bluuebunny/crossref_metadata_2025 huggingface dataset:
Synergy between adjuvant arthritis and collagen-induced arthritis in rats.
Authors: Taurog J D , Kerwar S S , McReynolds R A , Sandberg G P , Leary S L , Mahowald M L
Published: June 2004

Adjuvant arthritis (AA) in rats is susceptible to cell-mediated passive transfer. Collagen-induced arthritis (CIA) in rats is susceptible to passive transfer with antibody to type II collagen. We report here the development of strikingly severe arthritis in Lewis rats as the result of synergy between passively transferred antibody to type II collagen from rats with CIA and concanavalin A (Con A)-stimulated lymph node or spleen cells from syngeneic rats with AA. Similar synergy was seen in rats with AA given anticollagen antibody, in rats with CIA given Con A-stimulated adjuvant spleen cells, and in rats actively immunized with CII and complete Freund's adjuvant. The synergistic process caused a very severe polyarthritis, characterized by marked swelling and erythema in all the joints of the distal extremities, with histologic and radiographic evidence of early, extensive erosion of articular cartilage. Synergy was apparent if the lymphoid cells from AA rats were given up to 1 mo after a single injection of anticollagen antibody. No synergy was seen when normal rat immunoglobulin or anti-ovalbumin antibody was substituted for anticollagen antibody, when Con A-stimulated lymphoid cells from normal rats or donors with CIA were used, or when Con A-stimulated AA lymphoid cells were irradiated before transfer. Synergy between separate immune effector mechanisms may represent a general phenomenon in the pathogenesis of inflammatory joint disease.
Synergism between T and non-T cells in the in vivo induction and in vitro expression of graft-vs.-host disease-induced natural suppressor cells.
Authors: Maier T , Holda J H , Claman H N
Published: June 2004

We have been studying the mitogen hyporesponsiveness and immunosuppression induced in chronic murine graft-vs.-host disease (GVHD) induced across minor histocompatibility (MiHA) barriers. In this system, donor and recipient mice are major histocompatibility complex- and mls-identical, and are nonreactive in primary mixed leukocyte reactions. Spleen cells from B10.D2 (H-2d, mls b) mice were injected into irradiated (600 rad) BALB/c (H-2d, mls b) recipients. Recipient spleen cells are hyporesponsive to mitogens, and contain natural suppressor (NS) cells. We investigated the cellular requirements for both the in vivo induction and the in vitro expression of this GVH suppression. T cells are required in the graft, but they are not sufficient to induce suppression, and a non-T cell population is also required for maximum induction in vivo. T cells are also required for the maximum expression of NS cell suppressive ability in vitro. Early in the course of GVH, the suppressor cells are able to suppress the Con A and LPS response of all mouse strains tested (except for the relative difficulty in suppressing the B10.D2 LPS response). Later, they become almost completely unable to suppress the B10.D2 LPS response; while still being able to suppress the Con A and LPS response of all other strains tested (including the B10.D2 Con A response). This inability to suppress a B10.D2 LPS response can be brought back to almost complete suppression by the addition of concanavalin A supernatant (CAS). We present a hypothesis to explain what may be a common mechanism for GVH-induced suppression, total lymphoid irradiation-induced suppression, and neonatal tolerance. These situations all include rapidly proliferating lymphohematopoietic stem cell populations, and also have large numbers of NS cells. NS cells can suppress proliferating lymphoid populations, and their development and activity are greatly enhanced by T cell signals such as are supplied by donor T cells in chronic GVHD. Thus, NS cells may feed back on and downregulate self-reactive T cells or T cells responding to introduced foreign antigens.
Purification to homogeneity of a high molecular weight human B cell growth factor; demonstration of specific binding to activated B cells; and development of a monoclonal antibody to the factor.
Authors: Ambrus J L , Jurgensen C H , Brown E J , Fauci A S
Published: June 2004

High molecular weight B cell growth factor (HMW-BCGF) produced by a T cell line was purified to homogeneity and demonstrated to bind specifically to activated human B cells. A monoclonal antibody to HMW-BCGF was developed that (a) specifically inhibited the activity of HMW-BCGF in enhancing B cell proliferation, (b) specifically bound to HMW-BCGF in Western blots, (c) specifically absorbed HMW-BCGF activity from culture supernatants, and (d) specifically absorbed an internally labeled protein from T-ALL supernatant which comigrates with HMW-BCGF on sodium dodecyl sulfate-polyacrylamide gels. This antibody should help in cloning the gene for HMW-BCGF and further exploring the physiologic roles of HMW-BCGF.
Anticlonotypic monoclonal antibodies induce proliferation of clonotype-positive T cells in peripheral blood human T lymphocytes. Evidence for a phenotypic (T4/T8) heterogeneity of the clonotype-positive proliferating cells.
Authors: Moretta A , Pantaleo G , Lopez-Botet M , Mingari M C , Moretta L
Published: June 2004

Three previously selected monoclonal antibodies (mAb) directed against the clonotypic structure of a variant (termed JA3) of the interleukin 2 (IL-2)-producing Jurkat leukemia cell line (anti-JTi1-3 mAb) were found to induce an adherent cell-dependent proliferation of peripheral blood T cells in 20 different donors. Unlike the early cell proliferation induced by anti-T3 mAb, anti-JTi mAb-induced proliferation was detectable at day 5-6 of culture and reached peak levels at day 7-9. Less than 1% JTi+ cells were consistently detected in the starting peripheral blood lymphocytes or in control cultures in which cells were stimulated with anti-T3, phytohemagglutinin, or allogeneic cells. However, JTi+ cells were found in increasing proportions after culture with anti-JTi mAb and they were mostly represented by large blast cells expressing either the T4 or the T8 antigen, together with typical activation antigens including HLA-DR, IL-2 receptor, and 4F2. Immunoprecipitation experiments and sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that anti-JTi-reactive molecules present on antibody-stimulated lymphocytes or on JA3 cells were similar, disulphide-linked heterodimeric structures.
Helper T cells reacting to idiotype on IgG but not IgM.
Authors: Saito T , Rajewsky K
Published: June 2004

