Biomedical subjects

B Lifschitz-Mercer

Publications and source records attributed to B Lifschitz-Mercer.

At least 19 recordsLinked to original sources

PubMed1999

Exposure of human peripheral blood mononuclear cells (PBMC) to hydrostatic pressure increases their proliferative response to phytohemagglutinin A (PHA) and anti-CD3 antibody.

In the present study we show that a brief exposure of human PBMC to hydrostatic pressure (HyP) increased their proliferative response to PHA and anti-CD3 antibody, assessed by DNA synthesis. The effect of HyP was most prominent at 400 atmospheres of HyP followed by 600 and 200 atmospheres. At any pressure level, the highest effect of HyP was noted when employing PHA and anti-CD3 antibody at 10(-2) dilution. When PBMC were exposed to 400 atmospheres HyP, maximal effect was achieved at 20 minutes of exposure. The highest effect of HyP on DNA synthesis was noted at 48 and 72 hours of incubation with PHA, when exposing cells to pressure for 20 minutes at 400 atmospheres. Exposure of PBMC under similar conditions for 40 minutes, caused an increase in DNA synthesis only at 48 hours incubation with PHA. These results demonstrate that exposure of human PBMC to HyP increases their proliferative response to different polyclonal activators. The possible mechanisms involved in this phenomenon are discussed.

Antibodies↗

PubMed1998

Human tumor cells, modified by a novel pressure/crosslinking methodology, promote autologous lymphocyte proliferation and modulate cytokine secretion.

Hydrostatic pressure (P) combined with membrane protein crosslinking (CL) by adenosine dialdehyde (AdA) can render tumor cells immunogenic. We have recently shown that PCL treatment of murine tumor cells augmented the presentation of MHC-restricted tumor-associated antigens and enhanced cell-mediated immunity. In cancer patients inoculated with autologous PCL-modified tumor cells, a significant delayed-type hypersensitivity response was elicited. Since the balance between cell-mediated immunity and humoral immunity is reciprocally controlled by immunoregulatory cytokines, we have examined the proliferative response and cytokine secretion pattern in cultures of human peripheral blood mononuclear cells (PBMC) stimulated by autologous PCL-modified and unmodified tumor cells. These tumor cells were obtained from freshly resected tumor tissue of 16 patients with colon (8), lung (4) and renal (4) carcinomas. The results demonstrated that PCL-modified tumor cells promoted an increase in PBMC proliferation in 5 out of 8 (63%), 1 out of 4 (25%) and 4 out of 4 (100%) colon, lung and renal cell carcinomas. Fourteen of the above cultures were also analyzed for the secretion of interleukin-10 and interferon-gamma. Overall, a substantial decrease in IL-10 secretion was detected in 9 out of 14 (64%) cultures while a reciprocal increase in interferon-gamma secretion was noted in 8 out of 14 (57%) cultures. Our results confirmed that PCL-modified human tumor cells of different etiologies can modulate the pattern of cytokines released from stimulated autologous lymphocytes. Such a procedure could prove valuable in the production of autologous tumor vaccines.

Carcinoma↗

PubMed1998

Primary angiosarcoma of the ovary: a clinicopathologic, immunohistochemical and electronmicroscopic study.

The present report of a 25 year old woman with a primary ovarian angiosarcoma is supplemented by histochemical and ultrastructural studies and reviews the literature of this extremely rare neoplasm. Since this ovarian tumor, especially in young women, may constitute a diagnostic pitfall, problems relating to differential diagnosis are emphasized. Although the origin of this neoplasm appears to occur most likely from the rich ovarian vasculature, other less conventional histogenetic theories such as a possible origin in mixed mullerian tumor, in teratoma or in other ovarian germ cell tumors have also been proposed and are considered in this paper.

Actins↗

PubMed1998

Costimulatory activity of inactivated influenza virus in response of human peripheral blood mononuclear cells to phytohemagglutinin A and anti-CD3 antibody.

We tested the effect of inactivated influenza A virus on the response of human T lymphocytes to several stimuli. Our results demonstrate that the response to both phytohemagglutinin A (PHA) and anti-CD3 was substantially enhanced by pre-exposure of peripheral blood mononuclear cells (PBMC) to heat-inactivated viral particles, whereas no effect was noted on the proliferative response of PBMC to IL-2. In addition to cell proliferation, exposure of PBMC to viral particles increased the secretion of interferon (IFN)-gamma during stimulation with anti-CD3 antibody and PHA. The costimulatory effect of influenza A virus was reduced by 40% in the presence of 0.1 mM sialic acid. The possible mechanisms involved in the costimulatory effects of influenza A virus are discussed.

