Polynuclear Giant Cells Research Articles

Genetic and pharmacological inhibition of acid ceramidase prevents asymmetric cell division by neosis

Radiation treatment failure or relapse after initial response to chemotherapy presents significant clinical challenges in cancer patients. Escape from initial courses of treatment can involve reactivation of embryonic developmental stages, with the formation of polynuclear giant cancer cells (PGCCs). This strategy of dedifferentiation can insulate cancer cells from a variety of treatments and allows a residual subpopulation to reestablish tumors after treatment. Using radiation or docetaxel chemotherapy, we generated PGCCs from prostate cancer cells. Here, we show that expression of acid ceramidase (ASAH1), an enzyme in the sphingolipid pathway linked to therapy resistance and poor outcomes, is elevated in PGCCs. Targeting ASAH1 with shRNA or treatment with the ASAH1 inhibitor, LCL-521, did not impair the formation of PGCCs, but prevented the formation of PGCC progeny that arise through an asymmetric cell division called neosis. Similar results were obtained in lung cancer cells that had been exposed to radiation or cisplatin chemotherapy as stressors. In summary, our data suggest that endoreplication occurs independent of ASAH1 while neosis is ASAH1-dependent in both prostate and lung cancer cells. Because ASAH1 knockout is embryonic lethal but not deleterious to adult animals, targeting this enzyme has the potential to be highly specific to cells undergoing the dedifferentiation process to escape cancer treatments. Pharmacological inhibition of ASAH1 is a potentially powerful strategy to eliminate cells that could otherwise serve as seed populations for recurrence.

Analyzing the spatial positioning of nuclei in polynuclear giant cells

How cells establish and maintain a well-defined size is a fundamental question of cell biology. Here we investigated to what extent the microtubule cytoskeleton can set a predefined cell size, independent of an enclosing cell membrane. We used electropulse-induced cell fusion to form giant multinuclear cells of the social amoeba Dictyostelium discoideum. Based on dual-color confocal imaging of cells that expressed fluorescent markers for the cell nucleus and the microtubules, we determined the subcellular distributions of nuclei and centrosomes in the giant cells. Our two- and three-dimensional imaging results showed that the positions of nuclei in giant cells do not fall onto a regular lattice. However, a comparison with model predictions for random positioning showed that the subcellular arrangement of nuclei maintains a low but still detectable degree of ordering. This can be explained by the steric requirements of the microtubule cytoskeleton, as confirmed by the effect of a microtubule degrading drug.

Granulomatous lung diseases

Granulomatous lung disease is a heterogeneous group of diseases with different etiology, clinical symptoms and tissue damage, and different response to therapy. The prevalent histological sign of granulomatous lung disease is granuloma which is the clinical and morphological entity of this disease. The aim of this review was to describe a diversity of granulomatous diseases, key morphological features of infectious and non-infectious granulomatosis, and a diagnostic approach. Granuloma is a result of chronic inflammation involving cells of macrophage system and other inflammatory cells. Antigens activate T-lymphocytes, macrophages, epithelioid cells and polynuclear giant cells which form granuloma. Also, granuloma contains the extracellular matrix that is produced by fibroblasts and is intended to isolate the antigen. Granulomas could be infectious and non-infectious but, according to recent findings, microorganisms could cause granuloma formation in cases considered as non-infectious diseases. Therefore, sometimes it is difficult to estimate infectious or non-infectious origin of the disease.

