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Y Keisari

Publications and source records attributed to Y Keisari.

At least 19 recordsLinked to original sources
PubMed2002

Laser activated fluorescence measurements and morphological features: an in vivo study of clearance time of fluorescein isothiocyanate tagged cell markers.

Fourteen BALB/c mice were divided into two groups. One group served as the control and the second group was injected with a squamous cell carcinoma cell line to the tongue. After tumor development (1-4 weeks), mice were injected with a FITC conjugated CD3 marker to their tongues. Immediately after the marker injection, the clearance of the marker was measured using a laser spectroscopy system. The markers were excited by an argon laser at 488 nm and the fluorescence signal was measured as a function of time. A biopsy was taken from every mouse after the procedure and the excised tissue was histologically evaluated. Analysis of clearance times revealed a second order exponential decay for both groups with a slower pace of signal clearance for the sick mice.

Animals↗
PubMed2001

Surfactant protein D enhances phagocytosis and killing of unencapsulated phase variants of Klebsiella pneumoniae.

Pulmonary surfactant protein D (SP-D) is a collagenous C-type lectin (collectin) that is secreted into the alveoli and distal airways of the lung. We have studied the interactions of SP-D and alveolar macrophages with Klebsiella pneumoniae, a common cause of nosocomial pneumonia. SP-D does not agglutinate encapsulated K. pneumoniae but selectively agglutinates spontaneous, unencapsulated phase variants, such as Klebsiella strain K50-3OF, through interactions with their lipopolysaccharides (LPS). These effects are calcium dependent and inhibited with maltose but not lactose, consistent with involvement of the SP-D carbohydrate recognition domain. Precoating of K50-3OF with SP-D enhances the phagocytosis and killing of these organisms by rat alveolar macrophages in cell culture and stimulates the production of nitric oxide by the NR-8383 rat alveolar macrophage cell line. SP-D similarly enhances the NO response to K50-3OF LPS adsorbed to Latex beads under conditions where soluble LPS or SP-D, or soluble complexes of SP-D and LPS, do not stimulate NO production. Our studies demonstrate that interactions of SP-D with exposed arrays of Klebsiella LPS on a particulate surface can enhance the host defense activities of alveolar macrophages and suggest that activation of macrophages by SP-D requires binding to microorganisms or other particulate ligands. Because unencapsulated phase variants are likely to be responsible for the initial stages of tissue invasion and infection, we speculate that SP-D-mediated agglutination and/or opsonization of K. pneumoniae is an important defense mechanism for this respiratory pathogen in otherwise healthy individuals.

Agglutination↗
PubMed2001

Anti-cancer activities of hypericin in the dark.

The potent photodynamic properties of hypericin (HY) elicit a range of light-dependent virucidal and tumoricidal activities. Yet, a relatively low reduction/oxidation potential endows HY with electron accepting and donating properties enabling it to act as both an oxidizing and a reducing agent. HY can thus compete as an electron acceptor from bioenergized reduction/oxidation reactions generating its excitation energy for biological activities from physiological reduction/oxidation reactions in the absence of light. Our studies show that HY can inhibit the growth of highly metastatic murine breast adenocarcinoma and squamous cell carcinoma tumors in culture. Furthermore, we show that HY can interfere with the growth of these tumors in mice reducing tumor size and prolonging animal survival in complete absence of light. While there is no evidence that HY induces apoptosis in these cells in the dark, 3H-thymidine incorporation into DNA was significantly reduced indicating effects that are apparently cytostatic in nature compared to the cytocidal effects of HY with light.

Animals↗
PubMed2001

Surfactant protein D-coated Klebsiella pneumoniae stimulates cytokine production in mononuclear phagocytes.

Encapsulated Klebsiella pneumoniae strains K21a, K10, and K50, all of which contain dimannose sequences in their capsular polysaccharides that are recognized by the mannose receptor of macrophages, stimulated interleukin secretion and cytokine mRNA expression by human monocyte-derived macrophages. By contrast, the corresponding unencapsulated phase variants and the K2 strain, which lack the dimannose sequence, did not. Coating of unencapsulated phase variants of Klebsiella strains with surfactant protein (SP)-D resulted in marked stimulation of cytokine mRNA accumulation. The induction of cytokine mRNA via the mannose receptor occurred only in monocyte-derived macrophages, whereas that caused by SP-D-coated Klebsiella strains occurred in both macrophages and peripheral-blood monocytes. The results suggested that innate immunity against pulmonary pathogens might be mediated by SP-D, which acts as an opsonin to enhance the interaction of macrophages with unencapsulated phase variants originating from the upper respiratory tract, and by macrophage mannose receptors, which recognize encapsulated variants expressing capsular dimannose residues.