Immunization with an IgG1 but not an IgM monoclonal anti-NP (4-hydroxy-3-nitrophenyl acetyl) antibody induced idiotype-recognizing T helper cells, although these two antibodies carry the same variable regions. The T cells appear to react to an idiotype on the IgG1 but not the IgM antibody. They selectively enhance the expression of that idiotype in the IgG1 fraction of an in vitro anti-NP response.
Lack of binding of bacterial lipopolysaccharide to mouse lung macrophages and restoration of binding by gamma interferon.
Authors: Akagawa K S , Tokunaga T
Published: June 2004

Although peritoneal resident macrophages (PRM) or peritoneal exudate macrophages (PEM) were activated by lipopolysaccharide (LPS) to kill tumor cells in vitro, lung macrophages (LM) obtained by mincing lung tissues or by harvesting bronchial lavage were not activated by LPS under any experimental conditions, i.e., different LPS concentrations, incubation times and cytotoxicity assay methods. The unresponsiveness of LM to LPS was seen in all of the mouse strains tested. Treatment of LM with indomethacin did not affect the unresponsiveness, although it greatly augmented the cytotoxicity of PRM stimulated with LPS. LM treated in vitro with crude lymphokines (LK) did not show cytotoxicity, but became sensitive to LPS and cytotoxic for tumor cells. LM treated first with crude LK and then with LPS were cytotoxic, but LM treated first with LPS and then with crude LK were not. The ability of crude LK to render LM responsive to LPS was neutralized by rabbit anti-mouse gamma interferon (IFN-gamma) antiserum but not by anti-mouse IFN-(alpha + beta) antiserum. LM treated with recombinant murine IFN-gamma became responsive to LPS and showed cytotoxicity. LM were resistant to direct toxicity of LPS under conditions in which significant populations of PRM and PEM died. However, LM became sensitive to direct toxicity of LPS by treatment with crude LK or recombinant murine IFN-gamma. Fluorescence microscopy showed that almost all PRM and PEM were stained with fluorescein isothiocyanate (FITC)-LPS, while less than 5% of the LM were stained. Instead, approximately 60% of the LM treated with the crude LK or recombinant IFN-gamma for 20 h were stained with FITC-LPS. Fluorescence-activated cell sorter (FACS) analysis confirmed this result. The staining of IFN-gamma treated LM with FITC-LPS was inhibited by polymyxin B or unlabeled LPS. These results suggest that the defective responsiveness of LM to LPS is due to the lack or very low expression of LPS-binding sites on the cell surface and that in vitro treatment with IFN-gamma brings about the expression of them and renders LM responsive to LPS.
Monoclonal antibody characterization of a unique immune response control locus between H-2S and D.
Authors: Shapiro L H , Dugan E S , Neiderhuber J E
Published: June 2004

The primary in vitro antibody response to the type 2 antigen, trinitrophenyl (TNP)-Ficoll, is controlled by two complementing loci in the H-2 region of the mouse major histocompatibility complex (MHC). High responder alleles at both loci are necessary for a high responder phenotype. Previous studies mapped one locus of control to the I-A subregion. In this report we demonstrate by recombinant analysis that the second locus of control is located between the H-2S and D regions. A comparison of responses in the B10.BAR6, B10.BAR10, and B10.BAR11 strains defined a locus controlling the response to TNP-Ficoll in a single haplotype, bounded on the left by the crossover event in the B10.BAR10 and on the right by the crossover event in the B10.BAR6 strain. A monoclonal antibody directed against this right-hand region of control has been produced (48.21.7) that blocks the response to TNP-Ficoll at the level of the antigen-presenting cell. The monoclonal antibody 48-21.7 is specific for the high responder b allele at the right-hand locus and did not inhibit responses to other protein antigens tested. The immune response to TNP-Ficoll was not inhibited by monoclonal antibodies that react with H-2Db or Qa-2 specificities, suggesting that the TNP-Ficoll response is controlled by a unique locus located between H-2S and D. Finally, 48-21.7 recognizes and precipitates a unique product of approximately 40,000 mol wt that is distinct from the H-2D region product recognized by the monoclonal antibody B22/249.
Natural killer (NK) cell-derived hematopoietic colony-inhibiting activity and NK cytotoxic factor. Relationship with tumor necrosis factor and synergism with immune interferon.
Authors: Degliantoni G , Murphy M , Kobayashi M , Francis M K , Perussia B , Trinchieri G
Published: June 2004