Research of the expression of subchondral bone of Indian hedgehog with early experimental osteoarthritis induced by mechanical stress

Objective: To investigate the the expression of subchondral bone of Indian hedgehog(Ihh) with early experimental osteoarthritis induced by mechanical stress. Methods: The animals were equally divided into two groups: experimental group(E-group, n=15) and control group(S-group, n=15). The right knee joints of E-group underwent surgery, which involved in both medial collateral ligament (MCL) transaction and medial meniscectomy, while the control group was only carried out with a sham operation.The rats were killed at 1, 2 and 4 weeks postsurgery to obtain the right knee joints. Immunostaining and immunofluorescence double staining were performed to evaluate the expression of Ihh in subchondral bone, respectively. Results: The polynuclear giant cells in the subchondral bone of E-Group expressed Ihh in their cytoplasm 1 and 2 weeks post-surgery, except for 4 week, while those of S-Group appeared negative at all three time points postsurgery. There is statistically difference between the mean density of positive area of Ihh in sections of E-group and S-group both in 1 week (E-group: 0.351+ 0.086, S-group: 0.153±0.017, P<0.05) and 2 weeks (E-group: 0.303±0.026, S-group: 0.176±0.013, P<0.05), but without statistically difference in 4 weeks (E-group: 0.092±0.033, S-group: 0.136±0.014, P>0.05) post surgery. Trap positive giant cells in subchondral bone of E-group were also found Ihh positive, which indicated expression of Ihh in osteoclast . Conclusion: Ihh maybe play an important role in pathogenesis of early experimental osteoarthritis.

Clinical analysis of 10 patients with subcutaneous panniculitis-like T cell lymphoma

This study was purposed to evaluate the clinical and pathological features, prognosis of patients with subcutaneous panniculitis-time T cell lymphoma (SPTCL). The clinicopathologic features, immunophenotypes and treatment of 10 SPTCL patients which confirmed by pathology were analyzed retrospectively. The results showed that the main clinical manifestations of SPTCL were the single or multiple subcutaneous nodules. Of them 8 cases were found with recurrent high fever, weight loss, injury of liver function, bone marrow involvement and pancytopenia. This disease rapidly advanced. Pathologically, atypical large, medium-size and small-lymphocytes rounded the lipocytes look like rosettes. The reactive proliferation of histiocytes accompanied by phagothrocytic phenomena, polynuclear giant cells and granulomatous reaction. The tumor cells infiltrated into the lipolubuls. This lymphoma expressed the cytotoxic T-cell immunophenotype. CHOP regimen was the most common chemotherapy regimen used. 60% patients achieved a good initial response to chemotherapy. 3-year survival was 10%, with median survival time of 10 months. It is concluded that SPTCL is a specific type of lymphoma involving primarily in subcutaneous fatty tissues, most cases of SPTCL display an aggressive course, the disease may progress rapidly and accompanies with unfavorable prognosis. And the prognosis is poor in SPTCL patients with hemophagocytic syndrome. but the allo-HSCT can improve the outcome of this disease.

Comparative aspects of malignant cells in Hodgkin's granuloma in dogs.

Manifestation of Hodgkin’s malignant disease in dogs has a low incidence in Romania.Detailed cyto-morphological analysis of canine Hodgkin’s malignant granuloma, is particularlyimportant, as it can avoid some diagnosis errors, in a significant number of anatomical and clinicalforms of cancer disease with giant cells. It shows some representative images and details ofcomparative diagnosis and specific comment. There can be noticed that mono or polynuclear giantcells in dogs are associated with malignant cells in different locations, while in Hodgkin’s disease theyare placed exclusively in malignant granuloma. Diagnostic errors that can occur are discussed,according to the presented images.

