bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting Rat Brainstem Glioma Using Human Neural Stem Cells and Human Mesenchymal Stem Cells
Authors: Lee Do-Hun , Ahn Yong , Kim Seung U. , Wang Kyu-Chang , Cho Byung-Kyu , Phi Ji Hoon , Park In Ho , Black Peter M. , Carroll Rona S. , Lee Joonyub , Kim Seung-Ki
Published: July 2009

Purpose: Brainstem gliomas are usually inoperable and have a dismal prognosis. Based on the robust tropisms of neural stem cells (NSC) and mesenchymal stem cells (MSC) to brain tumors, we compared the tumor-tropic migratory capacities of these stem cells and evaluated the therapeutic potential of genetically engineered human NSCs encoding cytosine deaminase (CD) and IFNβ against brainstem gliomas.

Experimental Design: The directed migratory capacities of NSCs and MSCs to brainstem glioma (F98) were evaluated both in vitro and in vivo. The human NSCs (HB1.F3) and various human MSCs, such as bone marrow–derived MSCs (HM3.B10), adipose tissue–derived MSCs, and umbilical cord blood–derived MSCs, were tested. Human fibroblast cells (HFF-1) were used as the negative control. As a proof of concept, the bioactivity of HB1.F3-CD-IFNβ was analyzed with a cell viability assay, and animals with brainstem gliomas were injected with HB1.F3-CD-IFNβ cells followed by systemic 5-fluorocytosine treatment.

Results: In an in vitro modified Transwell migration assay and in vivo stem cell injection into established brainstem gliomas in rats, all the stem cells showed a significant migratory capacity compared with that of the control (P < 0.01). Histologic analysis showed a 59% reduction in tumor volume in the HB1.F3-CD-IFNβ–treated group (P < 0.05). Apoptotic cells were increased 2.33-fold in animals treated with HB1.F3-CD-IFNβ compared with the respective control groups (P < 0.01).

Conclusion: The brainstem glioma-tropic migratory capacities of MSCs from various sources were similar to those of NSCs. Genetically engineered NSCs show therapeutic efficacy against brainstem gliomas.
The Green Tea Polyphenol EGCG Potentiates the Antiproliferative Activity of c-Met and Epidermal Growth Factor Receptor Inhibitors in Non–small Cell Lung Cancer Cells
Authors: Milligan Shawn A. , Burke Patrick , Coleman David T. , Bigelow Rebecca L. , Steffan Joshua J. , Carroll Jennifer L. , Williams Briana Jill , Cardelli James A.
Published: July 2009

Purpose: Activation of the c-Met and epidermal growth factor receptors (EGFR) promotes the growth and survival of non–small cell lung cancer (NSCLC). Specific receptor antagonists have shown efficacy in the clinic, but tumors often become resistant to these therapies. We investigated the ability of (-)-epigallocatechin-3-gallate (EGCG) to inhibit cell proliferation, and c-Met receptor and EGFR kinase activation in several NSCLC cell lines.

Experimental Design: NSCLC cell lines with variable sensitivity to the EGFR antagonist erlotinib were studied. Cell growth was evaluated using proliferation and colony formation assays. Kinase activation was assessed via Western blot analysis. Experiments were conducted with EGCG, the EGFR antagonist erlotinib, and the c-Met inhibitor SU11274. The antagonists were also tested in a xenograft model using SCID mice.

Results: EGCG inhibited cell proliferation in erlotinib-sensitive and -resistant cell lines, including those with c-Met overexpression, and acquired resistance to erlotinib. The combination of erlotinib and EGCG resulted in greater inhibition of cell proliferation and colony formation than either agent alone. EGCG also completely inhibited ligand-induced c-Met phosphorylation and partially inhibited EGFR phosphorylation. The triple combination of EGCG/erlotinib/SU11274 resulted in a greater inhibition of proliferation than EGCG with erlotinib. Finally, the combination of EGCG and erlotinib significantly slowed the growth rate of H460 xenografts.

Conclusion: EGCG is a potent inhibitor of cell proliferation, independent of EGFR inhibition, in several NSCLC cell lines, including those resistant to both EGFR kinase inhibitors and those overexpressing c-Met. Therefore, EGCG might be a useful agent to study as an adjunct to other anticancer agents.
Tumor Endothelial Cells Join the Resistance
Authors: Dudley Andrew C. , Klagsbrun Michael
Published: July 2009

The field of antiangiogenesis research has been met with some surprises, including the realization that tumor blood vessels are more complex and labile than expected. In this issue of Clinical Cancer Research, Xiong and colleagues show that tumor-specific endothelial cells are less sensitive to cytotoxic and antiangiogenic drugs compared to their normal counterparts.
Persuading Natural Killer Cells to Eliminate Bad B Cells
Authors: Cooper Laurence J.N.
Published: July 2009

Clinical trials are underway infusing T cells genetically modified to be specific for B-cell malignancies using a chimeric antigen receptor (CAR) to redirect specificity for CD19. However, issues remain about whether the CAR can provide a fully competent application signal and whether other lymphocytes with lytic capacity can target CD19+ tumors.
A novel agonistic antibody to human death receptor 4 induces apoptotic cell death in various tumor cells without cytotoxicity in hepatocytes
Authors: Sung Eun-Sil , Park Kyung-Jin , Lee Seung-Hyun , Jang Yoon-Seon , Park Sang-Koo , Park Yoo-Hoi , Kwag Won-Jae , Kwon Myung-Hee , Kim Yong-Sung
Published: July 2009

