaging agents.

This report describes the synthesis, characterization, and in vivo testing of several bifunctional contrast-enhancing agents for optical and magnetic resonance imaging (MRI) of experimental animals. These new agents integrate the advantages of both techniques since they can be visualized simultaneously by light and MRI microscopy. Employing this strategy allows the same biological structures of a specimen to be studied at dramatically different resolutions and depths. The complexes possess a metal chelator for binding a paramagnetic ion, gadolinium (Gd3+), and a covalently attached fluorescent dye. The first class of complexes are low-molecular weight species that are composed of the macrocyclic tetraamine 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid (DOTA) as the metal-chelating ligand coupled to tetramethylrhodamine. The second class of MRI-enhancing agents are composed of high-molecular weight polymers that are membrane impermeable and once injected into a cell or cells are trapped inside. These complexes possess multiple copies of both the metal-chelator-diethylenetriaminepentaacetic acid (DTPA) and the tetramethylrhodamine attached to a macromolecular framework of either poly(D-lysine) (pdl) or dextran. Images acquired of single cells after injection with these bifunctional agents enabled us to follow the relative motions and reorganizations of different cell layers during amphibian gastrulation and neurulation in Xenopus laevis embryos.

The distribution of factor XIIIa-positive cells in the human fetus and placenta.

Immunohistochemical staining for factor XIIIa, a transglutaminase, revealed a variety of positively stained cells in human fetal tissues. Factor XIIIa-positive cells were most numerous in the dermis and connective tissues. Numerous large, stellate cells in placental villi, decidua, and chorionic membranes also expressed factor XIIIa at 7-9 weeks gestational age, before the onset of fetal hematopoiesis. There was heterogeneity in the staining for factor XIIIa in the early and late fetal tissues, in both rounded and in dendritic cells. In preparations of consecutive sections and in double-labelling experiments, some cells expressed both factor XIIIa and certain monocyte markers and were identified in close association with blood vessels and lymphoid organs in the late fetus and in the placental villi at the end of gestation. Other rounded and dendritic cells expressed factor XIIIa but not monocyte markers, and were found in adult and fetal connective tissues at all gestational ages. These results suggest that there are two factor XIIIa-positive cell populations. One population is present at all developmental stages, does not express monocyte markers, and probably differentiates in situ from primitive mesenchyme. The other population appears mainly after the onset of fetal hematopoiesis, coexpresses some monocyte markers, is HLA-DR positive and may be capable of antigen presentation.

Carcinogenesis in porokeratosis. Evidence for a role relating to chronic growth activation of keratinocytes.

Porokeratoses are known to give rise to squamous and basal cell carcinomas. In this study, we examined 15 lesions of porokeratosis immunohistochemically for evidence of aberrant keratinization using several markers of keratinocyte (KC) maturation and differentiation, including involucrin, filaggrin, cytokeratins, and the growth activation marker psi-3. The staining patterns obtained were compared with several non-premalignant parakeratotic skin lesions including psoriasis, pityriasis rosea, pityriasis rubra pilaris, irritated seborrheic keratosis, atopic dermatitis, seborrheic dermatitis, and verruca vulgaris. The centers of porokeratoses stained in a pattern identical to that observed in other premalignant keratinocytic lesions including actinic keratoses, recessive dystrophic epidermolysis bullosa, and nonhealing wounds. KCs beneath the cornoid lamella (CL) stained in a pattern similar to that observed in squamous cell carcinomas. KCs peripheral to the CL in the epidermis showed a normal staining pattern. The control non-premalignant parakeratotic lesions displayed a variety of staining patterns, but none showed a pattern identical to that observed in porokeratosis. The failure of KCs in porokeratoses to mature and differentiate normally may be related to the increased incidence of carcinomas associated with these lesions.

Relationship of factor XIIIa-positive dermal dendrocytes to Kaposi's sarcoma.