A complex pattern of chemokine receptor expression is seen in osteosarcoma

BackgroundOsteosarcoma is the most frequent bone tumor in childhood and adolescence. Patients with primary metastatic disease have a poor prognosis. It is therefore important to better characterize the biology of this tumor to define new prognostic markers or therapeutic targets for tailored therapy. Chemokines and their receptors have been shown to be involved in the development and progression of malignant tumors. They are thought to be active participants in the biology of osteosarcoma. The function of specific chemokines and their receptors is strongly associated with the biological context and microenvironment of their expression. In this report we characterized the expression of a series of chemokine receptors in the complex environment that defines osteosarcoma.MethodsThe overall level of chemokine receptor mRNA expression was determined using TaqMan RT-PCR of microdissected archival patient biopsy samples. Expression was then verified at the protein level by immunohistochemistry using a series of receptor specific antibody reagents to elucidate the cellular association of expression.ResultsExpression at the RNA level was found for most of the tested receptors. CCR1 expression was found on infiltrating mononuclear and polynuclear giant cells in the tumor. Cells associated with the lining of intratumoral vessels were shown to express CCR4. Infiltrating mononuclear cells and tumor cells both showed expression of the receptor CCR5, while CCR7 was predominantly expressed by the mononuclear infiltrate. CCR10 was only very rarely detected in few scattered infiltrating cells.ConclusionOur data elucidate for the first time the cellular context of chemokine receptor expression in osteosarcoma. This is an important issue for better understanding potential chemokine/chemokine receptor function in the complex biologic processes that underlie the development and progression of osteosarcoma. Our data support the suggested involvement of chemokines and their receptors in diverse aspects of the biology of osteosarcoma, but also contradict aspects of previous reports describing the expression of these receptors in this tumor.

A Newborn with Rash and Chorioretinitis

IU/mL (positive VZV IgG titer, >1 IU/mL). Both the mother and the newborn had a VZV IgM titer of 1 IU/mL). The IgG titers of the mother and the newborn child showed no change after 3 months. IgM antibodies against herpes simplex virus (HSV) and hepatitis C virus (HCV) were not detected either the mother or the newborn. VZV DNA was detected a liquor specimen by PCR. Vesicle swab specimens failed to reveal VZV, and the Tzanck test showed neither polynuclear giant cells nor intranuclear inclusions the vesicle fluid. In our opinion, these findings indicate that the vesicles and the exudative blistery erythema spanning the axillary cavum are associated with a delayed in utero healing process, and that the vesicles are not an expression of the florid, active rash typical of infection. The mother was treated with acyclovir, 700 mg iv q8h for 7 days, within 2 days after the onset of vesiculopapular exanthema. Soon after birth, the newborn was treated with acyclovir, 30 mg/kg/day, given 3 divided doses for 20 days. The term varicella embryopathy refers to the spectrum of fetal anomalies associated with maternal VZV infection during the first trimester of pregnancy. VE manifests as cutaneous scars, limb hypoplasia, muscle atrophy, malformation of the digits, psychomotor retardation, microcephaly, cortical atrophy, Horner syndrome, and various eye abnormalities, including cataracts, chorioretinitis (figure 2), and microphthalmos. Intrauterine growth retardation, motor and sensory deficits, as well as other minor abnormalities have also been described [1, 2]. Approximately 30% of affected infants die during the first months of life, and infants who survive may present with a variety of sequelae, including early leukemia or other malig-

Is the appearance of macrophages in pulmonary tissue related to time of asphyxia?

In order to connect the appearance of macrophages and giant cells in pulmonary tissue with the time of asphyxia the authors analyzed 50 asphyxiated human lungs paying their attention on the number of alveolar and interstitial macrophages and giant cells. They compared histological specimens of 25 asphixiated humans lungs following a slow asphyxia (30 min or more) with 25 histological specimens of asphyxiated human lungs following a rapid asphyxia (10–15 min). Alveolar and interstitial macrophages and giant cells per section, were considered and numbered. Controls were done on histological examination of traumatized lungs. In the pulmonary alveoli following on acute asphyxia there were 27.7±4.4 macrophages per section. Subjects dead after a slow asphyxiation showed 68.2±7.1 alveolar macrophages per section ( p<0.001). Interstitial macrophages were also frequently present. No differences are detectable in the number of polynuclear giant cells between rapidly and slowly asphyxiated human lungs. The number of alveolar and interstitial macrophages per section can be considered as a further histological evidence of a slow asphyxia and can differentiate a slow asphyxia from an acute one.

