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PubMed1982

Spindle microtubules and their mechanical associations after micromanipulation in anaphase.

Micromanipulation of living grasshopper spermatocytes in anaphase has been combined with electron microscopy to reveal otherwise obscure features of spindle organization. A chromosome is pushed laterally outside the spindle and stretched, and the cell is fixed with a novel, agar-treated glutaraldehyde solution. Two- and three-dimensional reconstructions from serial sections of seven cells show that kinetochore microtubules of the manipulated chromosome are shifted outside the confusing thicket of spindle microtubules and mechanical associations among microtubules are revealed by bent or shifted microtubules. These are the chief results: (a) The disposition of microtubules invariably is consistent with a skeletal role for spindle microtubules. (b) The kinetochore microtubule bundle is composed of short and long microtubules, with weak but recognizable mechanical associations among them. Some kinetochore microtubules are more tightly linked to one other microtubule within the bundle. (c) Microtubules of the kinetochore microtubule bundle are firmly connected to other spindle microtubules only near the pole, although some nonkinetochore microtubules of uncertain significance enter the bundle nearer to the kinetochore. (d) The kinetochore microtubules of adjacent chromosomes are mechanically linked, which provides an explanation for interdependent chromosome movement in "hinge anaphases." In the region of the spindle open to analysis after chromosome micromanipulation, microtubules may be linked mechanically by embedment in a gel, rather than by dynein or other specific, cross-bridging molecules.

Anaphase↗

PubMed1983

Intranuclear membranes and the formation of the first meiotic spindle in Xenos peckii (Acroschismus wheeleri) oocytes.

The ultrastructure of spindle formation during the first meiotic division in oocytes of the Strepsipteran insect Xenos peckii Kirby (Acroschismus wheeleri Pierce) was examined in serial thick (0.25-micron) and thin sections. During late prophase the nuclear envelope became extremely convoluted and fenestrated. At this time vesicular and tubular membrane elements permeated the nucleoplasm and formed a thin fusiform sheath, 5-7 micron in length, around each of the randomly oriented and condensing tetrads. These membrane elements appeared to arise from the nuclear envelope and/or in association with annulate lamellae in the nuclear region. All of the individual tetrads and their associated fusiform sheaths became aligned within the nucleus subsequent to the breakdown of the nuclear envelope. Microtubules (MTs) were found associated with membranes of the meiotic apparatus only after the nuclear envelope had broken down. Kinetochores, with associated MTs, were first recognizable as electron-opaque patches on the chromosomes at this time. The fully formed metaphase arrested Xenos oocyte meiotic apparatus contained an abundance of membranes and had diffuse poles that lacked distinct polar MT organizing centers. From these observations we conclude that the apparent individual chromosomal spindles--seen in the light microscope to form around each Xenos tetrad during "intranuclear prometaphase" (Hughes-Schrader, S., 1924, J. Morphol. 39:157-197)--actually form during late prophase, lack MTs, and are therefore not complete miniature bipolar spindles, as had been commonly assumed. Thus, the unique mode of spindle formation in Xenos oocytes cannot be used to support the hypothesis that chromosomes (kinetochores) induce the polymerization of their associated MTs. Our observation that MTs appeared in association with and parallel to tubular membrane components of the Xenos meiotic apparatus after these membranes became oriented with respect to the tetrads, is consistent with the notion that membranes associated with the spindle determine the orientation of spindle MTs and also play a part in regulating their formation.

Animals↗

PubMed1984

Rapid rate of tubulin dissociation from microtubules in the mitotic spindle in vivo measured by blocking polymerization with colchicine.