The proapoptotic tumor necrosis factor–related apoptosis inducing ligand (TRAIL) receptors death receptor (DR) 4 and DR5 are attractive targets to develop the receptor-specific agonistic monoclonal antibodies (mAb) as anticancer agents because of their tumor-selective cell death–inducing activity. Here, we report a novel agonistic mAb, AY4, raised against human DR4 in mice. ELISA analysis revealed that AY4 specifically bound to DR4 without competition with TRAIL for the binding. Despite distinct binding regions of AY4 on DR4 from those of TRAIL, AY4 as a single agent induced caspase-dependent apoptotic cell death of several tumor types through the extrinsic and/or intrinsic pathways without substantial cytotoxicity to normal human hepatocytes. Further, the AY4-sensitive cells followed the same cell death characteristics classified as type I and type II cells by the response to TRAIL, suggesting that the cell death profiles in responses to DR4 and/or DR5 stimulation are determined by the downstream signaling of the receptor rather than the kind of receptor. Noticeably, AY4 efficiently induced cell death of Jurkat cells, which have been reported to be resistant to other anti-DR4 agonistic mAbs, most likely due to the unique epitope property of AY4. In vivo administration of AY4 significantly inhibited tumor growth of human non–small cell lung carcinoma preestablished in athymic nude mice. Conclusively, our results provide further insight into the DR4-mediated cell death signaling and potential use of AY4 mAb as an anticancer therapeutic agent, particularly for DR4-responsive tumor types. [Mol Cancer Ther 2009;8(8):2276–85]
Role of GABAB Receptor Agonist Baclofen in Acute Pain Modulation during the Early Postnatal Period
Authors: Franek Miloslav , Vaculin Simon
Published: July 2009

Background: Baclofen, a specific GABAB receptor agonist, is used to treat spasticity and its off-label use includes the treatment of pain. The aim of this study was to show the role of baclofen in acute pain modulation during the early postnatal period. Methods: Baclofen was tested in 2 doses (1 and 5 mg/kg) in 3 age groups (postnatal days 7, 16 and 21) in order to assess its effect on acute nociception and motor co ordination in rat pups. Pain was evaluated by measurement of paw/tail withdrawal latencies, and motor coordination by age-relevant tests. Results: Although baclofen impaired motor function in all age groups, no changes in paw withdrawal latencies were observed. On the other hand, baclofen significantly increased tail withdrawal latencies of all groups. Conclusion: It is concluded that the GABAB system is functionally matured in the early postnatal period and plays a similar, but not the same, role as in adulthood.
In vitro Studies of Chicken Lymphoid Cells
Authors: Alm G.V.
Published: July 2009

White leghorn chickens, thymectomized and sublethally X-irradiated at hatching, showed increased titers of serum hemagglutinins to sheep erythrocytes (SRBC). Increased numbers of direct spleen plaque forming cells (PFC) were demonstrated with the Jerne technique using this antigen. Deliberate immunization i.v. with SRBC did not significantly increase the hemagglutinin titers or the numbers of direct or indirect PFCs per spleen. Spleen cells from thymectomized-irradiated chickens (TX) in tissue culture displayed impaired proliferative responses, measured as 3H-thymidine uptake, to phytohemagglutinin (PHA) and allogeneic spleen cells treated with mitomycin C. Also the proliferative response of spleen cells from immunized TX chickens to SRBC appeared deficient.
Cellular Reactions in Contact Photoallergy
Authors: Herman P.S. , Sams, Jr. W.M.
Published: July 2009

The nature of the cellular reactions underlying contact photoallergy to a salicylanilide compound has been examined. The typical dermal mononuclear cell infiltrate in positive photopatch tests has been shown to consist of cells staining negatively for lysosomal hydrolytic enzymes. Furthermore, peritoneal macrophages from salicylanilide-photosensitive guinea pigs lost their staining capacity for lysosomal enzymes when exposed to specific antigen. The relationship of these findings to the pathogenesis of cutaneous damage in photoallergy is discussed.
The Use of IgE Mediated Responses as a Pharmacologic Test System. The Effect of Disodium Cromoglycate in Respiratory and Cutaneous Reactions and on the Electrocardiograms of Rhesus Monkeys
Authors: Patterson R. , Talbot Catharine H. , Brandfonbrener M.
Published: July 2009

Disodium cromoglycate (DSCG) was used in a controlled laboratory study of an IgE-mediated, immediate-type, respiratory response in primates. The respiratory response to antigen was partially inhibited by DSCG. Systemic administration of DSCG did not inhibit active cutaneous reactivity to ascaris antigen or reverse passive cutaneous reactivity to anti-human IgE in rhesus monkeys, DSCG did not inhibit the respiratory eosinophil response which occurs after ascaris challenge in a highly reactive monkey. A possible explanation for the dissociation of the cutaneous and respiratory activity of DSCG in primate immediate-type responses may be the existence of more than one population of mast cells. The intravenous administration of DSCG resulted in transient aberrantly conducted premature beats in 3 normal rhesus monkeys.
The Effect of Prolonged Plasmapheresis on Immunoglobulins, other Serum Proteins, Delayed Hypersensitivity and Phytohemagglutinin-Induced Lymphocyte Transformation
Authors: Salvaggio J. , Arquembourg P. , Bickers J. , Bice D.
Published: July 2009

