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Biomedical subjects

J H Qian

Publications and source records attributed to J H Qian.

18 recordsLinked to original sources
PubMed1992

Targeting of anti-tumor responses with bispecific antibodies.

T cells can be induced to specifically lyse tumor cells with bispecific antibodies containing anti-T cell receptor mAbs crosslinked to anti-tumor mAbs. Such "targeted cytolysis" requires that the target cell be bound directly to the cytotoxic cell. In addition, targeted T cells mediate a second activity, the secretion of factors that can block the growth of both tumor target cells and bystander tumor cells. When given to nude mice bearing intraperitoneal human ovarian carcinoma, targeted human T cells cause the rapid removal of most tumor cells from the peritoneum, and markedly prolong the times of survival of treated mice. The efficacy of targeted T cells for treating human cancer is currently being tested in clinical trials.

Animals↗
PubMed1992

Targeted cytokine production.

It has been well established that bispecific antibodies containing anti-T-cell receptor MAbs crosslinked to anti-tumor MAbs induce T cells to lyse tumor cells, as measured in a 51Cr-release assay. Such lysis requires direct attachment between target and cytotoxic cells and most probably involves the exocytosis of cytolytic substances into the cell:cell interface. In addition, targeted T cells mediate a second activity, the secretion into the medium of factors that can block the growth of bound tumor cells and unbound bystander cells. In order to test how targeted effector cells mediate anti-tumor effects in vivo, we are currently developing a totally syngeneic murine system in which murine T cells are targeted against mouse mammary tumors. The system allows us to treat both primary tumors and tumor transplants, using a mammary-tumor-virus antigen as the entity that is specifically recognized on the tumor cells.

Animals↗
PubMed1991

Human peripheral blood lymphocytes targeted with bispecific antibodies release cytokines that are essential for inhibiting tumor growth.

We have compared the mechanisms by which human PBL targeted with bispecific antibodies either lyse tumor cells or block their growth in culture or in mice. We found that resting PBL were unable to mediate lysis, but were able to block tumor growth. Moreover, targeted PBL were unable to lyse bystander cells, whereas targeted PBL did block the growth of bystander tumor cells in culture and in nude mice. Supernatants from cultures of targeted PBL, or from PBL grown on anti-CD3-coated flasks, blocked the growth of tumor cells in the absence of added effector cells, and antibodies against TNF-alpha and IFN-gamma reversed the inhibition of tumor growth, but had no effect upon cytolysis mediated by targeted by PBL. Our results show that targeted human PBL mediate two different antitumor activities: lysis, which occurs rapidly and requires the direct attachment of the target cell to the cytotoxic cell, and tumor growth inhibition, which is mediated by cytokines released into the medium as a result of receptor cross-linking. The inhibition of bystander tumor growth in mice by targeted PBL suggests that factor release is sufficient to block tumor growth in vivo. Targeted factor release therefore provides a mechanism by which targeted PBL could block the growth of tumor cells in vivo that were not bound by the effector cells, but which were located in the vicinity of tumor cells that were bound.

Animals↗
PubMed1991

An ERP-based, control-question lie detector analog: algorithms for discriminating effects within individuals' average waveforms.

