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Biomedical subjects

C Hauser

Publications and source records attributed to C Hauser.

At least 127 records · Page 7Linked to original sources

A syndrome characterized by nodular eosinophilic infiltration of the skin and immunoglobulin isotype imbalance.

A 9-year-old boy had recurrent acute, plaquelike, nodular infiltrations with overlying vesicles and bullae of the face and right hand. Histologically, the lesions consisted of a perivascular and periadnexal lymphohistiocytic infiltrate with many eosinophils. The lesions responded to dapsone therapy. Laboratory studies revealed blood eosinophilia, hyperimmunoglobulinemias E and G4, and hypoimmunoglobulinemias M and G1-3, which normalized after treatment. The patient's immune deviation is consistent with a transient imbalance of lymphokine production in helper T cells.

Child↗

Complement consumption in a patient with necrobiotic xanthogranuloma and paraproteinemia.

Necrobiotic xanthogranuloma and paraproteinemia have been reported to be associated with acquired deficiency of the early components of the classic pathway of complement. We describe a patient in whom activation of complement was suggested by a high level of C3d, an accelerated catabolism of C1q, and a rapid consumption of C4 after an intravenous infusion of fresh-frozen plasma. This infusion was followed by an episode of pulmonary edema. Patients with complement deficiency or depletion should be monitored closely while receiving plasma, to avoid this potential complication.

Complement C1q↗

Mononuclear cell-bound CD23 is elevated in both atopic dermatitis and psoriasis.

As patients with atopic dermatitis (AD) frequently have elevated serum IgE levels, the relation of this disease to CD23/Fc epsilon RII, a low affinity Fc receptor for IgE, and its soluble forms, sCD23, was studied. We examined the expression of CD23 on peripheral blood mononuclear cells (PBMC) as well as the serum IgE and sCD23 levels in 33 patients with AD and in 9 patients with psoriasis in comparison with 10 healthy donors. In AD patients, the numbers of CD23+ unfractionated PBMC and CD23+ small adherent cells were significantly elevated (P less than 0.05, resp. P less than 0.005). In psoriatic patients however, CD23 was also significantly elevated on PBMC (P less than 0.05) and on small adherent cells (P less than 0.05). There was no significant difference in the frequencies of CD23+ cells between AD and psoriasis patients. In all donors, CD23 could be detected only on B cells, but not on monocytes/macrophages. In AD patients who were examined twice, an increase or decrease of the clinical AD score was always accompanied by an increase or decrease, resp., of cell-bound CD23. The serum sCD23 level was not significantly increased in either group of patients. Our results suggest that CD23 should be considered as a nonspecific marker for B cell activation in the context of inflammation and not as a specific marker for AD.

Adolescent↗

Soluble factor-independent stimulation of human B cell response by mouse thymoma cells. Cyclosporine A-resistant and -sensitive cell contact signals.

In a Th cell-dependent antibody response, the Th act on B cells partly via a helper activity that is cell contact-dependent and cyclosporine A (CsA)-resistant. This activity seems to be required to induce responsiveness of the B cells toward T cell-derived soluble factors (cytokines) generally believed to be essential for B cell proliferation as well as for Ig secretion. In our study, we have investigated a system in which human B cells are stimulated by mutant EL-4 thymoma cells of mouse origin. It was found that human B cells proliferate and secrete Ig (either 1) in the presence of EL-4 cells plus human T cell supernatant (T-SUP), or 2) in the presence of EL-4 cells alone which have been induced with PMA or IL-1. The first situation conformed to the known synergy between CsA-resistant Th signal and cytokines. However, the B response due to PMA-induced EL-4 cells was special. The PMA-inducible helper activity was CsA-sensitive at the same CsA concentration that inhibited IL-2 secretion of EL-4 cells, but the murine factors in EL-4 supernatant had no effect on human B cells; the helper effect did not occur across a semipermeable membrane. Any contribution of soluble factors from contaminating human T cells was ruled out by adding single human B cells by flow microfluorimetry to cultures with EL-4 cells and PMA. Such B cells generated clonal IgM, IgG, and/or IgA responses. CsA, thus, interfered with some cell contact-mediated signal. However, CsA did not reduce the amount of LFA-1 molecules on EL-4 cells. In conclusion, EL-4 cells can induce proliferation and differentiation of human B cells in a soluble factor-independent manner, via CsA-resistant and CsA-sensitive helper activities. This may represent an alternative pathway of B cell activation.

