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Biomedical subjects

H Spengler

Publications and source records attributed to H Spengler.

At least 19 recordsLinked to original sources

Release of histamine from human leukocytes by one preparation of IgG oligomers.

In preliminary experiments aimed at investigating the effect of covalently cross-linked human myeloma subclass proteins on histamine release from human leukocytes, we observed one preparation (designated here IgG-HR) made from pooled, purified immunoglobulin G, which consistently released histamine from these cells. Dimers and trimers, but not monomers isolated from columns of Sephadex G-200 and Ultrogel AcA22 following incubation of immunoglobulin G (Nordic Laboratories) with dimethyl suberimidate, released histamine from cells of all donors tested. In contrast, cells from the same donors showed variable responsiveness to dimers of IgE (prepared by similar techniques) or to anti-IgE. IgG-HR failed to release histamine from a "basophil-rich" mononuclear cell preparation depleted of most of the erythrocytes, platelets, neutrophils and eosinophils by centrifugation through a Ficoll-Hypaque cushion. The data suggest that IgG-HR was releasing histamine indirectly from basophils by first interacting with another cell. IgG oligomers prepared from different sources of pooled, purified IgG failed to release histamine. Although we did not have sufficient IgG-HR to adequately define this releasing activity, we feel that the data represent a potentially novel, if rare, mechanism of mediator release involving basophils and another cell.

Cross-Linking Reagents↗

Failure of covalently cross-linked human IgG myeloma subclass protein to release histamine from human leukocytes.

We have examined the ability of IgG subclass antibodies to release histamine from human leukocytes using covalently cross-linked oligomers of human myeloma proteins. Purified IgG1, G2, G3, G4, (or IgE) was incubated with dimethyl suberimidate to induce cross-linking. The resulting dimers, trimers, and higher molecular weight oligomers were isolated using gel filtration columns (Sephadex G200 and Ultrogel AcA 22) connected in tandem. None of the oligomers of IgG1, G2, G3, or G4 released histamine from leukocytes of donors whose basophils released histamine when challenged with IgE dimer. Furthermore, preincubation with subclass specific oligomers did not desensitize cells to challenge with IgE dimer or to anti-IgE. We conclude that, under our experimental conditions, oligomers of human IgG myeloma subclass antibodies do not trigger histamine release nor modulate IgE-mediated reactions.

Cells, Cultured↗

Effect of storage of penicillin-G solutions on sensitisation to penicillin-G after intravenous administration.

Intravenous administration of a total dose of more than 200 million IU of penicillin-G led to sensitisation of lymphocytes and formation of specific anti-penicilloyl antibodies of the IgG class. These effects were prevented when the penicillin solution used was freshly prepared and given as a bolus rather than as a slow infusion. The causative antigens seem to be related not to penicilloylated high molecular weight impurities in the penicillin preparations, but to the degradation and/or transformation products of penicillin-G that form when the drug is in solution even if only for a few hours, and not only at room temperature but also at 4 degrees C. Thus penicillin solutions should be freshly prepared and administered from vials containing less than 10 million IU so that bolus doses can be given.

Adult↗

Lymphocyte transformation by insulin and insulin-zinc suspensions.

The lymphocyte transformation response to the mitogen phytohaemagglutinin (PHA) was determined in 15 well controlled insulin-dependent diabetics (IDD) with a history of insulin allergy or an acute insulin allergy. There was no significant difference in the PHA response of IDD and normal subjects matched in respect of age and sex. The response of peripheral blood lymphocytes to insulin (Actrapid) and an insulin zinc suspension (Monotard) was also determined. Fifty-three percent of IDD gave a positive reaction to Actrapid. Monotard produced positive reactions both in IDD and normal subjects. In normal subjects, a close correlation between the stimulation indices of Monotard and PHA was found (r = 0 . 966) suggesting that these stimulations depend on a common parameter namely, the reactivity to mitogens.

Adolescent↗

Neutropenia after penicillins: toxic or immune-mediated?

Eight patients treated with a total of 220-550 million U penicillin-G developed neutropenia. These cases have been compared with eight patients receiving a similar dose of pencillin-G with no adverse reactions and with eight untreated subjects. All penicillin-treated patients showed raised levels of anti-IgG antibodies and lymphocyte culture stimulation indices. These values were highest in the neutropenia group. Both of the two tests significantly discriminated the three groups. Antineutrophil antibodies could be detected in four of seven neutropenic patients with a staphylococcal-slide-assay while indirect immunofluorescence and microcytotoxicity tests failed to reveal these antibodies. The literature dealing with neutropenias induced by penicillin-G and its congeners is reviewed. We conclude that (1) penicillin-G in doses exceeding a total of 200 million U frequently induces neutropenia, (2) an immune-mediated pathogenesis a highly probable, (3) neutropenia after penicillins is different from two hither-to accepted types of this side effect, (4) sufficiently high amounts of penicillin-G intravenously always induce sensitization against this drug.

Adolescent↗

[Drug fever caused by the antidepressive agent nomifensine (Alival)].