Serum protein concentrations and lymphocyte function, were determined in prisoner volunteers undergoing prolonged biweekly plasmapheresis and appropriate control subjects. Prolonged biweekly removal of 800 ml of plasma was well tolerated clinically. Neither circulating lymphocyte counts, PHA-induced in vitro lymphocyte 3H-TdR incorporation, or delayed hypersensitivity were affected. However, mean immunoglobulin, β1c-globulin and albumin levels decreased significantly during the initial year of plasmapheresis and individual values were below the accepted normal minimum range in over half the donors tested. Low levels of IgG, IgA, IgM, β1c-globulin and albumin were also detected in several ‘normal’ prisoner volunteers. These findings suggest that individual immunoglobulin and other serum protein concentrations should be quantitated initially to eliminate poor-risk donors, and monitored at intervals during the course of plasmapheresis.
Phylogeny of the Telencephalic Subventricular Zone in Sauropsids: Evidence for the Sequential Evolution of Pallial and Subpallial Subventricular Zones
Authors: Charvet Christine J. , Owerkowicz Tomasz , Striedter Georg F.
Published: July 2009

The telencephalon of birds and placental mammals harbors a proliferative subventricular zone (SVZ) in the subpallium as well as the pallium. Turtles, which are phylogenetically intermediate between bird, and mammals, exhibit at best a rudimentary SVZ. This suggests that SVZs evolved independently in mammals and birds, but it is not clear whether subpallial and pallial SVZs evolved with the origin of birds or in some earlier, non-avian sauropsid ancestor. To answer this question, we examined the brains of embryonic alligators (Ferguson stages 15–22) because crocodilians are the closest extant sister group to birds. To visualize the SVZ we labeled mitotic cells with antibodies against phosphorylated histone-3 (pH3) and proliferating cells with antibodies against proliferating cell nuclear antigen (PCNA). We found that the telencephalon of alligators contains an SVZ only in the subpallium. Because turtles, lizards and amphibians seem to lack SVZs, our finding suggests that a subpallial SVZ evolved in the last common ancestor of birds and crocodilians. Given that placental mammals and birds, but not marsupial mammals or reptiles, possess an SVZ within their pallium, we conclude that a pallial SVZ probably evolved independently in birds and placental mammals.
Australian Lungfish (Neoceratodus forsteri): A Missing Link in the Evolution of Complementary Side Biases for Predator Avoidance and Prey Capture
Authors: Lippolis G. , Joss J.M.P. , Rogers L.J.
Published: July 2009

Side biases in behavior, reflecting lateral specializations of the brain, are widespread amongst vertebrates. We studied laterality in the Australian lungfish (Neoceratodus forsteri) to gain insight into the evolution of the complementary specializations of predator avoidance (right hemisphere) and foraging behavior (left hemisphere). Because N. forsteri is the closest extant ancestor of the first land-dwelling vertebrates, knowledge of laterality in this species should provide a missing link in the transition from fish to tetrapods. Predator escape responses were elicited by generating pressure waves and a significant bias for C-start responses to the left side was found. This bias was unaffected by activity levels that change according to a diurnal cycle: activity is higher in the dark phase than the light phase. A complementary bias to turn to the right side was found during feeding behavior. This pattern of opposite-side specializations matches that known for fish, anurans, reptiles, birds and, as some evidence indicates, also mammals. Hence, we conclude that it is a homologous pattern of lateralization that evolved in early aquatic vertebrates and was retained as they made the transition to land-dwelling tetrapods.
Surgical Repositioning of Misplaced Subthalamic Electrodes in Parkinson’s Disease: Location of Effective and Ineffective Leads
Authors: Richardson R. Mark , Ostrem Jill L. , Starr Philip A.
Published: July 2009

There is no clear consensus regarding the optimal location for placing deep brain stimulation (DBS) electrodes within the subthalamic nucleus (STN) target region in Parkinson’s disease. In cases of poor symptom control or adverse effects following lead placement, leads presumed to be inadequately positioned may be corrected by surgical revision. We retrospectively analyzed a series of 8 patients who underwent surgical lead revision, to study the anatomic boundaries of effective lead placement. Reoperation to achieve changes of 2–5 mm in DBS lead position targeting the dorsolateral part of the STN produced significant clinical improvement in these patients. Improvements were due to better symptom control, reduction of stimulation-induced adverse effects or both. In many cases, leads in a peripheral zone of the STN were repositioned to a more central location within the sensorimotor territory of the nucleus. These results are contrasted with findings in other studies demonstrating optimal lead placement in STN border zones or neighboring white-matter tracts.
Different Suppressive Effects of Combined Cyclophosphamide-Antigen Treatment Compared with Exclusive Cyclophosphamide Treatment on Primary and Secondary Humoral Immune Reactivity
Authors: Herrlinger Jörg Dieter , Müller-Ruchholtz Wolfgang
Published: July 2009

The immunosuppressive effect of a combined treatment with antigen (C3H erythrocytes – ME) and cyclophosphamide (CY – dosage 65% LD50) has been studied in inbred CAP rats showing different degrees of immunological reactivity. When primary reactivity existed before treatment, this reactivity was not abolished but diminished. When weak secondary reactivity (after one antigen injection) existed before treatment this reactivity was abolished and again diminished primary reactivity was found. When strong secondary reactivity (after 4 antigen injections) existed before treatment selective unrespon-siveness was found during the 4 weeks following treatment. 12 weeks after treatment diminished primary reactivity was found again. When the same dose of CY was given without antigen no immunosuppressive effect could be seen – irrespective of whether primary, weak or strong secondary reactivity existed. The results indicate that in this model it is easier to induce selective unresponsiveness in sensitized than in nonsensitized rats and suggest that primed lymphocytes are more susceptible to a combined antigen-CY treatment than unprimed cells.
Contact Sensitivity in the Pig
Authors: Søeberg B. , Sumerska Tatjana , Binns R.M. , Balfour Brigid M.
Published: July 2009