At metaphase, the amount of tubulin assembled into spindle microtubules is relatively constant; the rate of tubulin association equals the rate of dissociation. To measure the intrinsic rate of dissociation, we microinjected high concentrations of colchicine, or its derivative colcemid, into sea urchin embryos at metaphase to bind the free tubulin, thereby rapidly blocking polymerization. The rate of microtubule disassembly was measured from a calibrated video signal by the change in birefringent retardation (BR). After an initial delay after injection of colchicine or colcemid at final intracellular concentrations of 0.1-3.0 mM, BR decreased rapidly and simultaneously throughout the central spindle and aster. Measured BR in the central half-spindle decreased exponentially to 10% of its initial value within a characteristic period of approximately 20 s; the rate constant, k = 0.11 +/- 0.023 s-1, and the corresponding half-time, t 1/2, of BR decay was approximately 6.5 +/- 1.1 s in this concentration range. Below 0.1 mM colchicine or colcemid, the rate at which BR decreased was concentration dependent. Electron micrographs showed that the rapid decrease in BR corresponded to the disappearance of nonkinetochore microtubules; kinetochore fiber microtubules were differentially stable. As a control, lumicolchicine, which does not bind to tubulin with high affinity, was shown to have no effect on spindle BR at intracellular concentrations of 0.5 mM. If colchicine and colcemid block only polymerization, then the initial rate of tubulin dissociation from nonkinetochore spindle microtubules is in the range of 180-992 dimers per second. This range of rates is based on k = 11% of the initial polymer per second and an estimate from electron micrographs that the average length of a half-spindle microtubule is 1-5.5 micron. Much slower rates of tubulin association are predicted from the characteristics of end-dependent microtubule assembly measured previously in vitro when the association rate constant is corrected for the lower rate of tubulin diffusion in the embryo cytoplasm. Various possibilities for this discrepancy are discussed.

Animals↗

PubMed1988

Effect of 1,2-propanediol and dimethylsulphoxide on the meiotic spindle of the mouse oocyte.

At ovulation, the mouse oocyte is arrested at metaphase of the second meiotic division. Since microtubules are thermo-and chemosensitive structures, the effects of 1.5 M dimethylsulphoxide and 1.5 M 1,2-propanediol were studied at room temperature on the morphology of the meiotic spindle. Oocytes incubated at 37 degrees C or at room temperature served to estimate the effect of temperature in the experiment. The meiotic spindle was visualized by immunogold-silver staining of microtubules. In the control group at 37 degrees C, 88% of oocytes had normal spindles. After incubation at room temperature for the same time, 89% of oocytes showed abnormal spindles. In the oocytes exposed to dimethyl-sulphoxide or 1,2-propanediol at room temperature a protective effect on spindle morphology could be recognized. Subsequent incubation at 37 degrees C resulted in partial restoration of the observed abnormalities after cooling to room temperature and after exposure to dimethylsulphoxide. Incubation at 37 degrees C after exposure to 1,2-propanediol at room temperature induced spindle absence in the majority of oocytes. Although this latter condition allowed fertilization without increased incidence of ploidy abnormalities, a role for 1,2-propanediol as an activating agent is hypothesized.

Animals↗

PubMed1987

Sleep spindle activity changes in patients with affective disorders.

Various polysomnographic sleep patterns are associated with affective disorders, but very little is known about sleep spindle characteristics in adult depression. In primary endogenous depressive male patients (unipolar, UP, and bipolar, BP) with comparable depression scores and in normal control subjects recorded during 3 consecutive nights, no night effect was observed on the sleep variables investigated except for REM latencies of stages 1 and 2. Stage 2 duration and variables related to sleep spindle characteristics (the number and the density of spindles of 1/2 s; the number and the density of full spindles of stage 2 over the 3 nights) were significantly lower in depressed patients than in control subjects, the mean number of spindles being lower in UP than in BP patients. Sleep spindle measures were clearly negatively correlated with age in the overall group (i.e., depressed plus control subjects). They were also negatively correlated with the REM latencies of stages 1 and 2 in BP depressed patients, whereas this relation was not observed in UP patients.

Adult↗

PubMed1999

Postoperative/posttraumatic spindle cell nodule of the skin: the dermal analogue of nodular fasciitis.