The histogenesis of Kaposi's sarcoma (KS) has been the subject of controversy, much of which has centered around whether the spindle cells of KS are derived from vascular endothelium or from lymphatics. Recently, some investigators have speculated that the spindle cells of KS are derived from dermal dendrocytes, a population of mononuclear dendritic cells normally present in the papillary and upper reticular dermis. These cells have been shown to proliferate in response to a variety of stimuli and have been reported to express the plasma proenzyme factor XIIIa. We examined immunohistochemically sections fixed in formaldehyde solution and embedded in paraffin from 20 tumor-stage, 15 patch-stage, and 15 plaque-stage lesions of KS with antibodies directed against factor XIIIa, factor VIII-related antigen, Ulex europaeus lectin, and LN3 (anti-HLA-DR) to investigate the relationship of dermal dendrocytes to KS in general and to try to clarify the histogenesis of this tumor. Our results revealed that the dermis of patch- and plaque-stage KS lesions contains an increased number of factor XIIIa-positive dermal dendrocytes compared with normal dermis and that some of these cells are spindle shaped. Many of the spindle cells in patch- and plaque-stage lesions of KS, however, are negative for factor XIIIa. The cells lining the slitlike spaces and some spindle-shaped cells in close proximity to the vascular spaces stain for factor VIII-related antigen and for Ulex europaeus lectin. LN3 labeled many cells resembling macrophages within the lesions and in papillary dermis. Less than 25% of the dendritic cells within the lesions and in the adjacent dermis expressed both factor XIIIa and LN3. Tumor-stage lesions showed focal but unequivocal staining of the spindle cells for factor VIII-related antigen and Ulex europaeus lectin. Tumor spindle cells were negative for factor XIIIa. Factor XIIIa-positive dendrocytes were plentiful in the uninvolved dermis and were aggregated around the periphery of the tumor nodules. The expression of factor VIII-related antigen and Ulex europaeus lectin by the spindle cells of nodular KS, and their lack of expression of factor XIIIa, suggests that the spindle-shaped tumor cells in all stages of KS are derived from endothelial cells and not from dermal dendrocytes. Dermal dendrocytes appear to undergo hyperplasia in response to KS of all stages. In patch- and early plaque-stage KS lesions, dermal dendrocytes are near factor VIII-related antigen-positive spindle cells and tumor vessels. The mechanism reactive dermal dendrocyte hyperplasia in KS remains obscure.

Fixed drug eruptions: evidence for a cytokine-mediated process.

Fixed drug eruptions (FDE) are immunologic reactions to drugs which produce erythematous plaques or blisters that characteristically recur at the same cutaneous sites with repeated antigenic challenges. While a detailed pathogenesis of these lesions remains obscure, T-lymphocyte infiltration has been documented repeatedly. In this study, we tried to determine if FDE were mediated, at least in part, by cytokines, such as gamma-interferon. We examined biopsies from 6 cases of clinically well-documented FDE with an HLA-DR antibody, LN3, and an antibody to gamma IP-10 (IP-10), a protein expressed by keratinocytes, monocytes, lymphocytes and endothelial cells following exposure to gamma-interferon. We found staining of the dermal lymphocytes with anti-HLA-DR antibody in all 6 cases examined. Keratinocytes and endothelial cells showed only focal staining at the antibody concentrations used. In addition, there was keratinocyte staining with the IP-10 antibody at all levels of the epidermis, with accentuation in areas of blister formation. There was more intense staining of keratinocytes with the IP-10 antibody in cases with accumulations of HLA-DR positive lymphocytes in the dermis. We believe that these findings are consistent with the hypothesis that FDE represent cell-mediated immunologic responses to a variety of antigens, and further, that the histologic alterations can be explained, at least in part, by a cytokine-mediated process.

Detection of the interferon-gamma-induced protein 10 in psoriasiform dermatitis of acquired immunodeficiency syndrome.