Pigs were skin painted with the contact sensitizing agent DNFB and afferent lymph was collected for the next 24 h. The lymph cells carried a small amount of DNP and were able to sensitize 40% of homologous recipients. Peripheral blood lymphocytes conjugated with DNFB in vitro to the same degree as afferent lymph cells sensitized 80% of autologous and 40% of homologous recipients: lymphocytes conjugated at higher levels sensitized 75% of animals in each group. Lightly conjugated cells were capable of survival and able to respond to stimulation by mitogens and their ability to sensitize autologous recipients was abolished by heat killing. Highly conjugated cells were not capable of survival, their sensitizing ability was not altered by heat killing and they were able to sensitize incompatible recipients. It is suggested that highly conjugated cells sensitize by a different mechanism which depends on the cooperation of non-lymphocytic cells, not easily mobilized from lymphoid tissue.
Suppression of Delayed Hypersensitivity to the Hapten by Induction of Tolerance to the Carrier
Authors: Neveu P.J.
Published: July 2009

Delayed hypersensitivity reactions (DHR) and anaphylactic reactions to carrier and hapten determinants were studied in guinea pigs immunized with DNP-mycobacterium and rendered partially tolerant to the carrier by a single intravenous injection of myco-bacterium prior to immunization. The results clearly show that the induction of depressed DHR to mycobacterium leads to a suppression of DHR to the hapten while no depression of anaphylaxis to the hapten is observed. It is proposed that the tolerogenic treatment acts at the macrophage level rather than at the T cell level.
Modification of Prostaglandin and Thromboxane Release by Immunological Sensitisation and Successive Immunological Challenges from Guinea-Pig Lung
Authors: Boot J.R. , Cockerill A.F. , Dawson W. , Mallen D.N.B. , Osborne D.J.
Published: July 2009

The release of prostaglandins (PGs) and thromboxanes (Txs) from perfused guinea pig lungs was investigated during different immunological states. The major product released from normal lungs perfused with exogenous arachidonic acid was 6-oxo-PGF1α. The procedure of sensitisation to specific antigen resulted in an increase in the release of 15-oxo-13,14-dihydro-TxB2 and a decrease in the release of 6-oxo-PGF1α- and 6,15-dioxo-13,14-dihydro-PGF1α from lungs perfused with arachidonic acid. The relative amount of 15-oxo-13,14-dihydro-TxB2 released progressively increased with the number of immunological challenges with both exogenous and endogenously derived substrate, arachidonic acid. This change in response to successive immunological challenges may represent a protective mechanism to prevent parent Txs and PGs entering the systemic circulation.
Selective Killing of Mitogen-Induced Transformed Cells by Quinine Sulfate in vitro
Authors: Gold Eugene F. , Ben-Efraim Shlomo
Published: July 2009

Increase in incorporation of 3H-thymidine ([3H]-Tdr) in blast-transformed cells was induced in vitro by either lipopolysaccharide or concanavalin A (Con A) in spleen cells of Balb/c mice and by Con A in rabbit peripheral lymphocytes. Small lymphocytes were not affected by the addition of quinine to the medium. This was shown by a dye exclusion test and by mitogen stimulation after exposure and removal of quinine from the medium. On the other hand, immunoblasts were not formed in lymphocyte cultures containing both quinine and the cell mitogen. The degree of [3H]-Tdr incorporation after mitogenic stimulation was also markedly reduced by subsequent addition of quinine. An incubation period of at least 5 h was required for the expression of quinine effect. It is concluded that quinine acts as a cytotoxic agent for immunoblasts in vitro.
Histamine in Nasal Secretions
Authors: Eggleston Peyton A. , Hendley Owen , Gwaltney, jr. Jack M. , Eggleston Angela W. , Leavell, jr. Byrd S.
Published: July 2009

The histamine content of secretions collected by small-volume nasal washes was assayed by a spectrophotofluorometric method. A wide range of histamine concentrations (< 5–1, 519 ng/ml) was found. The mean concentration in secretions from normal individuals (91 ng/ml) was not significantly different from that found in allergic individuals (51 ng/ml). Females had significantly lower concentrations than did males. Sequential sampling in normals and allergies showed a great deal of daily variation in histamine content. This technically simple method may prove useful in examining the epidemiology and pathophysiology of allergic rhinitis.
Pregnancy-Associated Plasma Proteins in Pregnant and Pseudopregnant Rats
Authors: Lin Tsu-Hui , Sperling Frederik , Lin Tsue-Ming , Halbert Seymour P.
Published: July 2009

As in the human, the rat pregnancy-associated plasma proteins consisted of four distinct entities as revealed by immunological methods. All showed gradual increases during gestation and rapid disappearance postpartum. They could be physicochemically, although not immunologically, tentatively related to the human pregnancy proteins. None of them was detectable in the serum of rats at various stages of pseudopregnancy, nor in nonpregnant rats.
Inhibition of Human Complement Components by Loxosceles reclusa Venom
Authors: Futrell Josephine M. , Morgan Paul N.
Published: July 2009