Two experimental, P3-based analog control question tests were run. In both, guilty subjects were presented with a set of seven phrases describing antisocial acts of which they were innocent, plus one phrase describing a guilty act (the analog relevant question), and one act to which a "yes" response (yes-target stimulus) was required to assure attention. Innocent subjects (run only in Experiment 1) saw all innocent acts plus the yes-target act. Thus nine acts were seen by guilty and innocent subjects. In both experiments, all subjects had to selectively review their guilty acts privately. Also in both experiments, all subjects were especially questioned about four acts of which guilty subjects were known to be innocent of all but one, and of which innocent subjects were known to be innocent of all. (These falsely accused acts were regarded as control question analogs.) In Experiment 1, the private review and rehearsal took place on the same day as the main test. In Experiment 2, one subgroup (delay-only) of guilty subjects was run as in Experiment 1, except that the private review-rehearsal was separated from the main run by 7-14 days. Another subgroup (delay-rehearsal) of guilty subjects was run just as was the subgroup delay-only, except that the delay-rehearsal subgroup additionally received a non-selective additional interrogation/rehearsal on the delayed main run day. Parietally maximal P3 responses were obtained to yes-target items in all groups. In Experiment 1, only in the guilty group was the relevant-minus-control P3 amplitude difference significant. In Experiment 2, the difference was significant only in the delay-rehearsal subgroup. A four-step algorithm (involving relevant-control amplitude differences and relevant target vs. control-target cross-correlations) was used to assess effects within individuals. In Experiment 1, 12 of 13 guilty subjects and 13 of 15 innocent subjects were correctly diagnosed. In Experiment 2, 3 of 8 delay-only subjects and 7 of 8 delay-rehearsal subjects were correctly diagnosed. In Experiment 2, the relevant-minus-control group P3 amplitude difference was significant in the delay-rehearsal but not in the delay-only subgroup. The results suggest that temporally proximal, non-selective rehearsal procedures are sufficient to activate personal knowledge of a salient (oddball), P3-generating stimulus phrase, and that even selective rehearsal of guilty acts is not sufficient without temporal proximity.

Adolescent↗
PubMed1988

Studies on the induction of tolerance to alloantigens. III. Induction of antibodies directed against alloantigen-specific delayed-type hypersensitivity T cells by a single injection of allogeneic lymphocytes via portal venous route.

BALB/c mice were inoculated with normal C3H/He spleen cells via the portal venous (p.v.) route. Intravenous injection of serum from these BALB/c mice into naive syngeneic mice resulted in almost complete abrogation of their ability to generate anti-C3H/He delayed-type hypersensitivity (DTH) responses as induced by s.c. immunization with C3H/He cells. Since a portion of the same serum did not inhibit the development of anti-C57BL/6 DTH responses, the suppressive effect of the transferred serum was alloantigen-specific. Such serum factor(s) was produced in normal but not in nude mice and the suppressive activity was transferred in H-2- or immunoglobulin allotype-incompatible combinations. Immunochemical analyses of this serum suppressive factor have revealed that its m.w. was approximately 150,000, corresponding to the size of immunoglobulin (Ig)G, and that the activity was trapped by protein A or by an anti-immunoglobulin column. Although the absorption of the serum from anti-C3H/He-tolerant BALB/c mice with C3H/He target spleen cells did not abrogate the suppressive activity, the additional absorption with spleen cells from anti-C3H/He hyperimmune BALB/c mice almost completely eliminated the suppressive potential. Moreover, pretreatment of BALB/c anti-C3H/He DTH effector spleen cells with the above serum from tolerant mice induced the inhibition of anti-C3H/He DTH responses. Taken together, these results indicate that a single injection of allogeneic cells via the p.v. route results in the production of antibody capable of inhibiting the capacity of DTH effector cells specific for alloantigens used for the p.v. presensitization.

Animals↗
PubMed1988

Tolerance induction of alloreactivity by portal venous inoculation with allogeneic cells followed by the injection of cyclophosphamide. II. Cellular and molecular mechanisms underlying tolerance.

BALB/c mice receiving allogeneic C3H/He or C57BL/6 spleen cells via portal venous (p.v.) route or a single administration of cyclophosphamide (Cy) were capable of rejecting the respective allogeneic C3H/He- or C57BL/6-derived tumor cells. In contrast, the combined treatment of p.v. inoculation with allogeneic lymphocytes and Cy administration abrogated the capability of rejecting allogeneic tumor cells. Such abrogation of alloreactivity was alloantigen-specific and associated with the suppression of potentials to generate delayed-type hypersensitivity (DTH) and cytotoxic T lymphocyte (CTL) responses to alloantigens. This was further substantiated by the inhibition of molecular mechanisms underlying anti-allo-DTH and -CTL responses. Thus, the above combined treatment led to the decreased production of lymphokines such as macrophage-activating factor (MAF) and interleukin 2 (IL2) following the stimulation with the relevant alloantigens. These results demonstrate that p.v. inoculation of allogeneic cells followed by a single administration of Cy results in the effective elimination of alloreactivity as verified by the suppression of cellular and molecular mechanisms of alloreactive responses.