A CASE OF RECURRENT MALIGNANT PHYLLODES TUMOR-INDICATION FOR QUADRANTECTOMY-

A 26-year-old woman admitted to the hospital because of recurred tumor in the CD area of the right breast. She had been operated on twice for the primary and recurred breast tumors in the same area. After this admission for the re-recurred breast tumor, histological examination of the biopsy specimen indicated that the lesion was phyllodes tumor (borderline lesion). Quadrantectomy was performed keeping a wide extension of surgical margin but conserving the brest. Regarding the morphology of the tumor, papillary proliferation was observed in the cyst. Compared with the previous specimens from this patient, the interstitial cells in the present specimen showed more mitoses, marked nuclear atypism and the existence of polynuclear giant cells. Based on these histopathological findings, the patient was diagnosed as having a malignant phyllodes tumor. No oncocytes were observed in the remaining stump, and lymph node metastasis was not confirmed. Quadrantectomy may be regarded as an effective surgical treatment for phyllodes tumor.

Inhibition of growth and increase of acid phosphatase by testosterone on androgen-independent murine prostatic cancer cells transfected with androgen receptor cDNA.

Most androgen-unresponsive prostatic cancer cells are found to lack androgen receptor (AR). To clarify the role of AR in the process of the progression from androgen-dependent to androgen-unresponsive tumor, the AR gene was transfected into an AR-negative rat prostatic cancer cell line CUB-II. AR-transfectant cells expressed AR mRNA and showed binding to R1881. AR was found in nuclei of AR-transfectant cells by histochemical examination. Therefore, AR-transfectant cells were considered to contain functional AR. The growth of AR-transfectant cells was markedly inhibited in culture in the presence of testosterone, and the effect of testosterone was reduced by simultaneous addition of flutamide. Moreover, tumors inoculated with AR-transfectant cells in male mice showed much slower growth than those in females. The tumors of AR-transfectant cells in mice consisted of slightly larger spindle-shaped cells when compared to those of CUB-II cells. Moreover, AR-transfectant cells contained a few polynuclear giant cells. Since CUB-II cells contained acid phosphatase (AcP) activity, the addition of testosterone in culture increased AcP activity of AR-transfectant cells. It is concluded that resumption of androgen-dependent processes reduces the growth rate accompanying changes of phenotype.

Pulmonary giant cells and traumatic asphyxia.

A morphometrical analysis was performed to elucidate the significance of pulmonary polynuclear giant cells as a histological sign of asphyxiation. A total of 13 cases of homicidal strangulation of throttling, 8 cases of traumatic asphyxia due to chest compression and 10 control cases (cause of death: severe head injury, no signs of aspiration or other relevant pulmonary alterations, smokers and non-smokers) were investigated. The number of alveolar macrophages containing 1 or 2 nuclei and of polynuclear giant cells per microscopic field (0.000025 cm2) was estimated and a statistical evaluation was carried out. A considerable individual variation was observed in all groups with a tendency to higher numbers of cells in cases of smokers or advanced individual age. However, no significant differences were detectable in the content of alveolar macrophages and in particular of polynuclear giant cells between the asphyxiated individuals and the controls. Since polynuclear giant cells occurred in similar amounts in healthy, functionally normal lungs of non-asphyxiated individuals, the detection of such cells cannot be regarded as a reliable indicator for asphyxiation.

Age-related changes in blood concentrations of FSH, LH and testosterone and testicular morphology in a new rat sterile mutant with hereditary aspermia