We characterize the natural killer (NK) cell colony-inhibiting activity (CIA) produced in supernatants from cultures of human peripheral blood lymphocytes (PBL) with NK-sensitive target cell lines, and study its relationship with NK cell-derived cytotoxic factor (NKCF). Using monoclonal antibodies (mAb) specific for NK cells or other lymphocyte populations, we unambiguously identify NK cells as the only PBL subset able to produce both NKCF and NK-CIA. We present functional and biochemical data suggesting that NKCF and NK-CIA represent the same molecule: (a) a highly significant positive correlation exists between the quantity of NKCF and NK-CIA in supernatants independently produced by different PBL subsets; (b) both NK-CIA and NKCF are induced by culture of PBL with NK-sensitive, but not with NK-insensitive cell lines, and with HLA-DR+ bone marrow cells; (c) both NKCF and NK-CIA are absorbed on the same cell lines or bone marrow cell types; (d) the two activities coelute in the same gel filtration fractions; (e) D-mannose-6-phosphate blocks both NKCF and NK-CIA activity, and prevents their absorption by K562 cells; and (f) both NKCF and NK-CIA activity are lost after 2 d at 37 degrees C. The NK-CIA-containing preparations are devoid of antiviral activity, and antiinterferon (anti-IFN) antibodies do not block the inhibitor activity of NK-CIA. The effect of NK-CIA on day 14 (early) colony-forming units of granulocytes and macrophages (CFU-GM) is synergistic with that of IFN-gamma, and this synergy is also evident on day 7 (late) CFU-GM growth. A combination of NK-CIA and IFN-gamma suppresses late CFU-GM, at concentrations of the two lymphokines that are completely ineffective when used independently. No synergy between NK-CIA and IFN-alpha or -beta was observed, due to a direct inhibitory effect of these two IFN types on late CFU-GM. Antibodies specific for tumor necrosis factor (TNF), but not those specific for lymphotoxins, inhibit both NK-CIA and NKCF activity in the NK cell-derived supernatant. Recombinant TNF, in the range of concentrations corresponding to that of the cytotoxic activity on L-929 cells present in supernatants, mediated both NKCF and NK-CIA activity.(ABSTRACT TRUNCATED AT 400 WORDS)
An arthritogenic lymphokine in the rat.
Authors: Helfgott S M , Dynesius-Trentham R , Brahn E , Trentham D E
Published: June 2004

A type II collagen-specific arthritogenic lymphokine has been identified in the rat. Arthritogenic factor (AF) is a 65 kD protein generated in vitro by T cells from rats with collagen arthritis, and it induces an erosive, proliferative synovitis when injected into the knee joint of syngeneic naive recipients. Complement does not appear to be required. These data identify a potential T cell-mediated effector mechanism in this model, and suggest that AF may function in other inflammatory synovial diseases.
Influenza virus subtype-specific cytotoxic T lymphocytes lyse target cells coated with a protein produced in E. coli.
Authors: Yamada A , Young J F , Ennis F A
Published: June 2004

We have tested the ability of the c13 protein, which is a hybrid protein of the first 81 amino acids of the viral nonstructural protein (NS1) and the HA2 subunit of viral hemagglutination produced in E. coli, to render target cells susceptible to the lytic activity of influenza virus-specific cytotoxic T lymphocytes (CTL). The results showed that P815 cells coated with c13 protein were lysed by PR8 virus-induced secondary CTL derived from BALB/c mice. Cold-target inhibition tests clearly demonstrated that c13 protein-coated P815 cells were recognized by an H1 subtype-specific CTL population. Furthermore, PR8 virus-induced CTL derived from C3H mice did not lyse c13 protein-coated P815 cells, suggesting that c13 protein was recognized by CTL in conjunction with H-2d products. These findings suggest that this protein interacts with the cellular plasma membrane and makes target cells recognizable by H-2-restricted, influenza virus subtype-specific CTL.
Truncated mu (mu') chains in murine IgM. Evidence that mu' chains lack variable regions.
Authors: Marks R , Bosma M J
Published: June 2004

Secreted IgM was shown to contain truncated mu (mu') chains with an apparent molecular mass of approximately 55 kD. The estimated percentage of IgM heavy (H) chains in the mu' form ranged from less than or equal to 1% in the case of one tumor IgM protein (104E) to greater than or equal to 30% in normal serum IgM. Serum mu' chains lacked antigenic determinants characteristic of immunoglobulin variable regions and showed a restricted isoelectric focusing pattern compared with that of conventional mu chains. Intracellular mu' chains were readily detected in bone marrow cells but not in spleen or lymph node cells; mu' chains were also detected in IgM-producing tumor cells and in a hybridoma cell line that deleted its productive mu allele. These results predict irregularities in IgM structure and recall an old controversy concerning the valence of IgM molecules.
Reevaluation of reserpine-induced suppression of contact sensitivity. Evidence that reserpine interferes with T lymphocyte function independently of an effect on mast cells.
Authors: Mekori Y A , Weitzman G L , Galli S J
Published: June 2004