Animals↗
PubMed1988

Targeting of cytotoxic cells against tumors with heterocrosslinked, bispecific antibodies.

Cytotoxic cells express specific receptors on their surfaces by which they distinguish altered or foreign cells from normal autologous cells. Recently, a method has been developed by which the natural recognition system of cytotoxic cells can be artificially manipulated, giving rise to cytotoxic cells of any desired specificity, including specificity against tumor and virally infected cells. The method for retargeting cytotoxic cells employs heterocrosslinked antibodies, in which one antibody is directed against the cytotoxic cell receptor (CCR) involved in lysis, while the second antibody is directed against a target cell structure, for example a tumor or viral antigen. By linking the CCR directly to the target cell, the heterocrosslinked antibodies promote the formation of effector: target conjugates and signal the cytotoxic cell to deliver a lethal hit. T cells can be targeted by heteroconjugates containing antibodies against components of the T cell receptor complex, e.g., Ti or CD3, while several types of antibody-dependent cellular cytotoxicity (ADCC) effector cells, including K/NK cells, macrophages, and neutrophils, are targeted using heteroconjugates containing antibodies against Fc gamma receptors. In peripheral blood from normal donors at least six types of targetable activities have been identified in vitro. In Winn type tumor neutralization assays in nude mice, targeted T and K cells can prevent the establishment of subcutaneous tumor at low effector: tumor ratios. Moreover, targeted human peripheral blood T cells cause the eradication of established intraperitoneal human ovarian carcinoma in nude mouse models. Targeted cytotoxic cells therefore hold great promise as a novel form of cancer immunotherapy in humans.

Animals↗
PubMed1987

Abrogation of the capacity of delayed-type hypersensitivity responses to alloantigens by intravenous injection of neuraminidase-treated allogeneic cells.

BALB/c or C3H/He mice were inoculated i.v. with allogeneic spleen cells untreated or treated with neuraminidase. Appreciable or potent anti-allo-delayed-type hypersensitivity (DTH) responses were observed when mice were inoculated i.v. with untreated allogeneic cells or inoculated i.v. with those cells followed by s.c. immunization with untreated allogeneic cells. In contrast, i.v. inoculation of neuraminidase-treated allogeneic cells (presensitization) not only failed to induce any significant anti-allo-DTH responses but also abolished the capability of the animals to develop DTH responses after s.c. immunization, indicating the tolerance induction. This tolerance was alloantigen-specific, and rapidly inducible and long lasting. The induction of suppressor cell activity was demonstrated in tolerant mice. However, this activity was associated only with the tolerant state around 4 to 7 days after the i.v. presensitization, but was no longer detected in mice more than 14 days after the presensitization, although these mice exhibited complete tolerant state. When spleen cells from such tolerant mice were transferred i.v. into 600 R x-irradiated syngeneic recipient mice alone or together with normal syngeneic spleen cells, these tolerant spleen cells themselves failed to induce DTH responses but did not exhibit suppressive effect on the generation of DTH responses induced by normal spleen cells co-transferred. These results indicate that i.v. administration of neuraminidase-treated allogeneic cells results in the induction of alloantigen-specific tolerance which is not always associated with the induction of suppressor cell activity but rather with the elimination or functional impairment of alloantigen-specific clones.

Animals↗
PubMed1987

Tolerance induction of alloreactivity by portal venous inoculation with allogeneic cells followed by the injection of cyclophosphamide. I. Specific suppression of alloreactive cytotoxic and delayed-type hypersensitivity responses as well as allograft rejection.