Venom from the brown recluse spider, Loxosceles reclusa, was capable of inactivation human C1–C7 in vitro. This inactivation occurred if venom was added to fresh adult human serum, human cord serum, or functionally pure specific human components. Optimal incubation conditions for the inactivation of each component were determined and were found generally to be in the range of 25 or 37 °C for 30–60 min. The alternative complement pathway did not appear to be involved, since C1, C4, and C2 were readily inactivated, and inactivation took place in sera depleted of factor B of the properdin system. Venom-induced inactivation appeared to require few, if any, serum cofactors, because, with the possible exception of C2, functionally pure components, as well as those in sera, were readily inactivated.
Lymphocyte-Potentiating Factor from Human Peripheral Blood Adherent Cells
Authors: Masuzawa Yasuo , Sawada Setsuko , Sawada Jun-ichi , Osawa Toshiaki
Published: July 2009

Low-molecular-weight factor, which can restore the diminished concanavalin A (Con A) response of adherent-cell-depleted human peripheral blood lymphocytes, was partially purified from the culture supernatant of human peripheral blood adherent cells by ion-exchange column chromatography, gel filtration and preparative paper chromatography. This factor apparently has a mechanism of action distinct from that of 2-mercaptoethanol. It affects the cells just before the onset of the DNA synthesis possibly as one of the second signals in the Con-A-induced activation of human peripheral blood lymphocytes. However, it was demonstrated that the effective activation of lymphocytes also required the presentation of Con A by adherent cells to lymphocytes at the triggering stage of the activation, indicating that adherent cells have two distinct functions in the Con-A-induced activation of lymphocytes, i. e. the presentation of Con A to lymphocytes and the elaboration of soluble factors.
Two Small Lymphocyte Subpopulations in Human Peripheral Blood
Authors: Hokland Peter , Hokland Marianne , Heron Iver
Published: July 2009

Two small lymphocyte subpopulations from human peripheral blood were produced by rosette sedimentation procedures, and tested for in vitro functions by stimulation with mitogens, PPD and allogeneic lymphocytes, and for effector capacities in ADCC. The non-T, non-Fc subpopulation had previously been found to be a Smlg+ fraction which did not aquire new surface markers during unstimulated culture, did not respond to mitogens, PPD or allogeneic cells but were potent MLC stimulators. In addition, they were poor ADCC effector cells. The non-T, non-B (‘Null’) cells, which showed varying surface marker profiles from donor to donor, were able to respond to mitogens and PPD, but were weak MLC responders. Potent ADCC effector capacity was, however, found to be exhibited by this subpopulation.
Antigens in Penicillin Allergy
Authors: Ahlstedt S. , Kristofferson A. , Pettersson E.
Published: July 2009

Using a radioimmunoassay, it was shown that commercially available ampicillin preparations often contain penicilloylated high molecular weight impurities. These possess immunological activities and stimulate penicilloyl-specific antibody formation in mice treated according to a therapeutic schedule. Using purified and experimentally contaminated preparations it was also found that exposure of the animals to Escherichia coli and Bordetella pertussis bacteria could increase the antibody formation to small amounts of impurities. In addition, penicilloylated antigen could be recorded in serum from treated animals. The antigen formed by penicilloylation in vivo, however, was very weak and did not induce much antibody formation when injected together with Freund’s adjuvant in mice or rabbits.
Effect of Quantity and Quality of IgG Antibodies on Blocking of Allergenic Histamine Release in vitro
Authors: Schumacher Michael J. , Jeffery Sandra E.
Published: July 2009

In a study of the protective role of IgG antibodies in allergen injection therapy, serum antibodies to timothy grass allergens were raised in rabbits and tested for inhibition of histamine release from basophils of grass pollen-sensitive human subjects. Rabbit sera were not inhibitory until late in the immune response when large amounts of relatively low affinity IgG antibodies were detected by primary binding. Inhibition of histamine release by late sera required preincubation of allergen and antibody prior to addition of sensitive basophils, and could not be demonstrated when basophils and IgG antibodies had simultaneous access to allergen. Hence intravascular inhibition of mediator release in allergen-treated patients may require high affinity IgG antibodies. The predominantly low affinity of antibodies raised in the rabbits precluded testing of this possibility.
Influence of Carbonyl Iron Treatment on Lymphocyte Subpopulations
Authors: Rumpold H. , Kraft D. , Scheiner O. , Radaszkiewicz T.
Published: July 2009

The influence of carbonyl iron treatment on different human mononuclear cell subsets was investigated. There is evidence that, in addition to removal of phagocytic cells, lymphocytes are depleted, B cells being more affected than other subpopulations.
Standardization of Radioallergosorbent Test (RAST) and Allergen Extracts in Terms of the WHO Standard for IgE
Authors: Huggins K.G. , Roitt I.M. , Brostoff J. , Taylor W.A.
Published: July 2009

An 131I-labelled IgE myeloma, standardized against the WHO reference serum for IgE was bound in varying concentrations to discs bearing anti-human light chain. These were used to construct a calibration curve for the subsequent binding of 125I-labelled anti-IgE, thus relating 125I counts to WHO IgE units. The calibrated anti-IgE could then be used to measure the actual amount of specific IgE bound to an allergen disc in the radioallergosorbent test. Using this standardized system, soluble allergen extracts could then be assayed by their ability to inhibit the binding of a defined amount of specific IgE, thereby enabling their activity to be expressed in WHO IgE units.
Study of Pregnancy-Associated alpha2-Glycoprotein in Relation to Populations of Human Blood Leucocytes
Authors: Thomson A.W. , Hunter Christine B.J. , Cruickshank Norma , Horne C.H.W.
Published: July 2009