During 1979 4 patients were observed who developed short episodes of fever as high as 104 degrees F after oral intake of 25--100 mg nomifensine (Alival). In all four cases a clear fever spike was produced by reexposure to the drug. The reaction time was 4--6 hours. this drug-induced fever appeared initially 2--4 weeks after the commencement of Alival therapy. No other cause for the fever was identifiable. In one patient an allergic alveolitis was suspected to be a further reaction. In another patient a concomitant granulomatous hepatitis was possibly also due to this drug. It is probable that the febrile reactions have an allergic mechanism. Allergologic investigations have not yet been completed.

Aged↗

Flow-cytofluorometric determination of active and total rosettes.

A flow-cytofluorometric technique is described for determining active and total rosettes formed by sheep red blood cells with human peripheral blood lymphocytes. This technique correlates well with the microscopic determination of active rosettes, when these are defined as three or more erythrocytes per lymphocyte, and with the determination of total rosettes, when these are defined as four or more erythrocytes per lymphocyte. In the small group of tumor patients tested, the observed decrease in capacity to form active rosettes was found to be dependent on the individual sheep red blood cells used, while the levels of total rosettes were not affected by individual SRBC's and were not significantly different from those of normal blood donors. Flow-cytometry is a rapid, reproducible and objective technique, which permits better measurement than microscopy of total and active rosette levels in both normal donors and cancer patients.

Animals↗

Immunogenicity of p-phenetidine, 2-hydroxy-p-phenetidine and their protein conjugates in guinea pigs, rabbits and man.

Guinea pigs were sensitized by p-phenetidine (PT), 2-hydroxy-p-phenetidine (HPT) as well as by conjugates prepared by reacting PT and HPT with proteins in vitro. Sensitization was evaluated by delayed skin reactivity and in vitro antigen-induced lymphocyte proleferation. HPT and HPT-protein conjugates were found to be the most effective sensitizing agents. Reaginic antibodies could be raised in both guinea pigs and rabbits by immunizing with PT- and HPT-protein conjugates but not by PT and HPT alone: these PCA antibodies showed strong cross-reactivity and could be elicited equally well with either the PT- or HPT-protein derivatives. By contrast, no precipitating antibodies could be raised in either species even after repeated immunizations over a period of 4 months. Peripheral blood lymphocytes, from a few patients who gave a positive patch test with PT, could be stiumlated in vitro with phenacetin and to a lesser degree with PT and with a HPT-derivative of human serum albumin.

Aniline Compounds↗

Evaluation of genetic control of the immune response to penicillin in man.

HLA typing of 46 patients with demonstrated penicillin allergy did not show significant correlation of hypersensitivity to the penicilloyl group with any HLA antigens. On the other hand, lymphocytes from penicillin-sensitive patients generated nonspecific cytotoxic cells (e.g., cytotoxic for P 815 mastocytoma mouse cells or chicken red blood cells) when cultured in vitro together with penicillin. Under similar conditions, only some lymphocyte populations from nonpenicillin-sensitive normal individuals showed cytotoxicity. Although family studies are required to demonstrate that differences in the generation of cytotoxic cells by penicillin in nonsensitive populations are due to genetic factors, it is obvious that attempts to achieve primary sensitization in vitro is the most rational approach to a study of Ir genes in man.

Antibody Formation↗

Clinical trial of Ro 6-0787, a monovalent specific hapten inhibitor of penicillin allergy.

A second clinical trial of the compound Ro 6-0787, which is a specific monovalent penicilloyl hapten inhibitor of allergic reactions to penicillin has been conducted by investigators from 9 different European groups in 90 patients allergic to penicillin. The effect of a combined Ro 6-0787-penicillin therapy was considered as clinically successful in the large majority of cases, since treatment with penicillin could be pursued or resumed without allergic manifestation in 42 from 46 cases (91 percent). The effect of Ro 6-0787 alone on acute allergic manifestations after interruption of penicillin therapy was more difficult to evaluate but was nevertheless considered satisfactory in 17 from 26 patients (65 percent). A depression of skin hypersensitivity to PPL and/or penicillin and penicillin derivatives sometimes persisting for weeks and months was obvious in numerous allergic patients submitted to combined Ro 6-0787-penicillin treatment. A depressing effect on antipenicillin antibody titers detected by passive hemaglutination was also manifest in some patients. Failure to suppress allergic manifestations was reported in 11 cases, among which some may have been due to insufficient dosage of inhibiting hapten. The overall tolerance of Ro 6-0787 in allergic patients has been very good. Nevertheless, the major obstacle to a wider general use of Ro 6-0787 at the present time appears to be the occurrence of positive skin reactions to that compound in approximately 5 percent of patients allergic to penicillin. It is not yet ascertained whether the occasional positive skin reactions and urticaria to Ro 6-0787 may have been due to aggregation, or incomplete dissolution of the compound or whether it reflects hypersensitivity to another antigenic determinant. With the reservation that patients with positive skin test to Ro 6-0787 have for the time being to be excluded from combined treatment, this monovalent hapten certainly offers a new possibility to resume and/or pursue penicillin therapy in patients demonstrably allergic to that drug.

Adolescent↗