A new rat mutant showing aspermia was investigated. Groups of 4-7 mutant male rats were killed at 3, 5, 10, 15 and 25 weeks of age. Examination by microscope showed apparent abnormalities in the seminiferous epithelium from 3 weeks of age onward. Inclusion-like bodies were observed in the cytoplasm of pachytene spermatocytes from 3 weeks old and instead of spermiation, polynuclear giant cells were formed within the seminiferous epithelium after 5 weeks of age. Histological analysis of seminiferous epithelium of adult mutant rats also showed a marked decrease in the number of preleptotene, leptotene and pachytene spermatocytes and tubules containing only spermatogonia and Sertoli cells in the seminiferous epithelium increased with age. However, the combination of other cellular elements of germ cells in the seminiferous epithelium was similar to that in normal rats and the distribution rate of these seminiferous tubules was close to that of normal rats, indicating that cyclicity of seminiferous epithelium was still maintained in the mutant rats despite the lack of spermiation. Plasma concentrations of FSH and LH were significantly higher in the mutant male rats than in normal male rats at 5 and 10 weeks of age onward, respectively. Plasma concentrations of testosterone were lower in the mutant male rats than in normal male rats. Silastic capsules containing testosterone were implanted into the unilateral testis of adult mutant male rats and animals were autopsied 5 weeks later. However, intratesticular administration of testosterone did not affect restoration of spermatogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Muscle Cell Damage Through Autoimmune Mechanism. Can cardiac proteins provoke autoimmune myocarditis?

In this paper, the ability of human cardiac myosin to provoke autoimmune myocarditis was investigated. Myosin fractions were immunized into A.SW. mice, Lewis rats or Hartley guinea pigs. All of the immunized rats displayed overt symptoms of myocarditis and, in a few cases, died from it. The hearts of these rats were enlarged and discolored. Histologically, the muscles of the heart were characterized by remarkable cell infiltration, extensive myofiber necrosis and the appearance of polynuclear giant cells. Neither mice nor guinea pigs showed such disease profile. In this novel experimental model, the disease state was transferable by T lymphocytes. Thus, cardiac myosin was shown to provoke muscle cell damage through a T cell mediated autoimmune process.

Quantification of Alpha-Fetoprotein and Beta-HCG in Testis Tumor Patients

Patients with testis tumor were investigated for serum and tissue levels of alpha-fetoprotein and beta-human chorionic gonadotropin (beta-HCG). The tissue immune peroxidase-antiperoxidase staining for the tumor marker was quantitated by computer-assisted immunohistophotometry and immuno-gamma ray histospectrometry. The results supported the general view that mostly polynuclear giant cells produce beta-HCG in 66% of nonseminoma cancer. This finding qualifies beta-HCG as relatively unspecific in the absence of chorioepithelial cells in the tumor. Discrepancies of tissue and serum beta-HCG values may be caused by deglycolysation of beta-HCG while penetrating the perivascular tissues. Alpha-fetoprotein (AFP) appears helpfully to discriminate the true seminoma cancer, which is constantly negative. Histologically pure seminoma which reacts for AFP therefore suggests sclerotic teratoma compartments. A constant finding is the significantly reduced synthesis rate of tumor markers in metastasis compared to primary tumor.

下がく悪性線維性組織球しゅ症例の臨床的，病理組織学的ならびに生化学的検討

Malignant fibrous histiocytoma of the oral region is rare. Clinical course, histopathological observations and biochemical analysis of malignant fibrous histiocytoma of the mandible in an 18-year-old male is reported.The clinical findings revealed rapid enlargement of two nodular tumors 5 cm and 3cm diameter, in the molar region of the right mandible and tender regional lymph nodes. Radiographically, separation of the wisdom tooth and the second molar tooth and an irregular radiolucent area reaching to the mandibular canal were shown. Segmentary resection of the mandible and radical neck dissection were carried out. Postoperative course of the patient was uneventful and no recurrence or metastasis was found after 2 years.Histopathologically, most of the tumor consisted of a highly myxoid tissue. In the myxoid area widely spaced spindle cells, pleomorphic cells and giant cells were arranged in a matrix.In electron microscopic examination, fibroblast-like cells, histiocyte-like cells and polynuclear giant cells were observed.By the biochemical methods, type I, III and V collagen were detected by the SDS-PAGE method. Dihydroxylysinonorleucine was found to be the major reducible cross-link in this collagen and its ratio to hydroxylysinonorleucine is 2.4. This suggested that the collagen is similar to the hard tissue collagen or at the young and growing stage. Pyridinoline and histidinoalanine were found to be the noreducible cross-link in this collagen.