Pregnancy-associated α2-glycoprotein (α2-PAG) was identified by immunofluorescence on the surface membrane of mononuclear cells from normal individuals with an extensive range of plasma concentrations of the glycoprotein. The incidence of positive cells did not correlate with plasma levels but was significantly raised in chronic lymphocytic leukaemia. Anti-α2-PAG antibody interfered with E and Fc rosette formation but not with production of C3 rosettes. A large proportion of C3 receptor-bearing cells (B lymphocytes) but only a tiny fraction of E-rosette-forming cells (T lymphocytes) were positive for the protein. Antibody directed against human la antigen markedly reduced staining for α2-PAG.
Cellular Cooperation in Lymphocyte Activation
Authors: Kasahara Tadashi , Kin Kohjin , Itoh Yoshihisa , Kawai Tadashi , Morita Mamoru , Shioiri-Nakano Kohei
Published: July 2009

Human T and B lymphocytes were highly purified from tonsil and peripheral blood, and their proliferative responses to various mitogens were studied. T cells [T(III)] were purified by filtration through a nylon fiber column (NC), followed by a double cycle of E rosette formation and Ficoll-Paque sedimentation. B cells [B(VIII)] were obtained from the NC-retained fraction by twice removal of E rosette forming cells. A second T cell preparation [T(VI)] was obtained from the NC-retained fraction. Purified T(III) and B(VIII) preparations contained less than 1% of other cell types. Phytohemagglutinin, pokeweed mitogen and concanavalin A (T mitogens) stimulated T(III) and T(VI) well, but had no effect upon B(VIII). Staphylococcus aureus Cowan I (SpA) and insolubilized protein A stimulated B(VIII) in the complete absence of T cells. Under the reconstituted culture of T(III) and B(VIII), responses to T mitogens were greatly enhanced by the addition of B(VIII). This enhancing effect was mainly caused by B cells and was not diminished by mitomycin treatment, suggesting that the observed T-B cooperation was attributable to direct cell-to-cell interaction. B(VIII) were also significantly stimulated by T mitogens in the presence of smallest number of T cells. SpA stimulated B(VIII) in proportion of their cell number independent of the addition of T cells. On the other hand, T(VI), which contained 3–10% B cells, showed rather higher response to T mitogens than T(III), failed to show coorepation with B(VIII).
Effect of Cobra Venom Factor on the Response of Wistar-Furth Rats to the Gross-Virus-Induced (C58NT)D Lymphoma
Authors: Mizoguchi Yasuhiro , Osler Araham G.
Published: July 2009

Wistar-Furth rats were injected with the anticomplementary cobra venom factor at the time of challenge with the Gross-virus-induced (C58NT)D lymphoma. Complement depletion and/or activation of the complement system in these animals led to the following findings: Multiplication of the tumor cells in vivo was accelerated and mortality rates were enhanced. In addition, serum levels of the immunoglobulins which mediate antibody-dependent cellular cytotoxicity were depressed.
Circulating Immune Complexes in Acute Uveitis: A Possible Association with the Histocompatibility Complex Locus Antigen B27
Authors: Andrews Brian S. , Mclntosh Jill , Petts Valerie , Penny Ronald
Published: July 2009

39 patients with acute anterior uveitis were investigated for the presence of circulating immune complexes (IC) and correlation with the major histocompatibility complex antigen B27 (HLA–B27). ICs were demonstrated by a number of techniques including rheumatoid factor, complement (C) activation, anticomplementary activity, cryoglobulins, inhibition of IgG–EA rosette formation and neutrophil chemotactic index (NCI) in plasma. ICs were most frequently detected in HLA-B27-negative patients. These results indicate that deposition of circulating ICs may be involved in the pathogenesis of acute anterior uveitis, especially in HLA-B27-negative patients.
Attempts to Modulate the Immune Response to a Hapten-Carrier Complex with Various Hapten-Containing Compounds
Authors: Neveu P.J.
Published: July 2009

The immune response to a hapten-carrier conjugate appears to be a complex phenomenon where reactions of the T-cell population are not restricted to the carrier and where the reactions of the B-cell population are not limited to the hapten determinant of the antigen molecule. To get a better understanding of the different cell interactions during the immune response to a hapten-carrier complex, the effects of immunogenic or tolerogenic injections of various hapten-containing compounds on the responses induced by immunization with the same hapten coupled to protein carriers were studied. The results indicate that T cells involved in delayed hypersensitivity and T cells involved in contact dermatitis could belong to distinct subclasses and confirm that hapten and carrier moieties of the antigen molecule could compete, probably at the macrophage level, for both delayed hypersensitivity to the carrier and antibody synthesis to the hapten.
The Allergenic Structure of Allergen M from Cod
Authors: Apold J. , Elsayed S. , Aukrust L. , Bennich H.
Published: July 2009

Fragments TM 1 (75 amino acid residues) and TM 2 (38 amino acid residues), and 3 other polypeptides (range 16–25 amino acid residues) of Allergen M from cod were shown to be active in rabbit IgG-mediated reactions. The same peptides were previously found to possess reactivity in IgE-mediated reactions, thus suggesting a structural relationship between their antigenic and allergenic determinants.
Allergenicity of Concanavalin A in Mice
Authors: Mitchell Graham F. , Clarke Adrienne E.
Published: July 2009

Concanavalin A (Con A) is a potent allergen in certain strains of mice and in particularly the H-2Kk mice, A/J, CBA/H, and C3H/He. Using a dose of 100 μg, the subcutaneous route of injection was the most effective means of inducing high, persistent titers of T cell-dependent circulating anti-Con A reagins without the addition of the classical ‘ΙgE adjuvants’, aluminium hydroxide and Bordetella pertussis vaccine. Haptenated Con A induced reagins with antihapten specificity. In the discussion, one possible contributing factor in Con A allergenicity in genetically responder strains of mice is emphasised, namely, persistence in subcutaneous injection sites.
Nephelometric Detection of Soluble Immune Complexes: Methodology and Clinical Applications
Authors: Virella Gabriel , Hipp Win Anne , John, jr. Joseph F. , Kahaleh B. , Ford Marsha , Fudenberg Hugh
Published: July 2009