BALB/c mice receiving allogeneic C3H/He spleen cells via portal venous (p.v.) route or a single administration of cyclophosphamide (Cy) were capable of rejecting allogeneic X5563 tumor cells (C3H/He origin). In contrast, the combined treatment of p.v. inoculation with C3H/He cells and Cy administration abrogated the capability of rejecting allogeneic X5563 tumor cells. The dose of Cy and interval between p.v. presensitization and Cy injection needed to be more than 1.5 mg Cy/mouse and less than 2 days, respectively. Such abrogation of alloreactivity was alloantigen-specific, since p.v. inoculation of C3H/He cells followed by Cy injection resulted in selective inhibition of rejecting allogeneic C3H/He tumor cells (X5563 plasmacytoma) without suppressing the capability of rejecting allogeneic C57BL/6 tumor cells (EL4 leukemia). Most important, the induction of alloantigen-specific unreactivity by p.v. presensitization plus Cy injection contrasted with the failure of intravenous or subcutaneous presensitization plus Cy injection to induce tolerance that permits the growth of allogeneic tumor cells inoculated. This was substantiated by the finding that p.v. presensitization with C3H/He cells prior to Cy injection eliminated anti-C3H/He cytotoxic T lymphocyte (CTL) and delayed-type hypersensitivity (DTH) potentials under conditions in which appreciable CTL and DTH responses are induced in mice inoculated via the i.v. route before Cy injection. These results demonstrate that p.v. inoculation of allogeneic cells followed by a single administration of Cy results in more efficient elimination of antialloantigen CTL and DTH reactivities, leading to the abrogation of potential to reject the allogenic tumor graft.

Animals↗
PubMed1987

Immunogenetic analysis of tolerance induction in anti-alloantigen delayed type hypersensitivity responses by portal venous pre-inoculation with allogeneic cells.

The present study investigates some of the immunogenetic bases for tolerance of anti-allo-delayed type hypersensitivity (DTH) responses as induced by pre-inoculating allogeneic cells via portal venous (p.v.) route. BALB/c mice were injected with totally allogeneic C57BL/6 or H-2 incompatible BALB.B spleen cells via p.v. route. These mice not only failed to exhibit anti-H-2b DTH responses, but also abrogated the potential to generate H-2b-specific DTH responses as induced by the subsequent immunization with H-2b spleen cells via subcutaneous (s.c.) route. The p.v. presensitization with allogeneic spleen cells differing at either class I or class II of major histocompatibility complex (MHC) resulted in the tolerance induction of DTH responses to the respective allogeneic class I or class II MHC antigens. Moreover, the p.v. administration of the class I-positive allogeneic cell fraction depleted of class II-positive component into recipients differing at both class I and class II was capable of inducing anti-class I DTH tolerance. These results indicate that anti-allo-class I or class II DTH tolerance can be induced independently and that the existence of class II antigens on p.v.-presensitized cells is not necessarily required for the tolerance induction of anti-allo-class I DTH response.

Animals↗
PubMed1987

Suppressive effect of portal venous inoculation with tumor cells on the anti-tumor immune potential.

The effect of portal venous (pv) administration of syngeneic tumor cells on the potential to generate anti-tumor immune resistance was examined. C3H/He mice were inoculated with syngeneic X5563 tumor cells via the pv or intravenous (iv) route. A single pv administration of 10,000 R X-irradiated X5563 cells into C3H/He mice not only failed to induce anti-X5563 immunity but also abolished the capability of the mice to develop anti-X5563 in vitro cytotoxic and in vivo protective immunity as induced by intradermal (id) inoculation of viable X5563 cells followed by the surgical resection of the tumor (immunization procedure). Such immunosuppression was also obtained by pv inoculation of tumor cells after the above immunization procedure. The immunosuppression induced by the pv injection of tumor cells before or after the immunization procedure was tumor-specific, since the pv sensitizing regimen using X5563 tumor cells did not interfere with the generation of immunity against another syngeneic tumor, MH134. More importantly, the pv route-induced suppression contrasted with the lack of inhibiting effect of iv inoculation with tumor cells on the induction of the tumor immunity. These results indicate that the host's tumor-specific immune capability is markedly suppressed in an anti-tumor sensitizing stage-independent manner when tumor cells enter the pv circulation.