It has been suggested that reserpine blocks expression of delayed hypersensitivity (DH) by depleting tissue mast cells of serotonin (5-HT), thereby preventing a T cell-dependent release of mast cell 5-HT necessary to localize and to amplify the DH response. However, reserpine blocks expression of DH in mast cell-deficient mice. We therefore decided to reevaluate the mechanism by which reserpine abrogates expression of cellular immunity, and investigated whether the drug might interfere with T cell activity in vitro or in vivo. At concentrations as low as 4 microM, reserpine profoundly suppressed baseline or antigen-augmented levels of [3H]thymidine incorporation by immune lymph node cells obtained from mice sensitized to the contactant oxazolone [I-LNC(Ox)]. This effect was observed both with I-LNC derived from normal mice and with I-LNC derived from congenitally mast cell-deficient W/Wv mice, cell preparations that lacked detectable mast cells, histamine, and 5-HT. Furthermore, treatment of I-LNC with reserpine (20 microM) for 1 h in vitro virtually abolished the ability of these cells to transfer CS to naive mice. This was not a cytolytic effect, as the viability of the I-LNC treated with reserpine was not affected, and washing of the reserpine-treated I-LNC before transfer fully restored their ability to orchestrate a CS response. The action of the drug was not mediated by an effect on mast cells, since the experiment could be performed using mast cell-deficient W/Wv mice as both donors and recipients of I-LNC. In addition, the effect was specific for the treated cells: mice that received reserpine-treated I-LNC(Ox) intravenously together with untreated I-LNC(DNFB) did not develop CS to Ox but responded normally to DNFB; and local intradermal injection of reserpine-treated I-LNC(Ox) which failed to transfer reactivity to Ox, did not interfere with the development of CS to DNFB at the same site. Finally, cotransfer experiments indicated that the effect of reserpine on the transfer of CS was not due to activation of suppressor cells. Our findings strongly suggest that whatever effects reserpine might have on immunologically nonspecific host cells, the drug's effects on sensitized T cells are sufficient to explain its ability to block cell-mediated immune responses in vivo.
Inhibition of complement-mediated opsonization and phagocytosis of Streptococcus pyogenes by D fragments of fibrinogen and fibrin bound to cell surface M protein.
Authors: Whitnack E , Beachey E H
Published: June 2004

The biological effects of the binding of fibrin(ogen) degradation products to M protein-bearing group A streptococci were investigated. Type 24 group A streptococci bind fibrinogen degradation products of the D family, but not fragment E. Binding appears to be mediated by M protein, since a large peptide of this molecule (pep M24) bound to fragments containing the terminal domains of the fibrinogen molecule (D, X, and Y), but not fragment E, and pep M24 inhibited the binding of digested fibrinogen to streptococcal cells. An M protein-binding site occurs on fragment D3 and, therefore, differs from several functional sites present on D1 but not D3, including the fibrin polymerization site, the two gamma chain crosslink sites, and the bindings sites for platelet fibrinogen receptor, staphylococcal clumping factor, and ionized calcium. Bound fibrinogen degradation products prevented deposition of C3 on the streptococcal cell surface, and, in consequence, prevented phagocytosis by neutrophils in nonimmune blood. The average affinity of D fragments for the streptococcal cell surface was approximately 30 times lower than that of native fibrinogen, and a terminal plasmic digest was approximately 50 times less potent in inhibiting opsonization by C3. However, physiologic concentrations of digested fibrinogen sufficed to inhibit opsonization and phagocytosis completely. Digests of crosslinked fibrin clot also inhibited opsonization, although slightly less effectively than did fibrinogen digests. The antiopsonic effect of fibrin(ogen) degradation products may be relevant to circumstances in which fibrin(ogen)olysis is occurring, e.g., exudation and suppuration.
Analyses of gonococcal H8 antigen. Surface location, inter- and intrastrain electrophoretic heterogeneity, and unusual two-dimensional electrophoretic characteristics.
Authors: Hitchcock P J , Hayes S F , Mayer L W , Shafer W M , Tessier S L
Published: June 2004

The H8 protein is a surface-exposed antigen that is found, among members of the Neisseria genus, primarily on pathogenic species. In this study, the surface exposure of H8 was reassessed by four techniques. Results of slide agglutination, indirect fluorescent antibody binding, absorption of sera with whole gonococci, and immune electron microscopy all confirmed the presence of H8 in the outer membrane. The degree to which protein A-gold-labeled monoclonal antibodies bound to H8 was marked, and suggested that this antigen was present in abundant amounts in the outer membrane. Also in this study, the electrophoretic heterogeneity of this common surface antigen was examined. Because H8 stains poorly, electrophoretic mobility was assessed using polyclonal antibodies and a monoclonal antibody that recognizes a common H8 epitope. H8 was analyzed with respect to protein I, lipopolysaccharide (LPS), and pilus and opacity phenotypic variation; results confirmed that heterogeneity of Mr was the rule among strains (21 were examined), however, the variability in Mr was independent of protein I or LPS Mr. In one strain (FA1090), the heterogeneity of H8 was examined among 10 piliation/opacity variants; the H8 (and LPS) Mr was identical in all variants; similar data were generated in strains JS3 and JS1. The electrophoretic mobility of H8 was altered in serum-resistant and neutrophil enzyme-resistant gonococci compared to the sensitive gonococci. Some of the unusual electrophoretic migration characteristics of the antigen were also examined. H8 formed a unique mushroom-shaped band in one-dimensional gels; in a two-dimensional electrophoresis system, the antigen migrated aberrantly, very similarly to LPS. Also seen in the two-dimensional electrophoresis profile were multimers of the H8 antigen; in strain JS3 (Mr 23,500), these migrated at 43,600, 86,000, and greater than 150,000. In other strains, the Mr of the multimers differed depending upon the Mr of the monomer. The two-dimensional migration characteristics (as measured by antigenicity) were completely destroyed by proteinase K digestion. Activity of H8 polyclonal antibodies to the antigens in two-dimensional gels was completely removed by adsorption of formalin-fixed whole cells, but was not affected by adsorption with LPS. These electrophoretic characteristics may reflect the close association of some nonprotein constituent, perhaps lipid or carbohydrate or both.
A naturally occurring bone marrow-chimeric primate. II. Environment dictates restriction on cytolytic T lymphocyte-target cell interactions.
Authors: Picus J , Holley K , Aldrich W R , Griffin J D , Letvin N L
Published: June 2004