Interferon-gamma-induced protein 10 is a 10-kd protein produced by human keratinocytes following an exposure to interferon gamma. Keratinocytes within psoriatic plaques and within delayed-type hypersensitivity reactions have been shown to stain strongly with an affinity-purified rabbit antibody prepared against interferon-gamma-induced protein 10, suggesting a possible role for interferon gamma in the production of the lesions. A psoriasiform eruption has been seen in patients with acquired immunodeficiency syndrome (AIDS). Its severity appears to correlate with the degree of immunodeficiency in the early stages of AIDS. We stained 10 lesions of psoriasiform dermatitis of AIDS with the anti-interferon-gamma-induced protein 10 antibody using immunoperoxidase techniques. As controls, we studied 10 lesions of non-AIDS psoriasis, six lesions of seborrheic dermatitis with psoriasiform hyperplasia, one lesion of lichen simplex chronicus, and four biopsy specimens of normal skin from patients with AIDS. In addition, normal skin specimens taken from patients with AIDS and human immunodeficiency virus-negative patients at time of autopsy were examined. An identical, strong and diffuse staining pattern was seen in all cases of psoriasiform dermatitis of AIDS, non-AIDS psoriasis, seborrheic dermatitis, and lichen simplex chronicus. The specimens of normal skin showed only weak basal layer staining with anti-interferon-gamma-induced protein 10. Thus, the presence of interferon-gamma-induced protein 10 in keratinocytes was associated with psoriasiform hyperplasia and could be detected in both AIDS-associated and classic psoriasis.

An unusual cutaneous manifestation of Crohn's disease.

Crohn's disease is a multisystem disease that involves the skin in approximately 20% of afflicted individuals. Most often, it is characterized by an erythema nodosum-like reaction or by a fistulous tract in skin adjacent to mucosal membranes. We recently saw a patient who presented with crusted malar plaques and a long-standing history of Crohn's disease. The skin lesions relapsed and recurred in concert with exacerbations of the gastrointestinal disorder. On biopsy, the sections showed a diffuse neutrophilic inflammatory infiltrate. There was no evidence of a granulomatous infiltrate on step sections through the block. We believe this to be a previously unrecognized pattern of Crohn's disease involving the skin.

Neurofibromas and neurotized melanocytic nevi are immunohistochemically distinct neoplasms.

Neurofibromas are often clinically, as well as histologically, indistinguishable from completely neurotized melanocytic nevi. We tested the hypothesis that immunologic markers would differentiate the perineural fibroblasts and Schwann cells of neurofibromas from the neurotized cells of melanocytic origin. We examined eight partially neurotized acquired melanocytic nevi, three partially neurotized congenital melanocytic nevi, and five neurofibromas, with antibodies directed against S-100 protein, Leu-7(HNK-1), glial fibrillary acid protein (GFAP), and myelin-basic protein (MBP). A histologic diagnosis of neurofibroma was based on identification of a dermal proliferation of spindle-shaped cells with wavy nuclei, in a background of loose reticulated collagen. Neurotized nevi were diagnosed upon recognition of scattered nests of type A or B nevus cells, surrounded by basement membrane, present in the papillary dermis of lesions otherwise indistinguishable from neurofibromas. The congenital nevi were all large melanocytic nevi known to be present at birth. S-100 stained the majority of neoplastic cells in all neurofibromas, neurotized acquired nevi, and neurotized congenital nevi. Neurofibromas showed focal staining for Leu-7, GFAP, and MBP. In contrast, neurotized acquired and congenital nevi failed to express these markers. We believe that Leu-7, GFAP, and MBP may be helpful in differentiating neurofibromas from completely neurotized melanocytic nevi. The differences in the immunohistochemical profiles of neurofibromas and neurotized nevi support the concept that these neoplasms are histogenically distinct, despite their similar histologic appearance.

Primary lymphoma of bone. A B-cell neoplasm with a high frequency of multilobated cells.

Primary lymphoma of bone is an uncommon neoplasm that can be difficult to diagnose and subclassify. Only in a few cases has the immunophenotype been determined with monoclonal antibodies. We evaluated the histological features and immunophenotype of 12 cases of primary lymphoma of bone. The patients ranged in age from 16 to 80 years (mean, 41 years) with a male:female ratio of 1:1. The sites involved included femur (three cases), humerus (two cases), tibia (three cases), pelvis (two cases), ulna (one case), and scapula (one case). All cases were diffuse large-cell lymphomas: nine large-cleaved (eight with multilobated cells), two large-cell not otherwise specified, and one immunoblastic. Sclerosis was noted in six cases. Immunohistochemical studies on frozen-tissue sections demonstrated staining with the following antibodies: 11 of 11 with CD45, 12 of 12 with CD20, eight of 12 with monotypic immunoglobulin (six IgG, two IgM, seven kappa, one lambda). Tumor cells were negative for T-cell markers in each case. Ten patients are alive and well 0.5-4.5 years (median, 1.5 years) following treatment with radiation or chemotherapy. Two patients had recurrence at another site 0.75 years and 4 years after the initial diagnosis, respectively. Primary bone lymphoma is a B-lineage large-cell lymphoma with an unusually high incidence of large-cleaved and multilobated cells. The frequency of IgG heavy chain expression suggests a post-germinal center stage of differentiation. Frozen section immunohistologic studies are useful in the diagnosis of this tumor. Aggressive therapy has resulted in a favorable outcome in most cases.