Animals↗

A patient with features of both Bardet-Biedl and Alström syndromes.

We describe a 30-year-old patient with acanthosis nigricans, diabetes mellitus with insulin resistance, hypogonadotropic hypogonadism, pigmentary degeneration of the retina and cerebellar, pyramidal and posterior columnar involvement. He had normal mental function, normal hearing and no hexadactyly. The patient had symptoms of both Bardet-Biedl and Alström syndromes, but did not manifest all the main features of either syndrome. This suggests either that the Bardet-Biedl, Alström, Laurence-Moon syndromes (including the variant described by Edwards) have a highly variable expression or that our case is a new variant within this group of syndromes.

Acanthosis Nigricans↗

The expression of the Autographa californica nuclear polyhedrosis virus genome in insect cells.

This report presents a synopsis of recently published work in our laboratory on the molecular biology of the insect baculovirus Autographa californica nuclear polyhedrosis virus (AcNPV). The following studies have been summarized. (1) On the mode of transcription of the AcNPV genome in insect cells. (2) Translation of proteins encoded in the 81.2 to 85.0 map unit segment of AcNPV. (3) Inserts of insect cell DNA in the AcNPV genome. (4) Expression of influenza (fowl plague) virus haemagglutinin in Spodoptera frugiperda insect cells, and successful immunization of chickens. (5) Synthesis of the influenza virus haemagglutinin in insect larvae by recombinant AcNPV. This insect virus system will continue to serve as a model for research on the molecular biology of insects. Moreover, the baculovirus system has been recognized as a very efficient and safe eukaryotic expression vector.

Animals↗

Cultured epidermal Langerhans cells activate effector T cells for contact sensitivity.

To investigate whether Langerhans cells are capable of inducing contact sensitivity effector T cells, we incubated purified T cells from naive mice with syngeneic cultured trinitrophenyl-modified Langerhans cells for 4-5 d. The cells were then expanded in interleukin-2 and fresh medium for another 6-9 d and injected intravenously into naive syngeneic recipient mice. After the ears of recipient mice were painted with 1% trinitrochlorobenzene, we observed an ear-swelling response peaking at 24-48 h. The ear-swelling response was hapten specific. CD8- but not CD4-depleted T cells mediated strong contact sensitivity. Systemic adoptive transfer into nude mice also lead to a hapten-specific delayed ear-swelling response. However, this response was less protracted than in euthymic animals, suggesting the participation of the recipient (non-immunized) T cells in the ear-swelling response of the euthymic mice. Lymphokine analysis of in vitro primed and restimulated T cells revealed predominant production of interleukin-2 but little or no interleukin-4. These in vitro primed cells therefore resemble type 1 or inflammatory T helper cell clones.

Animals↗

Generation and characterization of T-helper cells by primary in vitro sensitization using Langerhans cells.

We have utilized cultured Langerhans cells to activate and expand hapten- and protein-specific T-helper cells from nonsensitized mice. The generation of these lines was strongly dependent on eliminating all autologously reacting cells from the responder T-cell population. Primary in vitro sensitization was not uniquely induced with cultured Langerhans cells as splenic dendritic cells could subserve the same function. Despite its ability to induce strong allogeneic T-cell responses as well as hapten-specific secondary responses, M12c cells, a class II-bearing B-cell lymphoma line, could not activate hapten-specific T-helper cells in vitro. After primary or secondary in vitro stimulation, the T-helper cells which are generated secrete IL-2 and are able to adoptively transfer hapten-specific contact sensitivity, thus stimulating Type-1 T-helper cells. The T-helper cell lines which were generated after repeated cycles of stimulation stimulated type-2 T-helper cells in that they produced IL-4 and depended on this cytokine for autocrine growth. As well, when cultured with syngeneic, hapten-modified, small resting B cells, these T-helper cells caused specific IgE production. Thus, the studies reported herein demonstrate that it is possible to activate and expand T-helper cells with desired specificity from nonsensitized animals in vitro. Previous studies have demonstrated that expansion and adoptive transfer of effector T cells with specificity for tumor-associated antigens may be useful in the control of certain tumors; T-helper cells generated by in vitro sensitization should also be useful in adoptive immunotherapy.