Restriction on cytolytic T lymphocyte (CTL)-target cell-interactions are studied in the primate S. oedipus, a naturally occurring A + B----A bone marrow-chimeric species. We show that the T cell, B cell, and myelomonocytic progenitor cell populations are chimeric in this species. We selected animals for study that are populated by fully major histocompatibility complex (MHC)-disparate hematopoietic cell populations, using a functional assay system. We then developed an in vitro system for analyzing at the clonal level the genetic restrictions on the trinitrophenyl-specific CTL-target cell interactions of this species. In this system, we have shown that tolerance to foreign MHC determinants was not, of itself, sufficient to facilitate the generation of CTL specific for target cells expressing those foreign MHC determinants. Rather, a marked preference for the expansion of CTL clones with a restriction for target cells bearing the host animals' MHC determinants was seen. Hematopoietically derived cells did not affect the repertoire of these T lymphocytes. These studies represent the first demonstration of the phenomenon of an environment dictating interactional restrictions on CTL in a naturally occurring bone marrow-chimeric animal. This is also the first demonstration of the profound influence of the environment on the repertoire of the T lymphocyte in a primate species.
bcr Rearrangement without juxtaposition of c-abl in chronic myelocytic leukemia.
Authors: Bartram C R
Published: June 2004

Southern blot analysis detected a bcr gene rearrangement within leukemic cells of a Philadelphia chromosome-negative chronic myelocytic leukemia (CML) patient that led to transcription of a novel 7.3 kb bcr RNA species. Participation of the c-abl oncogene in this genomic recombination could be ruled out by in situ hybridization studies and Northern blot analysis.
Long‐Term Results of a Phase II Trial of Induction Chemotherapy with Uracil‐Ftegafur (UFT), Vinorelbine, and Cisplatin (UFTVP) followed by Radiotherapy Concomitant with UFT and Carboplatin (RT/UFTJ) in a Primary Site Preservation Setting for Resectable Locally Advanced Squamous Cell Carcinoma of Larynx and Hypopharynx
Authors: Rivera Fernando , Vega‐Villegas Maria E. , López‐Brea Marta F. , García‐Castaño Almudena , de Juan Ana , Collado Antonio , Galdós Piedad , Rubio Antonio , del Valle Adolfo , Rama Julio , Sanz‐Ortiz Jaime
Published: June 2004

Objective: We present long‐term results of a phase II trial of induction chemotherapy (IC) with uracilftegafur (UFT) 200 mg/m2 orally days 1 to 21, vinorelbine 25 mg/m2 intravenously (IV) days 1 and 8, and cisplatin 100 mg/m2 IV day 1 (UFTVP) each for 21 days for 4 courses, followed by radiotherapy concomitant with UFT 100 mg/m2 orally daily and carboplatin (area under the curve [AUC] = 0.5 IV weekly) (RT/ UFTJ), without surgery to the primary site if response, in patients (pts) with resectable locally advanced squamous cell carcinoma of the larynx and hypopharynx. The primary endpoint was clinical complete response (CR) to induction UFTVP, and secondary endpoints were long‐term overall survival (OS) and survival with primary site preservation (SPP).

Results: Between 1994 and 1997, 37 pts were included. CR to IC was 54% (95% confidence interval [CI] 43–65%). Main toxicity of UFTVP was G 3,4 neutropenia (73% of pts, 16% developed febrile neutropenia). After IC, primary site was treated with RT in 29 pts: 20 of them received RT/UFTJ (main toxicity mucositis G 3,4 70%). No pt died during treatment. Actuarial 5‐year OS and SPP were 57% and 37%, respectively.

Conclusions: This approach has significant activity and acceptable toxicity for achieving promising long‐term OS and SPP and deserves further investigation.
Intralingual Injection of Particulate Fascia for Tongue Paralysis
Authors: Burres Steven
Published: June 2004

This article reports for the first time in the medical literature an intralingual injection for the treatment of tongue paralysis. Hemiatrophy of the tongue produces a disabling problem of dysarthria and dysphagia because of discoordinated tongue movement, poor contact pressure, and areas of dead space. If a reversible neurologic etiology is not found, the patient may benefit from speech therapy, although recovery is often incomplete. In this case report, repeat injections of 80 mg of 0.5 mm preserved particulate fascia (Fascian®) into the paralyzed half‐tongue improved lingual symmetry and the patient's overall control of the tongue.
Spastic Diplegia and Other Motor Disturbances in Infants Receiving Interferon‐Alpha
Authors: Michaud André‐Paul , Bauman Nancy M. , Burke Diane K. , Manaligod José M. , Smith Richard J. H.
Published: June 2004

Objective: To determine how frequently the use of ‐interferon (‐IFN) is associated with the development of spastic diplegia.

Study Design and Methods: Meta‐analysis of 600 English manuscripts published January 1991 to June 2002 reporting ‐IFN use in infants/children. We identified 3,113 children 18 years of age or younger and an estimated 3,055 children 12 years of age or younger who received ‐IFN therapy. Sixty‐nine percent were treated for chronic hepatitis and 14% for vascular neoplasms.

Outcome Measure: Neurologic examination to confirm spastic diplegia or a motor developmental disturbance other than spastic diplegia such as hyperactive deep tendon reflexes, gait disturbances, or impaired fine motor control.

Results: Including our index case, 11 of 441 children with vascular lesions developed spastic diplegia and an additional 16 of 441 developed a motor developmental disturbance. All of these children were less than 1 year of age at initiation of therapy. Mean age of initiation and duration of ‐IFN therapy were not significantly different between groups (P > .05); however, motor developmental disturbances improved with cessation of therapy, whereas spastic diplegia did not. No child receiving treatment for chronic hepatitis developed neurologic complications; however, only 49 children were less than 1 year of age at initiation of therapy.