Immunohistochemical demonstration of factor XIIIa expression in neurofibromas. A practical means of differentiating these tumors from neurotized melanocytic nevi and schwannomas.

Neurofibromas, schwannomas, and neurotized melanocytic nevi may closely resemble one another at the light microscopic level. We studied 10 neurofibromas, 10 schwannomas, and 10 partially neurotized melanocytic nevi immunohistochemically using an antibody directed against factor XIIIa to determine if this antibody might provide a useful method of differentiating these lesions. The cases were also stained with S100 protein. All of the neurofibromas stained intensely for factor XIIIa. The proportion of cells staining within the tumors varied from 30% to 70%. In contrast, none of the schwannomas and neurotized nevi studied demonstrated staining of tumor cells with this antibody. S100 protein was expressed by 100% of neurofibromas, schwannomas, and melanocytic nevi. Our findings suggest that factor XIIIa may provide a reliable and practical means of differentiating cutaneous neurofibromas from neurotized nevi and cutaneous schwannomas. Distinguishing between these different tumor types may be important in some clinical situations, particularly with respect to rendering a diagnosis of von Recklinghausen's neurofibromatosis. The differences in the immunohistochemical profiles of neurofibromas and neurotized nevi support the concept that these tumors are histogenetically distinct, despite their similar histologic appearances.

Cytokeratin expression in epithelioid vascular neoplasms.

Seven epithelioid and eight non-epithelioid vascular tumors were studied by the avidin-biotin-peroxidase method for the presence of endothelial- and epithelial-associated markers, using Ulex europaeus agglutinin-1 (UEA-1) lectin, and antibodies directed against factor VIII-related antigen, (FVIII-RA), vimentin, keratin, carcinoembryonic antigen, and epithelial membrane antigen. The cases included four epithelioid hemangiomas, two epithelioid hemangioendotheliomas (EHE), one epithelioid angiosarcoma (EAS), four common non-epithelioid capillary hemangiomas, and four non-epithelioid angiosarcomas. Staining for FVIII-RA, UEA-1, and vimentin were observed in all cases. The EAS showed staining for keratin in formalin-fixed, paraffin-embedded sections and in frozen sections. Staining for keratin was also observed in frozen sections of one EHE. Both keratin-positive vascular tumors were confirmed with electron microscopy. Carcinoembryonic antigen and epithelial membrane antigen stains were negative in all cases. Our results show that the epithelioid vascular tumors EHE and EAS, in addition to staining for the endothelial markers and vimentin, may also express the epithelial marker keratin. This is important since these tumors may closely resemble carcinomas by routine light microscopy. This study further underscores the importance of using a broad panel of immunohistochemical markers in the diagnostic workup of soft-tissue neoplasms.

Changes seen in lymph nodes draining the sites of large joint prostheses.

We report the histological findings seen in the lymph nodes draining the sites of large joint prostheses. Two patients underwent multiple prosthetic joint replacements. In one patient, the regional lymph nodes were enlarged during the revision of a total hip prosthesis, and a representative lymph node was resected. The other patient had undergone a pelvic lymph node dissection as part of a staging procedure for prostatic carcinoma. By light microscopy, the lymph nodes from both patients showed markedly dilated nodal sinuses filled with macrophages containing abundant eosinophilic, PAS-positive, granular material. Polarization microscopy revealed needle-like particles within the cytoplasm of the macrophages. We believe that the histological appearance of the lymph nodes represents a florid foreign body reaction to fragments of polyester or polyethylene derived from the articulating surfaces of the joint prostheses and transported to the regional lymph nodes via the lymphatic circulation. Sinus histiocytosis seen in the lymph nodes draining the sites of joint prostheses may resemble, and must be distinguished from, other conditions invoking a sinus pattern of lymphadenopathy, as well from benign and malignant diseases that involve the lymph nodes in a pattern mimicking sinus histiocytosis.