Cytokines↗
PubMed2001

Inhibition of antibody-dependent stimulation of lipoteichoic acid-treated human monocytes and macrophages by polyglycerolphosphate-reactive peptides.

By itself, lipoteichoic acid (LTA) obtained from S. pyogenes, S. aureus, or E. hirae poorly stimulated cytokine production by macrophages, whereas in the presence of anti-polyglycerol phosphate (PGP), the cells secreted significant amounts of IL-6. Two peptides constructed from the deduced sequence of the selected anti-PGP phage-antibody's complementary-determining region 3 of the variable heavy chain (V(H)-CDR3) reacted specifically with PGP. The monomeric form of the peptides markedly inhibited cytokine production by macrophages pretreated with LTA and anti-LTA. In contrast, the polyvalent form of biotinylated peptides complex with streptavidin-induced cytokine production by the LTA-treated macrophages. The data taken together support the concept that cross-linking of macrophage-bound LTA by anti-PGP is required for cytokine release by these cells. Importantly, these studies identified small, PGP-reactive peptides as potential tools in reducing this proinflammatory process.

Amino Acid Sequence↗
PubMed2000

Effects of photodynamic therapy with hypericin in mice bearing highly invasive solid tumors.

The tumoricidal properties of photodynamic therapy (PDT) with hypericin (HY) were evaluated in a highly metastatic adenocarcinoma (DA3Hi) and anaplastic squamous cell carcinoma (SQ2) tumors in vivo. Photosensitization of the tumor site with hypericin (HY-PDT) reduced primary tumor development and significantly prolonged the survival of tumor-bearing (TB) mice. Of these two tumors the squamous cell carcinoma emerged as more sensitive to HY-PDT compared with DA3Hi adenocarcinoma both in vitro and in vivo. HY-PDT caused extensive tumor necrosis that was followed by local, intratumoral, and systemic inflammatory reactions. Analyses of cytokine mRNA profiles reveal increases in mRNA levels of expression confined to inflammation-related cytokines both within the tumor and also systemically (measured in spleens). However, there was no evidence for any HY-PDT-induced antitumoral immune reactions. Our results suggest that PDT with hypericin can be considered as a supplementary treatment in the management of some invasive and metastatic cancers such as squamous carcinoma and similar tumors.

Adenocarcinoma↗
PubMed1999

Quantitative analysis of IgG class and subclass and IgA serum response to Shigella sonnei and Shigella flexneri 2a polysaccharides following vaccination with Shigella conjugate vaccines.

It has been recently reported that a conjugate vaccine composed of the O-specific polysaccharide of S. sonnei bound to Pseudomonas aeruginosa recombinant exoprotein A (rEPA) conferred 74% protection against S. sonnei shigellosis. In the present study affinity purified Shigella antibodies were used as standards to quantify and characterize the serum antibody response to vaccination with Shigella sonnei or Shigella flexneri 2a polysaccharide conjugated to rEPA. The geometric mean concentrations of antibodies at the pre-vaccination stage were 3.8 microg/ml for IgG anti-S. sonnei LPS and 11.26 microg/ml for IgG anti-S. flexneri 2a LPS. Vaccination with S. sonnei-rEPA and S. flexneri 2a-rEPA induced the production of specific IgG antibodies to levels of 115.8 microg/ml and 126.5 microg/ml, respectively. The levels of specific antibodies above the pre-vaccination values persisted for at least 2 years. The IgG response to S. flexneri 2a-rEPA conjugate was almost entirely represented by the IgG2 subclass. The concentration of IgG1 anti-S. sonnei LPS was significantly higher than that of IgG2 14 days after vaccination with the homologous conjugate, but decreased to similar levels to those of IgG2 6, 12 and 24 months after immunization. Since the only difference between the S. sonnei and S. flexneri 2a conjugates lies in the different polysaccharides of the two Shigella serogroups (the protein rEPA, is identical in both cases), it follows that the different pattern of IgG subclass response is a result of the different structures of the two O-polysaccharides of S. sonnei and S. flexneri 2a.

Adolescent↗
PubMed1999

THF-gamma 2-mediated reduction of pulmonary metastases and augmentation of immunocompetence in C57BL/6 mice bearing B16-melanoma.