Conclusion: ‐IFN should not be used in infants under 1 year of age unless life‐threatening conditions do not respond to any other form of treatment. If ‐IFN must be used, children should have monthly neurologic examinations. If a motor developmental disturbance is detected and ‐IFN therapy can be discontinued, it should be.
Role of Local Immunoglobulin E Production in the Pathophysiology of Noninvasive Fungal Sinusitis
Authors: Collins Melanie , Nair Salil , Smith William , Kette Frank , Gillis David , Wormald Peter John
Published: June 2004

Objectives/Hypothesis: Immunoglobulin (Ig)E‐mediated hypersensitivity to fungi has been postulated to explain allergic fungal sinusitis (AFS). Not all patients suspected to have AFS demonstrate systemic evidence of allergy. Locally produced IgE might explain those patients with no systemic evidence of allergy but clinical features of AFS. The aim was to determine whether fungal‐specific IgE could be demonstrated in sinus mucin in patients with eosinophilic mucin rhino‐sinusitis.

Study Design: A prospective study was undertaken in a tertiary rhinology practice in Adelaide, South Australia.

Methods: Eighty‐six consecutive patients with nasal polyposis and thick, colored macroscopically “fungal‐like” sinus mucin at time of surgery for chronic sinusitis were entered in the study. The sinus mucin was liquefied and underwent testing for fungal‐specific IgE (Pharmacia UniCAP) and fungal culture. Serum fungal‐specific and total IgE, eosinophil count, C‐reactive protein (CRP), and eosinophilic cationic protein (ECP) were measured.

Results: Fifty‐six (65%) patients were fungal culture positive, and 37% had a detectable fungal‐specific IgE in sinus mucin. Data were available to classify 81 patients: AFS = 24 (30%), AFS‐like = 6 (7%), nonallergic eosinophilic fungal sinusitis = 32 (40%), nonallergic, nonfungal eosinophilic sinusitis = 19 (23%). Patients with AFS were significantly more likely to have fungal‐specific IgE in sinus mucin (17/24, 71%, P = .02). In all fungal culture‐positive patients, positive mucin fungal‐specific IgE was significantly associated with systemic fungal allergy (P = .005), but a raised total serum IgE was not. Six (19%) of the 32 patients with positive fungal cultures but negative serum fungal‐specific IgE had a positive mucin fungal‐specific IgE, suggesting that they may be reclassified as AFS. The mean ECP and total IgE were raised most significantly in the AFS subgroup.

Conclusions: This is the first study to show that fungal‐specific IgE may be demonstrated in sinus mucin. It was significantly associated with systemic fungal allergy and may play a role in a minority of fungal sinusitis patients in the absence of systemic fungal allergy.
Structural alignment of proteins by a novel TOPOFIT method, as a superimposition of common volumes at a topomax point
Authors: Ilyin Valentin A. , Abyzov Alexej , Leslin Chesley M.
Published: June 2004

Similarity of protein structures has been analyzed using three‐dimensional Delaunay triangulation patterns derived from the backbone representation. It has been found that structurally related proteins have a common spatial invariant part, a set of tetrahedrons, mathematically described as a common spatial subgraph volume of the three‐dimensional contact graph derived from Delaunay tessellation (DT). Based on this property of protein structures, we present a novel common volume superimposition (TOPOFIT) method to produce structural alignments. Structural alignments usually evaluated by a number of equivalent (aligned) positions (Ne) with corresponding root mean square deviation (RMSD). The superimposition of the DT patterns allows one to uniquely identify a maximal common number of equivalent residues in the structural alignment. In other words, TOPOFIT identifies a feature point on the RMSD Ne curve, a topomax point, until which the topologies of two structures correspond to each other, including backbone and interresidue contacts, whereas the growing number of mismatches between the DT patterns occurs at larger RMSD (Ne) after the topomax point. It has been found that the topomax point is present in all alignments from different protein structural classes; therefore, the TOPOFIT method identifies common, invariant structural parts between proteins. The alignments produced by the TOPOFIT method have a good correlation with alignments produced by other current methods. This novel method opens new opportunities for the comparative analysis of protein structures and for more detailed studies on understanding the molecular principles of tertiary structure organization and functionality. The TOPOFIT method also helps to detect conformational changes, topological differences in variable parts, which are particularly important for studies of variations in active/ binding sites and protein classification.
Solubilization and delivery by GroEL of megadalton complexes of the λ holin
Authors: Deaton John , Savva Christos G. , Sun Jingchuan , Holzenburg Andreas , Berry Joel , Young Ry
Published: June 2004

GroEL can solubilize membrane proteins by binding them in its hydrophobic cavity when detergent is removed by dialysis. The best‐studied example is bacteriorhodopsin, which can bind in the GroEL chaperonin at two molecules per tetradecamer. Applying this approach to the holin and antiholin proteins of phage λ, we find that both proteins are solubilized by GroEL, in an ATP‐sensitive mode, but to vastly different extents. The antiholin product, S107, saturates the chaperonin at six molecules per tetradecameric complex, whereas the holin, S105, which is missing the two N‐terminal residues of S107, forms a hyper‐solubilization complex with up to 350 holin molecules per GroEL, or approximately 4 MDa of protein per 0.8 MDa tetradecamer. Gel filtration chromatography and immunoprecipitation experiments confirmed the existence of complexes of the predicted masses for both S105 and S107 solubilization. For S105, negatively stained electron microscopic images show structures consistent with protein shells of the holin assembled around the chaperonin tetradecamer. Importantly, S105 can be delivered rapidly and efficiently to artificial liposomes from these complexes. In these delivery experiments, the holin exhibits efficient membrane‐permeabilizing activity. The S107 antiholin can block formation of the hypersolubilization complexes, suggesting that their formation is related to an oligomerization step intrinsic to holin function.
Behind the Numbers: Talking Politics with Foreign‐born Chinese Americans
Authors: Lien Pei‐te
Published: June 2004