Animals↗

Drosophila melanogaster strand transferase. A protein that forms heteroduplex DNA in the absence of both ATP and single-strand DNA binding protein.

The purification of a Drosophila strand transfer protein is described, which involves Bio-Rex 70, Superose 6, Mono S, and single-stranded DNA-agarose chromatography. A 105,000-dalton polypeptide copurifies with the strand transfer activity on the last two column steps. The strand transferase carries out strand transfer at an unusually low protein:single-stranded DNA ratio and requires neither a nucleotide cofactor nor exogenous single-strand DNA binding protein to form heteroduplex DNA. Biochemical analysis of the reaction products has established that one strand of the DNA duplex is displaced during the reaction. Several properties, including the kinetics and stoichiometry of strand transfer, differentiate this activity from previously characterized strand transferases.

Adenosine Triphosphate↗

T helper cells grown with hapten-modified cultured Langerhans' cells produce interleukin 4 and stimulate IgE production by B cells.

Hapten-specific CD4+ T helper (Th) lines generated by repeated stimulation with hapten-modified, cultured Langerhans' cells (cLC) release interleukin (IL 4) (B cell stimulatory factor 1) but not detectable IL 2 into the culture media. The growth of Th cells in response to hapten-modified cLC was inhibited by an anti-IL 4 monoclonal antibody (mAb) but not by mAb to either IL 2 or the p55 chain of the IL 2 receptor. Furthermore, these cells could be stimulated to proliferate by concanavalin A and IL 1. These results indicate that IL 4 is the autocrine growth factor for these Th lines and that IL 1 plays a critical role in their growth. The Th cells exhibited 1,500-10,000 high-affinity IL 4 receptors cell. When cultured with syngeneic, hapten-modified, small resting B cells, Th cells caused specific IgE production of up to 20 ng/10(4) B cells. Thus, IL 4 producing Th lines appear to result from their selective stimulation by cLC, suggesting that T cell responses elicited in this way profoundly influenced the B cell isotype pattern.

Animals↗

Characterization of primary T helper cell activation and T helper cell lines stimulated by hapten-modified, cultured Langerhans cells.

It has recently been shown that hapten-modified cultured Langerhans cells are able to activate small resting syngeneic L3T4+ T helper cells from nonsensitized animals. Repeated stimulation of these T cells with hapten-modified cultured Langerhans cells leads to the establishment of L3T4+ hapten-specific interleukin-4-producing T-cell lines. Here we report on further characteristics of primary hapten-dependent activation of L3T4+ T cells and of T-cell lines derived from them. Dendritic cell-enriched spleen cells were as able as Langerhans cells to activate nonsensitized T helper cells after hapten modification. However, M12c, a major histocompatibility complex class II-positive B-cell line that was able to activate small, resting, allogeneic L3T4+ T cells was not able to stimulate syngeneic T helper cells after hapten modification. Thy1+ dendritic epidermal cells did not significantly affect the magnitude of primary T helper cell proliferation induced by cultured Langerhans cells. Restimulation of in vitro primed T helper cells with hapten-modified cultured Langerhans cells revealed the presence, within the primed T helper cell population, of activated cells with specificity to an unrelated hapten, suggesting that, in hapten-dependent T helper cell activation, hapten-nonspecific cells are activated along with those that are hapten specific. Restimulation of a hapten-specific long-term T helper cell subline using different antigen-presenting cell types demonstrates that factors other than major histocompatibility complex class II density or tissue derivation of the antigen-presenting cell play a role in the activation of T cells in vitro. Finally, we demonstrate that in vitro generated hapten-specific T helper cell lines may not show strict major histocompatibility complex restriction.

Animals↗

Synthesis of biologically active influenza virus hemagglutinin in insect larvae.