We have developed a method for the detection of immune complexes by laser nephelometry which is simple, reproducible, suitable for automation, and generally adaptable for diagnostic testing. Light dispersion by antigen-antibody complexes in the test samples is measured after addition of polymeric buffer, which enhances the aggregation of complexes but does not significantly affect unbound immunoglobulins. The method was used to measure immune complexes formed in vitro by incubation of tetanus toxoid with serum from a rabbit previously hyperimmunized with the same antigen, and to compare the. levels of immune complexes in human sera obtained from normal adults and from 37 patients with collagen vascular diseases or endocarditis. When precautions were taken to avoid interference produced by the presence of lipoproteins or by freezing of the samples, the results obtained with human sera were consistent with those expected for normal controls and for patients with conditions thought to be associated with the presence of soluble immune complexes.
Eosinophil Chemotactic Factor
Authors: Tesch H. , König W. , Frickhofen N.
Published: July 2009

An eosinophil chemotactic factor (ECF) can be released from human polymorphonuclear neutrophils by arachidonic acid (AA), its methyl ester, but not by other derivatives such as AA ethyl ester and arachidonyl acetate. The ECF is highly specific for eosinophils and does not attract polymorphonuclear neutrophils. A dose-dependent non-cytotoxic ECF release induced by AA can be obtained from human polymorphonuclear neutrophils from a lymphocyte-monocyte-basophil suspension, from rat basophil leukemia cells, but not from human lymphocytes. Kinetic studies demonstrate that ECF release occurs rapidly with an early rise and steep fall-off at later times of secretion. The amount of ECF release is dependent on pH, temperature and medium which is used for stimulation. Gel filtration analysis as well as subcellular fractionation studies suggest that the AA-induced ECF is a biological activity either distinct from AA and its split products or representing a known or unknown conversion product of AA with potent effects on eosinophils at minimal concentrations. AA may therefore represent an important mechanism of cell activation.
Clinical Comparison of Skin Testing and the Radioallergosorbent Test in Dog-Sensitive Patients Using Mixed and Breed-Specific Antigens
Authors: Meriney David K. , Wallace Dana , Miller Jeffrey , Goel Zarina A. , Grieco Michael H.
Published: July 2009

A study of clinical history, intradermal test end points and RAST values with six different dog antigens was made in 20 patients and 5 control subjects. Skin testing was found to be more useful clinically than the RAST. Considerable variability among mixed epidermal extracts was noted. There was no apparent advantage to testing with three individual-breed extracts studied, compared to the most potent mixed epidermal antigen. The results of this study suggest that further efforts toward standardization of potency, methods of preparation and, possibly, breed composition of dog allergenic extracts are required to develop improved allergens for clinical use.
Simultaneous Generation of Tuberculin-Type and Cutaneous Basophilic Hypersensitivity at Separate Sites in the Guinea Pig
Authors: Leonard Edward J. , Lett-Brown Michael A. , Askenase Philip W.
Published: July 2009

Strain-2 guinea pigs received two separate intradermal immunizations. The first was a mixture of living BCG (Phipps strain of bacille Calmette-Guerin) and syngeneic line-10 hepatoma cells. The second, administered after 6 weeks or more, was keyhole limpet hemocyanin (KLH) in saline. One week after the second injection, the animals were skin tested at separate sites with tumor cells, purified protein derivative of tuberculin (PPD) and KLH. Delayed cutaneous hypersensitivity (DCH) reactions were evident by 24 h. At this time the reaction sites were processed by histological methods that preserved basophil morphology and staining qualities. Three distinctive infiltrates were elicited by the different antigens. In addition to the mononuclear cell infiltrate common to all three reactions, the KLH site had a high concentration of basophils and few neutrophils, characteristic of cutaneous basophilic hypersensitivity (CBH); the PPD site had practically no basophils but many neutrophils; and the tumor cell reaction was predominantly mononuclear, with small numbers of basophils and virtually no neutrophils. Simultaneous generation of different DCH reactions in the same animal and quantitative description of the cellular infiltrate provided a basis for DCH classifications, with KLH CBH and tuberculin reactions as standards for comparison. Since challenge with three antigens at separate sites in the same animal generated DCH reactions with widely differing patterns of cellular infiltration, the reason for the differences must occur at the local sites or, if circulating, must be antigen-specific.
Rejection of Tumor Cells in vitro: Morphological Studies on Killer T Cells and Damaged Tumor Cells
Authors: Berczi I. , Kovács K. , Horváth E. , Sehon A.H.
Published: July 2009

The in vitro destruction of a methylcholanthrene-induced guinea pig sarcoma (MC-D) by killer T lymphocytes was investigated by light and electron microscopy. Various degrees of cell damage ranging from slight to extensive were observed. In cells with slight injury, dilatation, vesiculation, fragmentation and degeneration of the rough surfaced endoplasmic reticulum were the most characteristic findings. In cells with extensive injury, widespread nuclear and cytoplasmic alterations were evident and many of these cells were fragmented into smaller portions and finally transformed into granular membranous and amorphous debris. Cytoplasmic vacuoles filled with electron-lucent material were frequent in extensively damaged cells. Killer lymphocytes resembled closely antibody-forming plasma cells when examined with light microscopy but lacked the extensive network of rough surfaced endoplasmic reticulum, and did not produce immunoglobulin. It is suggested that these extensively differentiated T-derived killer cells are end cells similar to those of B lymphocyte-derived plasma cells. Viral particles resembling closely C-type viruses were observed in mixed killer cell MC-D cultures.
Non-Immunogenicity of a Purified Sodium Hyaluronate Preparation in Man
Authors: Richter A.W. , Ryde E.M. , Zetterström E.O.
Published: July 2009