Human lymphocyte transformation with virus antigens.

Lymphocyte transformation tests were carried out in patients with recurrent aphthae and control persons, using heat treated Herpesvirus hominis and adenovirus antigens of different types. From the virus antigens examined, only the Herpesvirus hominis and adenovirus type 1 antigens caused blastogenic transformation in higher rate in the lymphocyte cultures of aphthous patients, than in those of the control persons. Plasma cell reaction was observed with some adenovirus types, and the appearance of polynuclear giant cells was detected besides the lymphoblasts in the lymphocyte cultures of certain individuals examined.

Facial palsy in Hand-Schüller-Christian's disease.

HAND-Schuller-Christian's disease is a disseminated granulomatosis of unknown etiology. The clinical appearances are characterized by granulomas affecting mainly the skeletal system, especially the skull. The skin, the lymph node system, mucous membranes, and viscera may also be involved. The disease runs a typically chronic course with a tendency to remission. The histological appearance of the granulomas is fairly polymorphous. The cellular tissue is predominated, during the early stages, by reticulum cells, eosinophilic leukocytes, plasma cells, and polynuclear giant cells. At later stages there are foam cells containing cholesterol. The symptoms and signs are varied, but the otological signs occupy a preferential position, both by virtue of their common presence and their early appearance. Thus, many cases are seen first by the otologist (among the approximately 700 reported cases several have been published by otologists). I have1collected 500 cases from the literature and reviewed the manifold ear, nose, and

Response of the testes to social interaction among grouped chickens

The effects of social interaction on the adaptive response of the testes were studied by maintaining chickens in experimental heterosexual groups for periods of 12 to 30 weeks. Increases in group size resulted in an increase in social conflict within groups. This interaction was reflected by smaller testes among the grouped males when compared with isolated and heterosexually paired cocks. The number of birds within a group rather than density seemed to be the important factor in determining the intensity of social interactions. Thus, in groups where sufficient space was allotted for freedom of movement, the frequency of interactions and decrease in testicular weight was as great as among groups of the same size where density made social contacts unavoidable. Within the groups testes weights were correlated with social rank. The most dominant males were found to have the heaviest testes while the subordinate cocks had the lightest and, occasionally, atrophic testes. The smaller testes associated with increased group size and subordinate social rank were attributed to degenerative changes in the germinal epithelium of grouped subordinate cocks. The most frequently encountered testicular changes were the formation of polynuclear giant cells and associated degenerative lesions within the germinal epithelium. In a few subordinate males complete regression was observed in the germinal layer of the testes. These observations support the hypotheses that social conflict may be an important factor in determining the adaptive response of the testes of chickens. Certain features of this response suggest that domestic fowl provide a useful species for further studies of reproductive function as related to their characteristic social interaction.

Analysis of giant polynuclear cell formation caused by HVJ virus from Ehrlich's ascites tumor cells: I. Microscopic observation of giant polynuclear cell formation

When an HVJ-ETC mixture is kept at 37 °C with shaking, polynuclear giant cells appear within 30 min. The process was observed under phase contrast and electron microscopes. By the addition of the virus at 4 °C the cells were strongly agglutinated and many virus particles were adsorbed onto the cell surface, especially onto microvilli. During incubation at 37 °C the virus particles disappeared from the cell surface and the large aggregates were dispersed into a number of smaller ones. At that time the degenerated cells which were contaminants from the original cell sample, and were included in the large aggregates, were rejected from the aggregated cells which are transformed into giant cells later. Then the opposed cells in the smaller aggregates fused together and after 30 min incubation typical giant cells appeared. The giant cells are due to fusion of the cells themselves. Two characteristic regions were observed in the reacting cells; one may be a part of the enfolded cell surface, and the other is a complexed projection on the cell surface at the contact point of opposed cells.