The hemagglutinin of influenza (fowl plague) virus was expressed in larvae of Heliothis virescens by using recombinant Autographa californica nuclear polyhedrosis virus (AcNPV) as a vector. Animals were infected with the recombinant virus either by parenteral injection or by feeding. For oral uptake, recombinant virus occluded in polyhedra obtained from cultured Spodoptera frugiperda cells after coinfection with authentic AcNPV was used. Immunohistological analyses of infected animals revealed that the hemagglutinin was expressed only in those tissues that are also permissive for the replication of authentic AcNPV. These tissues included hypodermis, fat body, and tracheal matrix. After oral infection, hemagglutinin was also detected in individual gut cells. The amount of hemagglutinin synthesized in larvae after parenteral infection was 0.3% of the total protein, compared with 5% obtained in cultured insect cells. The hemagglutinin was transported to the cell surface and expressed in polarized cells only at the apical plasma membrane. It was processed by posttranslational proteolysis into the cleavage products HA1 and HA2. Oligosaccharides were attached by N-glycosidic linkages and were smaller than those found on hemagglutinin obtained from vertebrate cells. Hemagglutinin from larvae expressed receptor binding and cell fusion activities, but quantitation of the hemolytic capacity revealed that it was only about half as active as hemagglutinin from vertebrate or insect cell cultures. Chickens immunized with larval tissues containing hemagglutinin were protected from infection with fowl plague virus. These observations demonstrate that live insects are able to produce a recombinant membrane protein of vertebrate origin in biologically active form.

Administration, Oral↗

[Proteinuria in normal pregnancy and in EPH gestosis].

EPH-gestosis (pre-eclampsia-eclampsia) characterized by edema, proteinuria and hypertension occurs primarily in the nullipara, usually after the 20th gestational week. As in normal pregnancy there is striking change in both renal blood flow and glomerular filtration rate a slight increase in urinary protein secretion is not considered abnormal until it exceeds 300 mg/day. Abnormal proteinuria commonly accompanies pre-eclampsia and may be minimal, moderate or severe (even exceeding greater than 25 g/l). Proteinuria was typed mainly of nonselective glomerular origin by using the SDS-disc-electrophoresis. Additionally the clearance ratio of IgG to transferrin in all patients with abnormal proteinuria was evaluated. In none of the patients studied the ratio was less than 0.1 (highly selective). As severe proteinuria is associated with fetal growth retardation, preterm deliveries and prenatal mortality the quantitation and typing of early proteinuria is essential for considering patients who are at risk for developing EPH-gestosis.

Adolescent↗

Overproduction of the protein encoded by the maize transposable element Ac in insect cells by a baculovirus vector.

The polypeptide encoded in the Activator (Ac) element of Zea mays L. has been expressed in Spodoptera frugiperda insect cells using plasmids which carry the strong polyhedrin promoter of the baculovirus Autographa californica nuclear polyhedrosis virus (AcNPV). Recombinant AcNPVs with the Ac-cDNA integrated and under the control of the viral polyhedrin promoter have been isolated and their genomes have been partly characterized as to the location of the foreign DNA insert. Upon infection of S. frugiperda cells with the recombinant AcNPV, maize Ac element specific messenger RNAs, as well as a newly synthesized polypeptide with an apparent molecular weight of about 116 kDa, have been detected in extracts of recombinant infected cells. This polypeptide is absent from extracts of wild-type infected cells expressing the polyhedrin polypeptide which can be recognized by the presence of nuclear inclusion bodies. Recombinant infected cells lack this protein. The Ac specific polypeptide is detected by antisera, which have been raised against fusion proteins containing Ac sequences synthesized in Escherichia coli, both in immunoprecipitation and in Western blotting experiments. The Ac specific protein is a nuclear phosphoprotein and represents about 1%-2% of the newly synthesized protein.

Animals↗

Radiosensitive Down syndrome lymphoblastoid lines have normal ionizing-radiation-induced inhibition of DNA synthesis.

The extent of X-ray-induced inhibition of DNA synthesis was determined in radiosensitive lymphoblastoid lines from 3 patients with Down syndrome and 3 patients with ataxia telangiectasia (AT). Compared to 6 normal control lines, the 3 AT lines were abnormally resistant to X-ray-induced inhibition of DNA synthesis, while the 3 Down syndrome lines had normal inhibition. These results demonstrate that radiosensitive human cells can have normal X-ray-induced inhibition of DNA synthesis and provide new evidence for the dissociation of radiosensitivity from radioresistant DNA synthesis.

Ataxia Telangiectasia↗