Antibodies, Monoclonal↗

PubMed1998

Angiosarcoma of the ovary: clinicopathologic and immunohistochemical analysis of four cases with a broad morphologic spectrum.

Angiosarcoma most frequently occurs in the skin of the head and neck region of elderly persons, lymphedematous limbs, or in deep soft tissue but only rarely has been described to occur in the female genital tract. Four cases of angiosarcoma of the ovary are described herein. They occurred in patients 25 to 42 years old (median, 31 years). The most common clinical presentation was abdominal pain. All of the tumors were unilateral, hemorrhagic, and ranged from 3.5 cm to 14 cm (median, 13 cm). The histologic appearance of the tumors was varied, and often the vascular nature of the tumor was not apparent immediately. Some of the tumors had a fascicular growth pattern composed of spindle-shaped cells with ovoid nuclei and ample eosinophilic cytoplasm closely mimicking leiomyosarcoma. Other tumors resembled ovarian yolk sac tumor with a reticular growth pattern, whereas, in other areas, cystic structures lined by hobnailed hyperchromatic enlarged nuclei simulated clear cell carcinoma of the ovary. Despite these misleading morphologic findings, all cases were characterized, at least focally, by vasoformative channels or discrete cytoplasmic vacuoles, and all were immunoreactive for vascular markers. Two patients with spread of tumor outside of the ovary died 1 month and 2 years after initial diagnosis, respectively. Two patients with tumor confined to the ovary are alive without evidence of disease 3 and 14 months after diagnosis, respectively. The differential diagnosis of this unusual neoplasm is discussed, and the literature is reviewed.

Adult↗

PubMed1998

The effect of interferon-gamma and tumor necrosis factor-alpha on the expression of ICAM-1 and HLA-DR molecules on cells of a human germ cell neoplasm and their susceptibility to lysis by lymphokine-activated killer cells.

The ICAM-1 molecule plays a role in the interaction of NK cells with a variety of tumor cells, including carcinoma, melanoma and glioblastoma cells. In the present study, we analyzed the effect of IFN-gamma and TNF-alpha on both the expression of HLA-DR and ICAM-1 molecules on HGCN (Germa-2), and on their susceptibility to lysis by LAK cells. Our results show that 1,000 U/ml IFN-gamma induced a substantial increase in the expression of both ICAM-1 molecules and HLA-DR on the cell surface, while the effect of TNF-alpha on the expression of these molecules was substantially less prominent. When Germa-2 cells, previously exposed to 1,000 U/ml IFN-gamma, were employed as target cells in a 4-hour 51Cr release assay, a statistically significant increase in the lysis by LAK cells was noted. These results show that in the presence of IFN-gamma, Germa-2 tumor cells undergo modulation which affects both the expression of ICAM-1 and HLA-DR molecules as well as their susceptibility to lysis by LAK cells.

Cytotoxicity Tests, Immunologic↗

PubMed1997

Anti-tumor necrosis factor-alpha improves myocardial recovery after ischemia and reperfusion.

OBJECTIVES: This study sought to assess the importance of locally released or paracrine myocardial tumor necrosis factor-alpha (TNF-alpha) in the evolution of postischemic myocardial dysfunction and to use immunohistochemical studies to localize TNF-alpha within the myocardium. BACKGROUND: TNF-alpha is implicated as a systemic mediator in the development of myocardial ischemia-reperfusion injury by promoting leukocyte myocardial infiltration, and it has been shown to originate from noncardiac peripheral mononuclear cells. We have recently documented in a blood-free environment the release of TNF-alpha from the ischemic-reperfused myocardium. METHODS: Isolated rat hearts undergoing 1 h of global cardioplegia-induced ischemia and 30 min of reperfusion were investigated with use of the modified Langendorff model. Hearts were randomly divided into three subgroups: group A, control group; and groups B and C, isolated hearts receiving cardioplegic solution containing monoclonal hamster antimurine TNF-alpha antibodies (group B) or hamster IgG (group C). RESULTS: Significant amounts of TNF-alpha were detected in group A and group C effluent on 1 min of reperfusion (752 +/- 212 and 958 +/- 409 pmol/ml, respectively). However, in group B, TNF-alpha was below detectable levels. In this group, postischemic left ventricular peak systolic pressures, first derivative of the rise in left ventricular pressure (dP/dtmax), pressure-time integral, coronary flow and O2 consumption improved (analysis of variance [ANOVA] p < 0.0001 for all variables) compared with values in groups A and C; creatine kinase levels decreased (p < 0.005); and myocardial structure was preserved. Immunohistochemical staining localized TNF-alpha to cardiac myocytes and to endothelial cells. CONCLUSIONS: Anti-TNF-alpha neutralizes local TNF-alpha release from cardiac myocytes after ischemia and improves myocardial recovery during reperfusion, indicating that postischemic paracrine TNF-alpha release plays an active role in myocardial dysfunction.