Animals↗
PubMed1986

Studies on the induction of tolerance to alloantigens. II. The generation of serum factor(s) able to transfer alloantigen-specific tolerance for delayed-type hypersensitivity by portal venous inoculation with allogeneic cells.

The administration of C3H/He spleen cells into allogeneic BALB/c mice via portal venous (p.v.) route resulted in C3H/He alloantigen-specific tolerance for delayed-type hypersensitivity (DTH) responses. When serum from these tolerant BALB/c mice were transferred into naive syngeneic BALB/c mice, the recipient mice lost the capability of generating DTH responses as induced by s.c. immunization with C3H/He cells. Tolerance was transferred only by serum from BALB/c mice inoculated p.v. with C3H/He cells, but not by serum from C3H/He mice inoculated p.v. with C3H/He cells, or BALB/c mice inoculated i.v. with C3H/He cells. This tolerogenic activity in serum from p.v. inoculated BALB/c mice was C3H/He alloantigen specific, because the transfer of the serum did not interfere with the development of anti-C57BL/6 DTH responses in recipient BALB/c mice. Such a serum factor(s) was inducible as early as 1 wk after the inoculation of C3H/He cells into BALB/c mice and not associated with anti-C3H/He alloantibody activity. Moreover, anti-C3H/He or C57BL/6-specific tolerogenic factor(s) prepared in the respective BALB/c or C3H/He mice was successfully transferred into totally allogeneic recipient mice, indicating no requirement of H-2, as well as non-H-2 restriction for the function of serum tolerogenic factor(s). Thus this study demonstrates that p.v. inoculation of allogeneic cells generates serum factor(s) able to transfer in H-2 and non-H-2-unrestricted manners the in vivo tolerance of the alloreactivity specific for alloantigens used for p.v. inoculation.

Animals↗
PubMed1986

Suppressive effect of ultraviolet-B-irradiation of epidermal cells on the induction of contact sensitivity.

Contact sensitivity to trinitrophenyl (TNP) hapten was induced by subcutaneous (s.c.) administration of TNP-modified syngeneic spleen cells or epidermal cells (EC) (TNP-EC). Intraperitoneal (i.p.) inoculation of TNP-EC resulted in a comparable response, whereas i.p. administration of TNP-spleen cells or TNP-modified-ultraviolet (UV)-preirradiated EC (TNP-UV-EC) failed to induce TNP-contact sensitivity responses. The present study investigates the effect of UV-irradiation on the potential of EC for inducing the contact sensitivity response. Exposure of BALB/c mouse EC in vitro to 1600 J/m2 of UV-B before they were modified with TNP had no discernible effect on the Ia-positivity and viability of EC. Coexistence of TNP-UV-EC had no inhibitory effect upon the contact sensitivity response induced by TNP-EC via the i.p. route. The absence of suppressor cell generation was substantiated by the adoptive transfer of spleen cells from mice administered TNP-UV-EC i.p. to normal syngeneic mice. The effect of interleukin 1 (IL-1) or epidermal cell-derived thymocyte-activating factor (ETAF) in restoring the ability of TNP-UV-EC to induce contact sensitivity was examined. IL-1 or ETAF administered along with TNP-spleen cells i.p. induced a potent contact sensitivity response, whereas the same preparations of IL-1 or ETAF were unable to restore the contact sensitivity induction by TNP-UV-EC. The results are discussed in the context of UV-induced cell surface changes of the Langerhans cell population.

Animals↗
PubMed1985

Prevention of tumor metastasis after surgical removal of primary tumor by using in vitro activated macrophages.