This paper discusses results of in‐depth follow‐up interviews conducted with selected individuals of Chinese descent residing in Los Angeles and San Francisco who were previously chosen at random to participate in the 2000 and 2001 Pilot National Asian American Political Survey. A total of 15 male and female informants who had migrated from Taiwan, mainland China, and Hong Kong were interviewed in Mandarin Chinese. They were asked to compare the performance of the US Government with that of the government in their respective ethnic homeland. They were also asked to explain their reasons for supporting a certain US political party, ideology, and type of candidate. In addition, they commented on the state of political participation or the lack of it among Chinese Americans. Finally, they explained the complexity of their ethnic self‐identification and experiences of racial discrimination. Their responses were interpreted within the context of the historical formation of the Chinese American community as well as the summary results of the mass opinion survey. The results help dispel myths about Chinese Americans being politically indifferent and irrational. They help illuminate the possible relationships among ethnic identity, homeland politics, and political participation in the host land. They also provide exciting insights into improving the survey instrument for a majority immigrant and non‐Anglophone population.
Phylogeny of Australasian venomous snakes (Colubroidea, Elapidae, Hydrophiinae) based on phenotypic and molecular evidence
Authors: Scanlon John D. , Lee Michael S. Y.
Published: June 2004

Scanlon, John D. & Lee, Michael S. Y. (2004). Phylogeny of Australasian venomous snakes (Colubroidea, Elapidae, Hydrophiinae) based on phenotypic and molecular evidence. — Zoologica Scripta, 33, 335–366.

Phylogenetic relationships among Hydrophiinae (Australasian and marine elapid snakes) are inferred using 87 characters from external, skeletal, hemipenial and internal anatomy, ecology, and chromosomes as well as available sequences of two mitochondrial genes (cytochrome b and 16S rRNA). Parsimony analysis of the combined data retrieves many widely accepted clades; while observed bootstrap or branch (Bremer) support for these is often weak, most have never been corroborated previously by a rigorous numerical analysis. Sea kraits (Laticauda) and Solomon Islands elapids are basal to the remaining hydrophiines (Australian terrestrial forms and hydrophiin sea snakes). The latter clade includes three main lineages: a large‐bodied oviparous lineage, a small‐bodied oviparous lineage, and a viviparous lineage (which also includes the hydrophiin sea snakes, strongly reaffirmed as monophyletic). While the Solomons retain a relictual fauna, New Guinea has less endemism and has been invaded multiple times by Australian lineages, so there is no clear ‘stepping stone’ pattern supporting a northern (Asian, rather than Gondwanan) biogeographical origin.
Phylogeny of Recent Canidae (Mammalia, Carnivora): relative reliability and utility of morphological and molecular datasets
Authors: Zrzavý Jan , ŘIčánková Věra
Published: June 2004

Zrzavý, J. & Řičánková, V. (2004). Phylogeny of Recent Canidae (Mammalia, Carnivora): relative reliability and utility of morphological and molecular datasets. — Zoologica Scripta, 33, 311–333.

Phylogenetic relationships within the Canidae are examined, based on three genes (cytb, COI, COII) and 188 morphological, developmental, behavioural and cytogenetic characters. Both separate and combined phylogenetic analyses were performed. To inspect the phylogenetic ‘behaviour’ of individual taxa, basic phylogenetic analysis was followed by experimental cladistic analyses based on different data‐partition combinations and taxon‐removal analyses. The following phylogeny of the Recent Canidae is preferred: (1) Urocyon is the most basal canid; (2) Vulpes is a monophyletic genus (including Fennecus and Alopex); (3) the doglike canids (DC) form a clade (=Dusicyon + Pseudalopex + Lycalopex + Cerdocyon + Atelocynus + Chrysocyon + Speothos + Lycaon + Cuon + Canis), split into two subclades, South American and Afro‐Holarctic, with uncertain position of the Chrysocyon + Speothos subclade; (4) Canis is paraphyletic due to the position of Lycaon and Cuon. Otocyon and Nyctereutes are the most problematic canid genera, causing an unresolved branching pattern of Otocyon, Vulpes, Nyctereutes and DC clades. Reclassification of the two basal species of ‘Canis’ into separate genera is proposed (Schaeffia for ‘C.’ adustus, Lupulella for ‘C.’ mesomelas). Although the morphological dataset ranked poorly in both separate and simultaneous analyses (measured by number of minimum‐length topologies, relative number of resolved nodes in the strict consensus of all minimum‐length topologies, consistency and retention indices, nodal dataset influence, and number of extra steps required by the data partition to reach the topology of the combined tree), the morphological synapomorphies represent nearly one quarter of all synapomorphies in the combined tree. Among the hidden morphological support of the combined tree the developmental and behavioural characters are conspicuously abundant.
The Genus Lechenaultia
Authors: Morrison David , George Alex
Published: June 2004