Animals↗

PubMed1997

Metastasizing placental site trophoblastic tumor: immunohistochemical and DNA analysis. 2 case reports and a review of the literature.

Placental-site trophoblastic tumor (PSTT) is a rare form of gestational trophoblastic neoplasia. The clinical behaviour of PSTT is usually benign, but sometimes it can be highly malignant with late recurrence and metastasis. We describe two cases of PSTT with pulmonary metastasis in patients aged 35 and 29 years respectively. The mitotic rate was elevated to 9 and 13 mitotic figures per 10 high-power fields respectively. Immunohistochemical staining showed a predominance of human placental lactogen (hPL) positive cells when compared with human chorionic gonadotropin (hCG) reactive cells in one case, and a reverse pattern in the other one. DNA measurement in one case showed an aneuploid tumor with a tetraploid DNA peak. The clinical behaviour of PSTT remains unpredictable, and there are no reliable means of predicting clinical outcome.

Adult↗

PubMed1997

Expression of the adherens junction protein vinculin in human basal and squamous cell tumors: relationship to invasiveness and metastatic potential.

The acquisition of an invasive or metastatic phenotype in malignant neoplasms is often correlated with reduced cellular adhesiveness. We investigated the expression of the adhesion-associated cytoplasmic protein, vinculin, in normal and neoplastic human squamous epithelia, as well as in metastases of squamous cell carcinomas, and correlated the results with invasiveness and metastatic potential. Tissue samples from various tumors were examined, including basal cell carcinomas (BCC), keratoacanthomas, and squamous cell carcinomas (SCC). In addition, lymph node metastases from nine of the SCC were tested in this study. Our results indicate that most BCC, keratoacanthomas, and in situ SCC display strong positive staining for vinculin. The level of immunolabeling for vinculin and its pattern of distribution in the low malignant, nonmetastasizing lesions was similar to those observed in normal squamous epithelia. In contrast, in SCC, which are invasive and possess metastatic potential, as well as in their metastases, vinculin labeling was negative or poor, irrespective of their degree of differentiation. In conclusion, poor vinculin labeling in tumors of squamous epithelial origin examined here appears to be related to the metastatic potential of the tumor. Vinculin immunostaining of primary tumors originating in stratified squamous epithelia may thus be of value in helping to determine the metastatic potential of these neoplasms.

Basal Cell Carcinoma↗

PubMed1997

Influenza A virus affects the response of human peripheral blood mononuclear cells to phytohaemagglutinin A by altering the cytoskeleton.

In the present study, we demonstrate that the infection of human peripheral blood mononuclear cells (PBMC) with influenza A virus caused changes in intracellular fluorescein fluorescence polarization (IFFP) which, as previously described, reflect alterations in the polymerization of the cytoskeleton. Kinetic measurements revealed two cycles of an approximate 10% decrease in IFFP within 3.5 and 5 h after infection. Infection win influenza A virus also altered the response of PBMC to phytohaemagglutinin (PHA), which was manifested as changes of 5.3 and 4% in IFFP at 1 and 2 h after infection, respectively. the changes in IFFP correlated with DNA synthesis measured 72 h after exposure to PHA. These results show the ability of IFFP measurements to identify early intracellular metabolic events induced in virus-infected cells.

Cell Division↗

PubMed1997

Infection of K562 cells with influenza A virus increases their susceptibility to natural killer lysis.