In vitro activation of peritoneal macrophages by Propionibacterium acnes and its immunotherapeutic potential for inhibiting metastasis was investigated. C3H/HeN mouse adherent peritoneal exudate cells as a source of macrophages were treated in vitro with P. acnes. These P. acnes-activated macrophages were tested for tumoricidal activity in vitro and antimetastatic activity in vivo. In vitro cytotoxicity tests revealed that they had potent cytotoxicity. Surgical resection of X5563 tumors in syngeneic C3H/HeN mice 10 days after the tumor implantation failed to rescue the hosts from tumor metastasis despite successful removal of the primary tumor. When the activated macrophages were transferred intravenously into C3H/HeN mice following the surgical operation, an appreciable number of mice survived without exhibiting any sign of metastasis. Thus, these results demonstrate that macrophages can be activated in vitro by utilizing appropriate stimulating reagents, and that these activated macrophages have a potent antimetastatic effect.

Animals↗
PubMedDate not supplied

Removal and distribution of iron, manganese, cobalt, and nickel within a Pennsylvania constructed wetland treating coal combustion by-product leachate.

A flow-through wetland treatment system was constructed to treat coal combustion by-product leachate from an electrical power station at Springdale, Pennsylvania. In a nine-compartment treatment system, four cattail (Typha latifolia L.) wetland cells (designated Cells 1 through 4) successfully removed iron (Fe) and manganese (Mn) from the inlet water; Fe and Mn concentrations were decreased by an average of 91% in the first year (May 1996-May 1997), and by 94 and 98% in the second year (July 1997-June 1998), respectively. Cobalt (Co) and nickel (Ni) were decreased by an average of 39 and 47% in the first year, and 98 and 63% in the second year, respectively. Most of the metal removed by the wetland cells was accumulated in sediments, which constituted the largest sink. Except for Fe, metal concentrations in the sediments tended to be greater in the top 5 cm of sediment than in the 5- to 10- or 10- to 15-cm layers, and in Cell 1 than in Cells 2, 3, and 4. Plants constituted a much smaller sink for metals; only 0.91, 4.18, 0.19, and 0.38% of the Fe, Mn, Co, and Ni were accumulated annually in the aboveground tissues of cattail, respectively. A greater proportion of each metal (except Mn) was accumulated in cattail fallen litter and submerged Chara (a macroalga) tissues, that is, 2.81, 2.75, and 1.05% for Fe, Co, and Ni, respectively. Considerably higher concentrations of metals were associated with cattail roots than shoots, although Mn was a notable exception.

Biological Availability↗
PubMedDate not supplied

Trace element removal from coal ash leachate by a 10-year-old constructed wetland.

This study investigated the ability of a 10-yr-old constructed wetland to treat metal-contaminated leachate emanating from a coal ash pile at the Widows Creek electric utility, Alabama (USA). The two vegetated cells, which were dominated by cattail (Typha latifolia L.) and soft rush (Juncus effusus L.), were very effective at removing Fe and Cd from the wastewater, but less efficient for Zn, S, B, and Mn. The concentrations were decreased by up to 99% for Fe, 91% for Cd, 63% for Zn, 61% for S, 58% for Mn, and 50% for B. Higher pH levels (>6) in standing water substantially improved the removing efficiency of the wetland for Mn only. The belowground tissues of both cattail and soft rush had high concentrations of all elements; only for Mn, however, did the concentration in the shoots exceed those in the belowground tissues. The concentrations of trace elements in fallen litter were higher than in the living shoots, but lower than in the belowground tissues. The trace element accumulation in the plants accounted for less than 2.5% of the annual loading of each trace element into the wetland. The sediments were the primary sinks for the elements removed from the wastewater. Except for Mn, the concentrations of trace elements in the upper layer (0-5 cm) of the sediment profile tended to be higher than the lower layers (5-10 and 10-15 cm). We conclude that constructed wetlands are still able to efficiently remove metals in the long term (i.e.,>10 yr after construction).

Biological Availability↗