The immunogenicity of a sodium hyaluronate preparation for clinical use (Healon, Healonid, Pharmacia AB, Sweden) in ophthalmology and certain joint diseases has been tested in man. For immunization, two subcutaneous injections of 10 mg of sodium hyaluronate were given at an interval of 1 week. The following criteria were used as indicators of immunogenicity: skin prick test, microprecipitation test and complement analyses. No evidence for immunogenic properties was obtained in any of these tests. This refers to sodium hyaluronate itself and to the trace amounts of protein components contained in the preparation.
Lateral and Transmembrane Redistribution of Tissue-Specific Antigens in Single Cells and Monolayers
Authors: Whiteside Theresa L. , Manski W.J.
Published: July 2009

Tissue-specific antigens in the membranes of corneal endothelial cells react with anti-tissue antibodies only in metabolically active monolayers and dispersed cells. After metabolic inhibition by exposure of these preparations to cold, the antigen-antibody complexes, like free antigens, undergo transmembrane redistribution leading to their internalization by the cells. This transmembrane redistribution is reversible and can be followed by using fluorescein-labeled antibodies. Reexpression of the complexes on the cell surfaces occurs after return from metabolic inhibition to metabolic activity. Dispersed corneal endothelial cells are also capable of lateral redistribution (capping) of the complexes although cells in monolayers do not share this capability. Capping in the dispersed cells occurs only at ambient temperatures and, because it results in shedding of the complexes, is irreversible. The data indicate that macromolecules in the membranes of cells organized in tissues are restricted in their movement as compared to the macromolecules of cells functioning in a dispersed state.
Collection of Lymph from Single Lymph Nodes and the Intestines of Fetal Lambs in utero
Authors: Cahill R.N.P. , Poskitt D.C. , Heron I. , Trnka Z.
Published: July 2009

Techniques for establishing chronic lymphatic fistulae in the intestinal and prescapular lymphatic ducts of fetal lambs during the last third of gestation are described. Despite the absence of antibody, immunoglobulin and extrinsic antigen, the number of recirculating lymphocytes increases considerably through gestation. Both thymus-derived and surface Ig-bearing B lymphocytes are present in the fetal recirculating pool and they appear to increase in number at the same rate.
Cross-Reactivity of the O Antigens among Haemophilus influenzae Type b Strains
Authors: Branefors P.
Published: July 2009

The double-immunodiffusion technique was used to compare the O antigens of 18 meningeai Haemophilus influenzae type b strains with each other and with H. influenzae strains representing the capsular types a–f. The O antigens of the meningeal strains and the reference type b strain (strain Rab) cross-reacted to a large extent, while only a few cross-reactions were demonstrable with the other serotypes.
Characterization of Lymphocytes Which Inhibit Proliferation of Human T Cells Exposed to Lymphocyte-Derived Mitogenic Factors
Authors: Blomgren Henric
Published: July 2009

Culture supernatants of PHA-activated human lymphocytes (active SUPs) contain factors which are strongly mitogenic for fractionated peripheral T cells. This stimulation is suppressed by certain non-T lymphocytes. It is shown that these suppressor cells can inhibit an ongoing response of T cells to active SUP and that this inhibition is reversible. Using various rosette sedimentation techniques for fractionating subpopulations of lymphocytes it is concluded that the suppressor cells lack membrane-associated receptors for C′3 but possess receptors for the Fc part of IgG. This subset of lymphocytes may be an important regulator of lymphocyte proliferation during immune responses.
Atopic Dermatitis: A Disease of General Vasoactive Mediator Dysregulation
Authors: Ring Johannes
Published: July 2009

A simple hypothesis trying to explain the complex etiology of atopic dermatitis is presented. Based on the facts of various known immunologic and autonomic nervous system abnormalities the possible role of vasoactive mediators in this disease is stressed. There are several factors which favour a continuous tendency to release vasoactive substances, as for example histamine; the immunologically, IgE-mediated histamine release is only one of them. Basophils of atopic individuals show increased ‘releasability’ after stimulation with a variety of non-immunologic stimuli. Together with this increased releasability, a deficiency in control systems, as in the cyclic AMP-dependent mechanisms, is known, also favouring increased histamine release. Histamine as one of the mediators not only acts upon the capillaries, the bronchial and circulatory system, but on lymphocytes too: it is known that especially T cell functions can be inhibited by histamine in vitro and in vivo. Suppressor T cells are particularly sensitive to histamine being most likely the population of T lymphocytes bearing histamine receptors. In atopic dermatitis a specifically increased sensitivity of T cells to histamine has been described. Therefore, increased levels of histamine could explain the well-known cell-mediated immune deficiency in patients with atopic dermatitis as well as possibly their increased tendency to produce IgE antibodies. The latter hypothesis is based on animal experiments which clearly show that IgE production is favoured by a deficiency in the suppressor T cell system. This hypothesis puts together the most important pathological findings in this disease; a genetic defect as basis of ‘leaky’ mast cells and basophils seems likely.