Natural killer (NK) cells play a role in the natural immunity against tumor cells. In the present study, we demonstrate that infection of the NK-sensitive tumor cell line K562 with influenza A virus caused a substantial increase in lysis of up to sevenfold when compared to noninfected cells. Similar to NK cells, IL-2-activated killer cells exhibited higher lytic activity against virus-infected K562 cells. This effect of the virus correlated with the increase in the expression of intracellular adhesion molecule-1 (ICAM-1) on K562 cells. Changes in the susceptibility to NK lysis were accompanied by alterations, within minutes, in the cytoskeleton as detected by intracellular fluorescein fluorescence polarization measured on the Cellscan, a static cytometer. The possible role of iCAM-1 and the cytoskeleton in the cytotoxic response of NK cells is discussed.

Cytotoxicity, Immunologic↗

PubMed1997

Endometrial pathology.

The current literature on endometrial neoplasia deals with proliferative lesions such as endometrial proliferation in early pregnancy, atypical polypoid adenomyofibromata and their possible relationship to carcinoma, and histological grading of endometrial cancer with emphasis on nuclear grading and subtypes of endometrial cancer including the newly described intestinal and hepatoid types. Recent publications dealing with p53 protein, genetic studies, and nucleolar organizer regions are of interest but have provided no striking new insight into endometrial neoplasia. Angiogenesis has appeared for the first time in the literature in connection with endometrial neoplasia. Tamoxifen continues to occupy an important place in the literature, and endometrial adenosarcoma has been identified recently as one of the myriad of lesions which patients treated with tamoxifen are prone to develop.

Antineoplastic Agents, Phytogenic↗

PubMed1996

Palmar fasciitis and polyarthritis associated with ovarian carcinoma in a young patient. A case report and review of the literature.

Palmar fasciitis and polyarthritis (PFPA) is an uncommon syndrome characterized by progressive and extensive rheumatic disease. It has usually been associated with neoplasms, most commonly in elderly patients, preceding or accompanying the diagnosis of malignancy. We report a case of a 25-year-old patient with severe deforming PFPA preceding the diagnosis of carcinoma of the ovary. The histopathological findings of diffuse fibrosis, connective tissue proliferation and vasculitis with C3 and IgM deposits in subcutaneous tissue and synovia may further clarify the possible pathogenesis of this unique syndrome.

Adult↗

PubMed1996

Decrease of intracellular fluorescein fluorescence polarization (IFFP) in human peripheral blood lymphocytes undergoing stimulation with phytohaemagglutinin (PHA), concanavalin A (ConA), pokeweed mitogen (PWM) and anti-CD3 antibody.

In the present study we describe the induction of changes in intracellular fluorescein fluorescence polarization (IFFP) in lymphocytes undergoing activation with a variety of stimulants. These stimulants included the lectins phytohaemagglutinin (PHA), concanavalin (ConA), pokeweed mitogen (PWM) and anti-CD3 antibody. Changes in IFFP were detected in individual cells using the Cellscan apparatus. Our results show that by employing mitogenic concentrations of PHA, as revealed in a [3H]-thymidine incorporation assay, a decrease in the IFFP in human peripheral blood lymphocytes (PBL) occurred within 40 min. ConA and anti-CD3 affected similarly IFFP, whereas PWM, a B lymphocyte lectin, had no effect on IFFP at the concentrations employed. Kinetic analysis revealed that changes in IFFP occurred within 20-40 min after exposure to the stimulants and lasted for 24 h. Our results show that stimulants which activate CD3+ lymphocytes caused immediate changes in IFFP, in an enriched population of human PBL. The possible mechanisms involved in IFFP modulation following exposure to selected stimulants are discussed.

Antibody Specificity↗

PubMed1996

Effect of interleukin-1 alpha, interleukin-1 beta and tumor necrosis factor-alpha on the intracellular fluorescein fluorescence polarization of human lung fibroblasts.