Immunotherapy with the immunomodulating thymic humoral factor-gamma 2 (THF-gamma 2) octapeptide, combined with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) chemotherapy, will be used for enhancing host immune response to arrest pulmonary metastases of a B16-F10.9 melanoma tumor. In this experimental model of pulmonary metastasis, the highly metastatic B16-F10.9 melanoma tumor cells (2 x 10(5)) were inoculated into the footpad of mice to form a primary tumor. The tumor-bearing leg was surgically removed on reaching the size of 5.5 mm, which resulted in the appearance of metastases in the lungs of the animals. After tumor excision, mice were treated intraperitoneally with a single dose of BCNU (20 or 35 mg/kg) followed by a series of intraperitoneal THF-gamma 2 injections (1 microgram/0.5 ml/injection). Relative to untreated mice and those receiving chemotherapy alone, the antitumor action of the combined THF-gamma 2 chemoimmunotherapy protocol was significantly augmented according to the following in vivo parameters: (a) decreased postsurgical spontaneous metastatic burden; (b) prolonged survival time; (c) increased resistance to tumor cell challenge; and (d) massive infiltration of lymphocytes, polymorphonuclear cells, and macrophages in the lung tissue. The THF-gamma 2 immunotherapy also prevented a decrease in lymphocyte reactivity, otherwise induced by the tumor/BCNU chemotherapy. THF-gamma 2 immunotherapy resulted in restoration of the response to Lipopolysaccharide mitogenic stimulation and the allogeneic response. Our data suggest that postoperative THF-gamma 2 immunotherapy could be a valuable adjunct to anticancer chemotherapy as a treatment for metastatic arrest of melanoma tumor.

Animals↗
PubMed1999

Timed daily administration of prolactin and corticosteroid hormone reduces murine tumor growth and enhances immune reactivity.

In the present study, we investigated the time-dependent interactive effects of daily injections of prolactin (PRL) and corticosterone (CORT) on the activation of lymphocyte function and inhibition of tumor growth in vivo in mice. BALB/c mice were injected subcutaneously with EMT-6 fibrosarcoma cells (a murine connective tissue tumor cell derived from mammary gland), and then different groups of animals were treated with PRL (1 microg/g body weight [BW] ip) at Oh, 4h, 8h, 12h, 16h, or 20h after CRT (1 microg/g BW ip) daily for 10 days. Different control groups were vehicle treated or treated with either hormone alone. Mice were kept in constant light 1 week before and during injections and in a 14:10 light-dark cycle thereafter. Tumor progression was monitored for up to 21 days after the cessation of treatment, and thereafter spleen lymphocytes were harvested and tested for mitogen-triggered proliferation. Prolactin administration at 8h or 16-20h after corticosteroid treatment reduced tumor volume by 77% and 49%, respectively, relative to vehicle-treated controls. Other time relations of hormone treatment were ineffectual. Further studies indicated that the immunosuppressant cyclosporin A (CSA) substantially stimulated tumor growth; this effect was completely abrogated by a simultaneous 8h related hormone treatment. How ever, the 8h hormone treatment was ineffective in inhibiting tumor growth in T-cell-deficient nude mice. Spleen lymphocytes from tumor-bearing (TB) mice showed an elevated basal proliferative capacity stimulated by concanavalin A (ConA; a stimulus for T-cell proliferation) and lipopolysaccharide (LPS; a stimulus for B-cell proliferation) compared to non-TB mice. Spleen lymphocytes from TB mice treated with CORT and PRL at 8h intervals exhibited an increased spontaneous (as well as LPS- and ConA- triggered) proliferation (by 104%, 48%, and 70%, respectively) compared with vehicle control TB mice. Fluorescence-activated cell sorting (FACS) analysis of splenocytes from hormone-treated animals indicated a 34-100% increase in the CD4+ (e.g., T helper cell) population. Treatment of animals with either hormone alone did not inhibit tumor growth or stimulate immune function relative to vehicle controls. The daily rhythms of plasma PRL, CORT, and thyroxine were all substantially altered by the presence of tumor in these mice. These results indicate that appropriately timed daily treatment of PRL and CORT can attenuate tumor growth, in part, via activation of antitumor immune mechanisms. Collectively, these data suggest that circadian neuroendocrine activities must be temporally organized appropriately to inhibit tumor growth.

Animals↗
PubMed1999

Immunopotentiating and immunotherapeutic effects of thymic hormones and factors with special emphasis on thymic humoral factor THF-gamma2.