Spindle cell proliferations of the skin are diverse, both morphologically and mechanistically. The authors have encountered four examples of a distinctive reactive/reparative cutaneous spindle cell lesion that shows homology with ones seen in the genitourinary tract and oral cavity and that is known as "postoperative/posttraumatic spindle cell nodule" (PSCN). These occurred in the skin of the face and scalp (2 cases), arm (1 case), and vulvar skin (one case), and were clearly related historically to prior episodes of trauma. The proliferations were characterized by variably-apposed and cytologically-bland spindle cells with numerous mitotic figures, set in a highly vascular stroma containing extravasated erythrocytes and inflammatory cells. All lesions were immunoreactive for vimentin, actin, and desmin, with no labeling for keratin. Postoperative/posttraumatic spindle cell nodule of the skin is a significant pseudoneoplastic lesion that is related (and perhaps identical pathogenetically) to nodular fasciitis; as such, it may be mistaken for a sarcoma or a spindle cell carcinoma. Careful attention to clinicopathologic and histologic details should result in its accurate recognition.

Adult↗

PubMed2000

Cutaneous spindle-cell B-cell lymphoma: a morphologic variant of cutaneous large B-cell lymphoma.

The morphologic spectrum of large B-cell lymphoma is broad. Several unusual variants have been described such as lymphoma with myxoid stroma, sclerosing B-cell lymphoma, signet ring-cell lymphoma, and multilobated B-cell lymphoma among others. We report on five cases of cutaneous large B-cell lymphoma in which the neoplastic cells were spindle-shaped. In two cases, the clinical features fulfilled those of a primary cutaneous lymphoma; in the three other cases, the lymphoma most likely arose primarily in the skin, but incomplete clinical workups precluded definite categorization. The patients ranged in age from 30 to 89 years and presented with solitary lesions on the trunk or head. Histopathologic examination revealed nodular or dense diffuse infiltrates involving the entire dermis as well as the subcutaneous fat in some cases. Thickened collagen bundles between the spindled cells were present in one case. Cytomorphologic analysis showed the presence of round or oval medium-sized and large-sized lymphocytes with features of centrocytes and centroblasts in some foci, with others dominated by cells with spindle-shaped, elongated, twisted nuclei with dispersed chromatin and scant cytoplasm. Immunohistologic analysis revealed that both round or oval and spindled cells were positive for CD20 in all cases; in all cases tested, these cells were also positive for MIB-1 and were negative for CD3, CD5, CD43, CD45RO, CD21, CD30, CD68, S-100, HMB-45, actin, smooth-muscle actin, and cytokeratin. Bcl-2 was expressed in one of three cases tested. Analysis of the rearrangement of the J(H) gene by polymerase chain reaction performed in one case showed a monoclonal pattern. Spindle-cell large B-cell lymphoma represents a distinctive rare subtype of the cutaneous large B-cell lymphoma and can arise primarily in the skin in some cases. Recognition of this variant is necessary to avoid misdiagnosis of other cutaneous malignant spindle-cell tumors.

Adult↗

PubMed2001

Fibrous spindle cell lipoma: report of a new variant.

Spindle cell lipoma is a benign tumor characterized by mature fatty tissue alternating with short fascicles of small spindle cells in a stroma that varies from fibrous to myxoid. The variable proportion of these elements among different examples of the neoplasm confers to spindle cell lipoma a variable microscopic appearance that can make the diagnosis difficult. Furthermore, in some instances, spindle cell lipoma may resemble liposarcoma, hemangiopericytoma, neurilemmoma, and other neoplasms representing a histopathologic pitfall. We report on two cases of spindle cell lipoma with abundant fibrous stroma reminiscence of fibroma and fibrolipoma. The name fibrous spindle lipoma is proposed for this tumor.

Adipocytes↗

PubMed1987

Spindle-cell carcinoma of the aerodigestive tract. An immunohistochemical analysis of 21 cases.