In the present study we aimed to detect early intracellular changes in the cytoplasmic matrix induced in human, pulmonary-derived fibroblasts following exposure to interleukin (IL)-1 alpha, IL-1 beta and tumor necrosis factor-alpha. Such changes were detected by measuring intracellular fluorescein fluorescence polarization (IFFP) using the Cellscan apparatus. IFFP measurement was selected in our study since it has been shown to reflect the microviscosity of the cytoplasmic matrix. Significant reductions (> or = 5%) in the IFFP were induced in fibroblasts by all the cytokines employed. The effect of cytokines on IFFP was achieved at concentrations of 5-10 ng/ml of the cytokines. The reduction in IFFP, following stimulation with the cytokines, was detected as early as 20 min after exposure to the cytokines, lasted at least 40-60 min after exposure to IL-1 alpha and IL-1 beta, and was inhibited by vinblastine, an inhibitor of the polymerization of microtubules. Our results show that IFFP measurements by the Cellscan may reveal rapid intracellular changes occurring in the cytoskeleton components of activated cells.

Cytochalasin B↗

PubMed1996

Surface projection of murine major histocompatibility determinants induced by hydrostatic pressure and cytokines.

Augmentation of surface presentation of the major histocompatibility complex (MHC) is a leading trend for preparation of tumor vaccines. Exposure of weakly immunogenic tumor cells, such as murine B16 melanoma, to hydrostatic pressure (P) in the presence of the membrane-impermeable protein crosslinker (CL) 2',3'-adenosine dialdehyde, was previously shown to induce a substantial increase in surface presentation of MHC molecules. When B-16 melanoma cells, used here as a model, were first treated for 72 h with interferon-gamma or tumor necrosis factor-alpha at concentrations of 10 and 100 units/ml, respectively, followed by application of pressure and cross-linking (PCL), the surface presentation of H2b molecules increased by 40% compared to treatment with cytokines alone, and by up to 1,700% when compared to treatment with PCL alone. Neither P nor CL alone enhanced the MHC presentation when cells were pretreated with these cytokines. The changes in MHC observed after the cytokine treatment were transient and decayed within several hours. However, the changes induced by the sequential treatment with cytokines and PCL were sustained for at least 96 h post-PCL which is of prime importance for immunogenic expression. A series of analogous experiments in the presence of cycloheximide indicated that approximately 50% of the observed PCL-induced increase in MHC projection originates from protein synthesis while the other 50% corresponds to passive translocation of MHC compartments. B16 melanoma cells, modified by the sequential treatment of cytokines and PCL, proved to be substantially more immunogenic by an in vitro sensitization assay than cells treated by either one of these treatments alone. These results may provide a guideline for the preparation of tumor vaccines which could be applied in immunotherapy treatment of cancer.

Animals↗

PubMed1996

Inhibition of mitogen-induced changes in intracellular fluorescein fluorescence polarization of human peripheral blood lymphocytes by colchicine, vinblastine and cytochalasin B.

We have previously reported that the exposure of human peripheral blood lymphocytes (PBL) to a variety of stimulants caused rapid changes in intracellular fluorescein fluorescence polarization (IFFP) in the activated cells. In the present study we further analyzed possible mechanisms responsible for the changes in IFFP in PBL exposed to phytohaemagglutinin (PHA) and anti-CD3 antibody. By employing several agents which are known to affect the polymerization of the cytoskeleton we showed that both cytochalasin B, which regulates the microfilaments structure, and vinblastine and colchicine, which affect the microtubules, completely abolished the changes induced in IFFP of human PBL by both PHA and anti-CD3. This effect was dose dependent and was noted at concentrations ranging from 10 to 100 microM of cytochalasin B and 10 microM of vinblastine and colchicine. The effect of these cytoskeleton modulators occurred within 20 minutes after the initiation of activation with PHA. Our results indicate that activation with PHA and anti-CD3 causes early changes in the microtubules and microfilaments components of the cytoskeleton. The possible application of IFFP measurement in analyzing early changes in the cytoskeleton following cell activation is discussed.

Colchicine↗

PubMed1996

Hyperestrogenemia and presence of estrogen receptors associated with an epithelial ovarian tumor of low malignant potential.

An 80-year-old woman presented with breast congestion, tenderness and pain. Mammography was normal. Circulating estradiol was markedly elevated, while LH and FSH were low. Pelvic examination and imaging revealed an ovarian mass which was extirpated during total abdominal hysterectomy and bilateral salpingo-oophorectomy. Histopathology revealed an ovarian mucinous cystadenocarcinoma of low malignant potential, stage 1. The tumor was positively stained for estrogen receptors. Estradiol levels returned to normal post-operatively, with a corresponding adjustment of LH/FSH. Possible autocrine steroid production is discussed.

Aged↗