Glial fibrillary acidic protein and keratin expression by benign and malignant nerve sheath tumors.

Formalin-fixed, paraffin-embedded sections of 59 ultrastructurally confirmed nerve sheath tumors (NSTs) that included 27 benign schwannomas, five neurofibromas, and 27 malignant schwannomas were studied by the avidin-biotin-peroxidase complex method using antibodies directed against glial fibrillary acidic protein (GFAP), keratin, S-100 protein, vimentin, and desmin. GFAP was expressed by 33% of the benign schwannomas, 40% of the neurofibromas, and 7% of the malignant schwannomas. Keratin was expressed by 7% of the benign schwannomas and 4% of the malignant schwannomas. S-100 protein was expressed by 100% of the benign NSTs and by 40% of the malignant schwannomas. Vimentin was observed in 100% of the benign NSTs and in 85% of the malignant schwannomas. None of the cases stained for desmin. GFAP and cytokeratin expression could not be predicted on the basis of tumor light microscopy or ultrastructure. These findings are of practical importance in routine surgical pathology, particularly with respect to the differential diagnosis of gliomas located in the central nervous system and in immunohistochemical studies of peripherally located, poorly differentiated neoplasms.

Xanthomatous infiltrate of the face.

We report 2 cases which shared an unusual histopathologic pattern of a xanthomatous infiltrate occurring on the nose. Both patients were women in their fifth decade. Each presented to the dermatology clinic with multiple soft, flesh-colored papules, up to 1 cm, in diameter on the lateral aspects of the nose. The lesions had been present for several years. Both patients were otherwise completely well, and asymptomatic. In one case, focal telangiectasia and central umbilication was noted, and the clinical differential diagnoses included basal cell carcinomas and appendageal tumors. In each case, a biopsy was performed. The lesions appeared histologically quite similar. The epidermis was unremarkable. Within the dermis, there was a mid-reticular dermal infiltrate of macrophages with unilocular and multilocular fat laden cytoplasm, and scalloped nuclei. Only a scant inflammatory infiltrate of lymphocytes and histiocytes was present. Minimal dermal fibrosis was also present. We believe that xanthomatous infiltrate of the face is a distinct clinical entity which presents as multiple flesh-colored papules on the nose, which have a characteristic histologic appearance of abundant lipid-laden macrophages within the dermis.

Cardiac assistance with electrically stimulated skeletal muscle.

This study examined the ability of a skeletal muscle-powered assist ventricle (SMV) to augment cardiac output in ten dogs with pharmacologically induced heart failure under acute conditions. An SMV was surgically constructed in each dog by wrapping the untrained rectus abdominis muscle around a compressible pouch that was inserted into a left ventricular apex-to-aortic vascular conduit. The multiple motor nerves to the rectus muscle were then stimulated during ventricular diastole at a rate which equalled a ratio of 1:2, 1:3, or 1:4 with the natural ventricular beat. There was an increased cardiac output during SMV assistance compared with preassistance values in all ten dogs at each stimulation ratio with a mean increase of 46 +/- 4 per cent with a ratio of 1:2, 25 +/- 4 per cent with a ratio of 1:3, and 31 +/- 7 per cent with a ratio of 1:4 (p less than 0.01 for all values). The diastolic blood pressure and mean blood pressure were both increased (p less than 0.01 and p less than 0.05, respectively) during SMV stimulation at ratios of 1:2 and 1:3, but not 1:4. We have shown that untrained rectus abdominis muscle, when used as the power supply for a SMV in an apico-aortic conduit, can temporarily augment cardiac output in dogs with pharmacologically induced heart failure.

The effect of pregnant mare serum gonadotropin on mouse oocytes as monitored at metaphase II.

Ovulated oocytes were collected from random-bred, 7-12 week old ICR mice injected with 0, 3, or 6 i.u. pregnant mare serum gonadotropin (PMSG). Analyses of 872 metaphase figures from 87 females did not show a significant increase in chromosomal imbalance with PMSG treatment. A tendency toward ovum fragmentation was noted with an increase in PMSG dose.