Immunohistochemical analysis of 21 prototypic mucosal spindle-cell carcinomas of the aerodigestive tract was performed at the Armed Forces Institute of Pathology (AFIP) to establish the usefulness of selected immunohistochemical markers in distinguishing spindle-cell carcinoma from other mucosal spindle-cell neoplasms. Immunoreactive keratin could be demonstrated in only 13/21 (62%) of cases. Coexpression of keratin and vimentin was demonstrated in 10/17 (59%) of the tumors evaluated for both of these intermediate filaments. All spindle-cell carcinomas lacked S100 protein, which is an immunoreactivity we would expect to find in spindle-cell malignant melanoma, one of the principal considerations in a differential diagnosis. Both alpha-1-antitrypsin (AAT) and alpha-1-antichymotrypsin (ACT) were demonstrated in the tumor cells in all cases. However, albumin had a similar distribution in the tumors, which suggested that passive uptake was a serious confusing factor. The results of this study indicate that AAT and ACT are unreliable markers for distinguishing spindle-cell carcinomas from malignant fibrous histiocytomas.

Aged↗

PubMed1994

Spindle cell pseudotumors in the lungs due to Mycobacterium tuberculosis in a transplant patient.

A rare spindle cell pseudotumor in the skin, lymph nodes, and bone marrow has been previously reported in immunosuppressed transplant patients and patients with acquired immunodeficiency syndrome. All reported cases were caused by Mycobacterium avium-intracellulare or other nontuberculous mycobacteria. We are reporting spindle cell pseudotumors in the lungs caused by Mycobacterium tuberculosis. The patient had insulin-dependent diabetes mellitus and was status post cadaveric renal and pancreatic transplants. His hospital course was complicated by pulmonary tuberculosis due to M. tuberculosis. At autopsy, the lungs showed numerous bilateral gray nodules ranging from 0.2 to 2.5 cm. Microscopic examination uncovered a cellular proliferation composed of spindle cells arranged in fascicles. There were no granulomata. An acid-fast stain showed numerous acid-fast bacilli within the spindle cells. To our knowledge, this is the first case of spindle cell pseudotumor caused by M. tuberculosis of the lungs. Awareness of this unusual manifestation of mycobacterial infection in immunosuppressed patients underscores the need for acid-fast staining of biopsies with spindle cell proliferation even in the absence of overt granulomatous lesions in order to prevent misdiagnosis.

Adult↗

PubMed1999

Hyalinizing spindle cell tumor with giant rosettes: a report of three cases with ultrastructural analysis.

We report the light microscopic, ultrastructural appearance and immunohistochemical staining profile of three distinctive soft-tissue tumors recently designated hyalinizing spindle cell tumor with giant rosettes. The tumors occurred in two men, 41 and 54 years old, and one woman, 62 years old. Two tumors arose in the lower extremities and one in the upper arm. Two tumors were resected and measured 3 and 13.2 cm in greatest diameter; a biopsy only was done of the third tumor. Grossly, the tumors had a tan, pink, or white cut surface. The largest tumor exhibited central cystic change. Microscopically, they all displayed similar features and were composed of fibromyxoid regions, with areas of hyalinization in two tumors and focal ossification in one tumor. Scattered throughout each of the tumors were rosette-like structures in which neoplastic cells were arranged around a central collagenous core. Ultrastructurally, the neoplastic cells demonstrated the features of fibroblasts. In all tumors, there was abundant extracellular collagen fibers and in one there were large aggregates of amorphous extracellular external lamina-like material. The center of the rosette-like structures was composed of banded collagen fibers and the cells at the periphery of the rosettes had ultrastructural features similar to the neoplastic spindle cells located elsewhere in the tumor. Immunohistochemically, the tumor cells stained for vimentin. There was focal staining of the widely distributed spindle cells and cells that formed the rosettes for Leu-7, S-100 protein, and CD34. In one tumor, there was faint diffuse staining of the spindle cells for neuron-specific enolase. One tumor (with the amorphous extracellular material) stained for type IV collagen. There was no staining for desmin, muscle actin, smooth muscle actin, keratin, or epithelial membrane antigen. These results demonstrate that hyalinizing spindle cell tumor with giant rosettes is composed of fibroblasts. We did not demonstrate any ultrastructural or immunohistochemical differences between the spindle cells that comprised the majority of the mass and those that surrounded the rosette-like structures. There was no ultrastructural evidence of neural differentiation to explain the focal S-100 protein and Leu-7 staining of the tumor cells.