The essential role played by the thymus in the development of the immune response was well documented in many publications. These findings prompted a long series of studies devised to define the factors produced and secreted by thymus cells, which are involved in the development and nature of immunological responsiveness. First experiments done with crude thymus extracts were followed by isolation of purified products and finally by chemical characterization and synthesis of immunologically active thymus-derived peptides. In this article we review the various thymic hormones and factors described, that is, thymosin fractions 5, the thymosins, prothymosin alpha, thymulin (FTS-Zn), thymopoietin, thymostimulin (TP-1), Thymic humoral factor (THF), and THF-gamma2. Studies demonstrating the activity of the various thymic factors in increasing the immunocompetence potential in both in vitro and in vivo conditions are discussed. The immunostimulatory potential of thymic factors was also investigated in experimental models where beneficial therapeutic effects were sought in a situation of immunological malfunction. The last part of the review is dedicated to clinical trials with thymic factors that revealed improvement in the immunocompetence potential in cases of immunodeficiencies, viral infections, and cancer and its correlation with therapeutic effectiveness. It seems that more research is required in order to better define conditions for the use of thymic factors in immunotherapy.

Animals↗
PubMed1998

Role of chronic inflammation in the promotion of prostatic hyperplasia in rats.

PURPOSE: Chronic prostatitis is a common histopathological finding in prostatectomized patients. A possible interrelationship between the presence of leukocyte exudate and the extent of the hyperplastic lesions has been suggested. The aim of the present study was to analyze the effect of the immunomodulator compounds, Complete Freund Adjuvant (CFA) and cyclosporin A (CsA), administered alone or together with citral on the induction and extent of rat prostatic hyperplasia. MATERIALS AND METHODS: Adolescent Wistar rats (42 days old) were given citral alone or combined with CFA or CsA for one month. Semiquantitative analysis of the extent of the hyperplastic lesions was made with the histoscore protocol. RESULTS: CsA did not induce hyperplastic changes or abolish the ability of citral to promote hyperplastic changes or to affect the extent of the lymphocytic exudate in the stroma. CFA itself, however, had a proliferative action on the prostatic epithelium, and it augmented the hyperplastic changes induced by citral and even induced atypical transformations of the acinar epithelium. CONCLUSIONS: Immunoinflammatory stimulators might play a role in the prostatic epithelial cell growth and proliferation processes, most probably by modulation of the cytokine system.

Acyclic Monoterpenes↗
PubMed1997

Characterization and quantitative analysis of serum IgG class and subclass response to Shigella sonnei and Shigella flexneri 2a lipopolysaccharide following natural Shigella infection.

The IgG subclass response to Shigella sonnei and Shigella flexneri 2a lipopolysaccharide (LPS) was examined in subjects naturally exposed to these organisms. Affinity-purified LPS antibodies obtained using a column of Shigella LPS bound to epoxy-activated Sepharose 6B were used as standards to calibrate the serum antibody response to natural Shigella infection. The geometric mean concentrations of specific IgG in sera from those not exposed to Shigella organisms were 7.9 microg/mL against S. sonnei LPS and 18.6 microg/mL against S. flexneri 2a LPS. After natural exposure to S. sonnei or S. flexneri 2a, the concentrations rose to 30.3 and 127.9 microg/mL, respectively. IgG2 was the major component in the anti-S. flexneri subclass response, while the anti-S. sonnei response was dominated by IgG1. High levels of IgG1 antibodies before exposure to organisms from either Shigella serogroup correlated with a lower risk of developing symptomatic infection.

Adolescent↗
PubMed1997

SP-A enhances phagocytosis of Klebsiella by interaction with capsular polysaccharides and alveolar macrophages.

We found that surfactant protein A (SP-A) enhances phagocytosis of Klebsiella pneumoniae K21a but not of K2 serotypes by alveolar macrophages. SP-A interacted with the capsule of K21a (containing Man alpha1 Man sequences) as shown by SP-A-induced agglutination of the bacteria, by binding of SP-A-coated particles onto the bacterial surface, and by binding of SP-A to immobilized parent K21a strain and recombinant strains that switched their capsule from K2 to K21a. In contrast, only marginal binding of SP-A to K2 parent strain (lacking this sequence) could be detected. Furthermore, binding of capsular polysaccharide of K21a to immobilized SP-A was inhibited by mannan but not by lipopolysaccharide and K2 capsular polysaccharide. SP-A-treated macrophages bound increased numbers of parent K21a strain and recombinant strains of K21a capsule type but considerably less parent K2 strain. SP-A also enhanced killing of K21a strains by macrophages. The enhanced binding of K21a by macrophages pretreated with SP-A was inhibited by mannan, suggesting that binding is mediated by the mannose receptor on macrophages. We conclude that SP-A increases phagocytosis of the Klebsiella by two mechanisms, one of which is by serving as an opsonin, which binds to the capsular polysaccharides of the bacteria and potentially to SP-A receptors on the macrophages, and the other by activating the macrophages, resulting in increased activity of the mannose receptor.