Summary.  Lechenaultia is a genus of about 30 species in the largely Australian family Goodeniaceae. Most are small shrubs but some are annuals. They have short, fine leaves and terminal sprays of hand‐like flowers with usually winged lobes. The range of flower colour is remarkable and includes shades of red, blue, yellow, white and green.
Plate 492. Lechenaultia acutiloba Goodeniaceae
Authors: Morrison David , George Alex
Published: June 2004

Summary.  Lechenaultia acutiloba Benth. (Goodeniaceae) is a rare, greenish‐yellow‐flowered species of compact form, unknown in cultivation in Britain.
Plate 496. Lechenaultia striata Goodeniaceae
Authors: Morrison David , George Alex
Published: June 2004

Summary.  Lechenaultia striata F. Muell. (Goodeniaceae) is a desert species of upright habit, with pale blue to creamy white flowers. It is unknown in cultivation outside Australia.
A case of fatal systemic toxoplasmosis in a cat being treated with cyclosporin A for feline atopy
Authors: LAST ROBERT D. , SUZUKI YASUHIRO , MANNING THOMAS , LINDSAY DAVID , GALIPEAU LAURA , WHITBREAD TREVOR J.
Published: June 2004

Abstract Acute systemic toxoplasmosis was diagnosed in a 4–5‐year‐old, male, Domestic Short Hair cat, which had been on cyclosporine A immunomodulatory therapy for feline atopy, over an 8‐month period. Cyclosporin A (CsA) has shown promising results as a immunosuppresive agent in the cat for the treatment of eosinophilic plaque and granulomas, allergic cervico‐facial pruritus, feline atopy and other immune‐mediated dermatoses. However, inhibition of T‐lymphocyte function by CsA is believed to have predisposed this cat to the development of a newly acquired, acuteToxoplasma gondiiinfection, as characterized by severe hepatic and pancreatic pathology in conjunction with the heavy parasite load demonstrated on immunohistochemical (IHC) stains forT. gondii. Cats on CsA therapy appear to be at risk of developing fatal systemic toxoplasmosis.
Identification of a Common Structural Motif in the Disordered N‐Terminal Region of Bacterial Flagellins — Evidence for a New Class of Fibril‐Forming Peptides
Authors: Hakalehto Elias , Santa Harri , Vepsäläinen Jouko , Laatikainen Reino , Finne Jukka
Published: June 2004

Flagellin proteins lacking the N‐ or C‐terminus form polymers of reduced filament stability and straight morphology, in contrast to the coiled native flagella. In the present study, the N‐terminal amino acid sequence of flagellins of the anaerobic beer spoilage bacteria Pectinatus cerevisiiphilus and Pectinatus frisingiensis as well as Enterobacter aerogenes and Pseudomonas sp. were determined. Sequence similarity was revealed between these and the N‐termini of all known eubacterial flagellins. Synthetic peptides corresponding to the first 15 amino acid residues of the flagellins of Pectinatus, Campylobacter jejuni, E. aerogenes or Proteus mirabilis flagellins had a spontaneous tendency under physiological conditions to form 4–6 nm broad, 1–2 μm long fibrillar structures that had a tendency to form clusters. In contrast, the Pectinatus peptide missing residues 1–3 did not form fibrils. The peptide missing residues 13–15 formed fibrils less easily, and the peptide missing residues 11–15 formed fibrils almost without clustering. In electron micrographs, the fibrillisation of the bacterial flagellar peptides resembled that of β‐amyloid and prion peptides. 1H‐NMR and infrared spectroscopy studies with homology analysis indicate that although the flagellar N‐terminal peptides are flexible with many conformational minima, they have a significant tendency to form β‐type structures and a loop in the middle of the peptide. The hydrophobic character of the N‐terminus together with the property of forming a conserved β‐strand–loop–β‐strand motif may be related to a mechanism involved in attaining the proper morphology and stability of the flagellar filament, by providing a device for facilitating the attachment of the flagellin monomers to each other. The flagellar peptides represent a new class of fibril‐forming peptides.
Fourier‐Transform Infrared Spectroscopic Studies on the Coordination of the Side‐Chain COO− Groups to Ca2+ in Equine Lysozyme
Authors: Mizuguchi Mineyuki , Nara Masayuki , Ke Yue , Kawano Keiichi , Hiraoki Toshifumi , Nitta Katsutoshi
Published: June 2004

Interactions between Ca2+ and the Asp side chains in the Ca2+‐binding site of equine lysozyme were investigated by Fourier‐transform infrared (FT‐IR) spectroscopy. In the spectrum of equine lysozyme, the intensities of the bands at about 1595 cm−1 and 1578 cm−1 in the region of the COO− antisymmetric stretches increased upon Ca2+ binding. In the region of the COO− symmetric stretches, the loss of intensity at about 1388 cm−1 and gains of intensities at about 1423 cm−1 and 1403 cm−1 were observed due to Ca2+ binding to equine lysozyme. The spectral changes for equine lysozyme indicate that the COO− groups of Asp85, Asp90 and Asp91 in the Ca2+‐binding site coordinate to Ca2+ in the pseudo‐bridging mode, where divalent metal cation is bound to one of the two oxygens in the COO− group and a water molecule is hydrogen bonded to the other oxygen. The results presented here provide further evidence for a high degree of similarity between Ca2+‐binding lysozyme and α‐lactalbumin. The effects of Ca2+ binding on the main‐chain conformation of equine lysozyme were compared with those of bovine α‐lactalbumin and hen egg‐white lysozyme.