Adult↗

PubMed2001

Low-grade (fibromatosis-like) spindle cell carcinoma of the breast.

Spindle cell carcinoma of the breast, a variant of metaplastic carcinoma, includes a wide spectrum of lesions with histomorphologic and nuclear features ranging from overtly malignant to mildly atypical. Spindle cell carcinomas with mildly atypical features may resemble fasciitis, fibromatosis, or myofibroblastic tumors and therefore are often misinterpreted as such. A recent study has suggested that spindle cell carcinomas with a dominant fibromatosis-like phenotype, unlike spindle cell carcinomas in general, have no propensity for distant metastasis and should be termed "tumors" rather than "carcinomas." To investigate the question of fibromatosis-like spindle cell breast carcinoma (FLSpCCs) metastatic potential, we studied cases of FLSpCC seen at the University of Texas M.D. Anderson Cancer Center between 1987 and 2000. Clinical, pathologic, and immunophenotypic features were reviewed, with emphasis on biologic behavior and predictors of clinical outcome. Our series included 24 women who ranged in age from 55 to 85 years (mean 66 years). Tumor size ranged from 1.0 to 5 cm (mean 2.8 cm). Most tumors were grossly well defined but had microscopic infiltrative borders. Tumors showed a dominant fibromatosis-like or myofibroblastic-like growth pattern with prominent collagenization. Inflammatory infiltrate was noted in the majority of tumors. Cytokeratin-positive cells were seen in all cases and usually appeared as cords or sheets of polygonal cells; isolated cytokeratin-positive cells were rare. In most tumors immunoreactivity for smooth muscle actin (SMA) was confined to the cytokeratin-negative cells. In five cases intense co-expression of cytokeratin and SMA was noted. None of the tumors showed immunoreactivity for smooth muscle heavy chain myosin, estrogen receptors, progesterone receptors, or HER-2/neu. Ki-67 expression was noted in fewer than 5% of tumor cells. Treatment consisted of local excision (seven cases) or modified radical mastectomy (13 cases). Treatment was unknown in four cases. In patients who underwent axillary nodal dissection, no lymph node metastases were found. Two of the six patients who underwent local excision developed local recurrence. Two patients who underwent modified radical mastectomy developed lung metastases within 2 years after the initial diagnosis. The metastatic tumors were histologically similar to the primary tumors. Our findings indicate that FLSpCCs have the potential for local recurrence and distant metastasis and should be treated accordingly. Because FLSpCCs may be underdiagnosed as benign, the use of immunohistochemical studies, especially for cytokeratins and SMA, is essential in the evaluation of any spindle cell proliferations of the breast.

Actins↗

PubMed1995

Solitary and generalized variants of spindle cell xanthogranuloma (progressive nodular histiocytosis).

Twelve cases of solitary spindle cell xanthogranuloma, seven of which had originally been misdiagnosed as dermatofibroma/benign fibrous histiocytoma, were clinicopathologically compared with four cases of progressive nodular histiocytosis, a rare generalized non-X histiocytic disorder. Clinically, a single brown-yellowish papule or nodule is characteristic of solitary spindle cell xanthogranuloma, multiple generalized lesions of progressive nodular histiocytosis. Solitary spindle cell xanthogranuloma occurs with decreasing frequency on the head, neck, upper trunk, or occasionally the extremities of young adults (aged 20-40 years), progressive nodular histiocytosis mostly on the trunk of older patients (aged 40-60 years), both without sex predilection. Histologically, both entities are characterized by predominance (> 90%) of spindle-shaped histiocytes arranged in a storiform pattern. Other mononuclear (vacuolated, xanthomatized, scalloped, oncocytic) and multinucleate (Touton) histiocytes are also regularly seen. Immunohistochemically, both entities exhibit a macrophage/dendritic cell lineage positive for KP1/Ki-M1p (CD68), HAM 56 and factor XIIIa as well as for smooth muscle specific actin and HHF35. Ultrastructurally, dense, regularly laminated, myeloid or pleomorphic cytoplasmic inclusions may be found, but no Birbeck granules are present. This study documents that both solitary spindle cell xanthogranuloma and progressive nodular histiocytosis are distinct entities within the spectrum of a xanthogranulomatous reaction characterized by predominance of spindle-shaped histiocytes.