Animals↗
PubMed1997

Phagocyte-bacteria interactions.

Recognition and phagocytosis of micro-organisms in a serum-poor environment represent innate immunity against many extracellular pathogens. As a paradigm for such processes, we discuss the recognition of Klebsiella pneumoniae by alveolar macrophages and monocyte-derived macrophages in the absence of serum. Macrophages recognize and subsequently kill Klebsiella expressing Man-alpha 2/3-Man or Rha-alpha 2/3-Rha sequences in their capsular polysaccharides by two mechanisms: (a) recognition of the capsular structures by macrophage mannose receptors, and (b) opsonization by the lung surfactant protein A (SP-A), which binds to the capsular polysaccharides of Klebsiella and to SP-A receptors on the macrophages. Sp-A may also enhance phagocytosis by increasing the activity of macrophage mannose receptors. We conclude that a specific microbial surface structure may be a target for recognition by macrophages via several mechanisms, as exemplified in the case of Klebsiella capsular polysaccharides. Multiple recognition mechanisms of pathogens by macrophages may be essential to provide innate immunity to reduce the frequency of infections caused by a relatively less virulent bacterium in the immuno-compromised host.

Animals↗
PubMed1996

Inhibition of murine Lewis lung carcinoma metastases by combined chemotherapy and intranasal THF-gamma 2 immunotherapy.

Previous research in our laboratories has shown that the immunoregulatory octapeptide, THF-gamma 2, potentiates the efficacy of anticancer chemotherapy in experimental animal models of local plasmacytoma and repairs drug-induced defects in immunocompetence. The highly metastatic, murine D122 lung carcinoma model has been shown to be useful for evaluating the efficacy of experimental antimetastatic therapeutic modalities. The goal of the present study was to determine whether intranasal thymic humoral factor-gamma 2 (THF-gamma 2) immunotherapy, after a single dose of chemotherapy, could inhibit the development of lung metastases, restore immunocompetence, and increase survival in syngeneic C57BL/6 mice bearing highly metastatic Lewis lung carcinoma (D122) solid footpad tumors. Relative to untreated mice and those receiving chemotherapy alone, mice receiving combined chemoimmunotherapy showed the following significant differences: (a) decreased lung metastatic load as assessed by lung weight, (b) prolonged survival time, (c) massive infiltration of lymphoid cells in the lungs, and (d) restoration of impaired immune parameters to normal values in melphalan-treated mice. THF-gamma 2 prevented tumor emboli from colonizing the target tissue, probably by inducing expansion of the lymphoid cell compartment. When used as an adjunct to anticancer chemotherapy, intranasal THF-gamma 2 immunotherapy is a simple and safe treatment modality that seems to be promising for inhibiting lung metastases.

Adjuvants, Immunologic↗
PubMed1996

Thymic humoral factor-gamma 2 (THF-gamma 2) immunotherapy reduces the metastatic load and restores immunocompetence in 3LL tumor-bearing mice receiving anticancer chemotherapy.

In mice bearing immunogenic tumors, adding thymic humoral factor-gamma 2 (THF-gamma 2)1 immunotherapy as an adjunct to anticancer chemotherapeutic regimens not only potentiates the antitumor activity of each drug but also repairs tumor/chemotherapy-induced damage to T-cell populations and functions. The Lewis lung carcinoma (3LL) is a weakly immunogenic, highly metastatic tumor in C57BL/6 mice. To investigate whether the immunoregulatory octapeptide is also effective against a tumor that does not elicit an antitumor immune response, we assessed the effect of combination THF-gamma 2 immunotherapy and chemotherapy in 3LL-bearing mice. The results indicate that THF-gamma 2 combined with either Melphalan or 5-Fluorouracil was more effective in reducing metastatic load than either chemotherapeutic drug alone and was characterized by massive infiltration of lymphatic cells. The combined chemoimmunotherapy treatment also prolonged the survival time in all treated animals and repaired T-cell defects and impaired in vitro cellular immune response parameters, induced either by the tumor or by chemotherapy. THF-gamma 2 immunotherapy reversed the decrease in the number of bone-marrow myeloid colonies (GM-CFU) induced by chemotherapy treatment of tumor-bearing mice, supporting the hypothesis that THF-gamma 2 directly stimulates the proliferation of myeloid stem cells. The overall results imply, that when administered as an adjunct to chemotherapy, THF-gamma 2 immunotherapy is equally effective against immunogenic and nonimmunogenic tumors.

Animals↗