Adolescent↗

PubMed2005

A population-based model of the nonlinear dynamics of the thalamocortical feedback network displays intrinsic oscillations in the spindling (7-14 Hz) range.

The thalamocortical network is modelled using the Wilson-Cowan equations for neuronal population activity. We show that this population model with biologically derived parameters possesses intrinsic nonlinear oscillatory dynamics, and that the frequency of oscillation lies within the spindle range. Spindle oscillations are an early sleep oscillation characterized by high-frequency bursts of action potentials followed by a period of quiescence, at a frequency of 7-14 Hz. Spindles are generally regarded as being generated by intrathalamic circuitry, as decorticated thalamic slices and the isolated thalamic reticular nucleus exhibit spindles. However, the role of cortical feedback has been shown to regulate and synchronize the oscillation. Previous modelling studies have mainly used conductance-based models and hence the mechanism relied upon the inclusion of ionic currents, particularly the T-type calcium current. Here we demonstrate that spindle-frequency oscillatory activity can also arise from the nonlinear dynamics of the thalamocortical circuit, and we use bifurcation analysis to examine the robustness of this oscillation in terms of the functional range of the parameters used in the model. The results suggest that the thalamocortical circuit has intrinsic nonlinear population dynamics which are capable of providing robust support for oscillatory activity within the frequency range of spindle oscillations.

Animals↗

PubMed1976

Spindle cell lipoma.

A clinical, light- and electronmicroscopic study of 14 patients with spindle cell lipoma is presented. Spindle cell lipoma is considered to be a distinctive lipomatous tumour histologically characterized by a mixture of fat cells and fibroblast-like spindle cells, ultrastructurally similar to fibroblasts, in a matrix with varying amounts of collagen and mucosubstances. The tumours showed a predominance for elderly men and all but one were situated in the posterior neck, shoulder region or upper back. The tumours varied between 1 and 9 cm, with a median value of 5 cm, in the widest diameter and were entirely or almost entirely situated in the subcutaneous tissue. A follow-up study of 11 patients, observed for 1-25 years, confirmed that the clinical course is benign. The differential diagnosis is discussed and it is emphasized that spindle cell lipoma is easily misinterpreted as sarcoma. Three tumours showed a pronounced nuclear polymorphism without mitotic activity, thought to be regressive in nature. The cellular change in these three tumours are presumed to be analogous with those in so called ancient neurilemmoma and therefore the name ancient spindle cell lipoma is proposed for the polymorphic spindle cell lipomas.

Adult↗

PubMed1989

Spindle cell carcinoma of the larynx.

The clinicopathological features of 14 laryngeal neoplasms consisting of spindle-shaped cells are presented. Light microscopy showed a variety of morphological patterns from that of pleomorphic sarcoma and fibrosarcoma to more loose vascular patterns. Immunohistochemistry revealed that the spindle-shaped cells had a positive keratin immunoreactivity in 8 of 14 cases, and also that some cases had a dual expression of keratin and vimentin filaments. Electron microscopy showed that spindle-shaped cells had epithelial ultrastructures. The results support the hypothesis that the spindle cell carcinomas are true carcinomas with mesenchymal metaplasia and that the spindle-shaped cells are part of the neoplasm and not benign, reactive fibroblasts. These lesions occurred mainly on the true vocal cords in elderly patients. The neoplasms were nearly all polypoid, and many also ulcerated. There is no significant difference in clinical behaviour between laryngeal spindle cell carcinomas and ordinary squamous cell carcinomas of the larynx, and the same treatment policy is therefore advocated. Being polypoid and therefore able to be surgically removed with relative ease, they may even present a more favourable clinical course.

Adult↗

PubMed2001

Spindle cell conversion by Kaposi's sarcoma-associated herpesvirus: formation of colonies and plaques with mixed lytic and latent gene expression in infected primary dermal microvascular endothelial cell cultures.

Angiogenic Kaposi's sarcoma (KS) skin lesions found in both AIDS and non-AIDS patients are universally associated with infection by the presumed causative agent, known as KS-associated herpesvirus (KSHV) or human herpesvirus 8. KSHV genomes expressing latent state virus-encoded mRNAs and the LANA1 (latent nuclear antigen 1) protein are consistently present in spindle-like tumor cells that are thought to be of endothelial cell origin. Although the KSHV lytic cycle can be induced in rare latently infected primary effusion lymphoma (PEL) cell lines, the ability to transmit or assay infectious KSHV has so far eluded investigators. Here, we demonstrate that infection with supernatant virions derived from three different tetradecanoyl phorbol acetate-induced PEL cell lines can induce cultured primary human dermal microvascular endothelial cells (DMVEC) to form colonies of proliferating latently infected spindle-shaped cells, all of which express the KSHV-encoded LANA1 protein. Although their initial infectivity varied widely (JSC1 > > BC3 > BCP1), virions from all three cell lines produced distinctive spindle cell colonies and plaques without affecting the contact-inhibited cobblestone-like phenotype of adjacent uninfected DMVEC. Each infected culture could also be expanded into a completely spindloid persistently infected culture displaying aggregated swirls of spindle cells resembling those in KS lesions. Formation of new colonies and plaques was inhibited in the presence of phosphonoacetic acid or gangciclovir, but these antiherpesvirus agents had little effect on the propagation of already latently infected spindloid cultures. In persistently infected secondary cultures, patches of up to 10% of the spindloid cells constitutively expressed several early viral lytic cycle proteins, and 1 to 2% of the cells also formed typical herpesvirus DNA replication compartments, displayed cytopathic rounding effects, and expressed late viral antigens. We conclude that de novo KSHV infection induces a spindle cell conversion phenotype in primary DMVEC cultures that is directly associated with latent state expression of the LANA1 protein. However, these cultures also spontaneously reactivate to produce an unusual combination of both latent and productive but slow lytic cycle infection. The formation of spindle cell colonies and plaques in DMVEC cultures provides for the first time a quantitative assay for directly measuring the infectivity of KSHV virion preparations.

Antigens, Viral↗

PubMed2006

Spindle cell carcinoma of head and neck: an immunohistochemical and molecular approach to its pathogenesis.

BACKGROUND: Spindle cell carcinoma (SpCC) is a rare microscopic type of cancer of the mouth and oropharynx. Although SpCC is thought to arise from squamous cell carcinoma (SCC), it carries a worse prognosis. AIM: To find out the difference in immunohistochemical expression of cytokeratin, vimentin and smooth-muscle actin, and mutational alterations in the K-ras oncogene between the two tumours, in an attempt to characterise SpCC. METHODS: Immunohistochemical analysis was performed by standard avidin-biotin complex method in 35 cases each of SpCCs and SCCs. DNA extracted from paraffin wax-embedded tumours was used for PCR followed by single-strand conformation polymorphism for mutational analysis of K-ras exon 1 and exon 2. RESULTS: In the SpCC group, cytokeratin positivity was significantly higher in epithelial areas (52.2%) than in spindle cell areas (16.1%), whereas vimentin was more positive in spindle cell areas (18.7%) than epithelial areas (2.7%). Cells intermediate between epithelial and spindle cell areas were consistently positive for both cytokeratin and vimentin. Cytokeratin was found to be significantly more positive in SCC (72.6%) than the squamous component and spindle cell component of SpCC. In this study, no mutation was detected in the K-ras gene of either the SpCC or SCC group. CONCLUSIONS: The spindle cell component of SpCC is intermixed with cells that are morphologically mesenchymal but express dual antigen-positivity characteristic of epithelial (cytokeratin) and mesenchymal (vimentin) cells. These, possibly, are cells in transition suggesting that SpCC may be a sarcomatous metaplasia of SCC.

Actins↗