Kurt J. Bloch

Immunoglobulins on the surface of neoplastic lymphocytes.

Abstract Peripheral lymphocytes from 25 patients with chronic lymphocytic leukemia (CLL) and three with chronic lymphosarcoma-cell leukemia, and lymph-node cells from three of four with lymphocytic lymphoma bore on their cell surface IgM, which was readily demonstrated with fluorescein-conjugated antiserums. The lymphosarcoma cell differed from the cell of CLL in possessing much more surface immunoglobulin. Light-chain analysis of the surface IgM showed that cells bore either kappa or lambda determinants, but not both, indicating the clonal nature of these neoplasms. The serum of four leukemic patients was also found to contain small amounts of IgM M-components. Since the B lymphocyte (bone-marrow-derived) of laboratory animals bears large amounts of surface immunoglobulin and the T lymphocyte (thymus processed) does not, the findings favor the B-cell origin of these leukemic cells. A less likely possibility is that the CLL lymphocyte is a derepressed T cell.

Cell-surface immunoglobulins in chronic lymphocytic leukemia and allied disorders.

Abstract Immunoglobulin on the surface of peripheral blood lymphocytes from 57 patients with chronic lymphocytic leukemia (CLL) and allied disorders was investigated by fluorescence microscopy and correlated with circulating immunoglobulin. In 38 of 48 patients with CLL, the predominant surface immunoglobulin identified on peripheral blood lymphocytes was M (IgM) of either kappa or lambda light chain type. In five patients, the predominant surface protein was immunoglobulin G (IgG) of either kappa or lambda type. In three others, the lymphocyte surface immunoglobulin could not be definitely identified and in two, no surface immunoglobulin was detected. Circulating immunoglobulin levels, particularly IgM, were depressed in the majority of patients with CLL. In three subjects with IgM-bearing lymphocytes, the serum contained a circulating IgM M component and three of the five subjects with IgG-bearing cells, had a circulating IgG M component. In three patients with CLL, immunoglobulin disappeared from the cell surface with progression of the disorder, although neoplastic cells remained in the circulation. The amount of immunoglobulin on the surface of cells from patients with chronic lymphosarcoma cell leukemia was much greater than that on cells from patients with CLL, and the surface immunoglobulin pattern in hairy cell leukemia also appeared distinctive. Study of immunoglobulin on the surface of lymphocytes has helped to define the cellular origin and monoclonal nature of CLL, the source of circulating M components in this disease, and the relationship of CLL to other lymphoproliferative disorders. Although technically demanding, the study of surface immunoglobulin should prove useful in clinical medicine.

Intestinal Uptake of Macromolecules: Effect of Oral Immunization

Animals were orally immunized with horseradish peroxidase and bovine serum albumin, and absorption of these antigens was studied. In comparison with controls, a consistent and significant decrease in peroxidase uptake was noted in both germ-free and conventional rats immunized with peroxidase; a similar decrease in serum albumin uptake was also noted in animals immunized with serum albumin. There was no difference in the uptake of an unrelated macromolecule. These observations suggest that local immunization interferes specifically with the intestinal uptake of macromolecular antigens.

Increased Susceptibility to Infection in a Patient with Type II Essential Hypercatabolism of C3

Abstract In a patient with partial lipodystrophy and increased susceptibility to infection, no abnormalities were found in humoral antibody, cellular immunity or leukocyte function. In contrast, the patients serum complement-mediated functions were grossly deficient. The concentrations of the components of the serum complement and properdin systems were normal, except for that of C3, which was markedly reduced and consisted of native C3 and an inactive conversion product, C3c. The patients serum contained an enzyme, C3ase, capable of cleaving C3 in vitro and in vivo. Addition of purified C3 to the patients serum improved complement-mediated phagocytosis and killing of bacteria. In this Type II disorder, low serum C3 levels are ascribable to both hyposynthesis and hypercatabolism of this component of complement.

Anaphylaxis during induction of general anesthesia: Subsequent evaluation and management

Twenty-seven patients were referred for evaluation of anaphylaxis after induction of general anesthesia (GA) in which thiobarbiturates, muscle relaxants, or antibiotics were administered intravenously. Skin testing by the prick and intracutaneous methods was performed with dilutions of the thiobarbiturates and muscle relaxants; beta-lactam reagents were used in patients who had also received these drugs. No skin test reactivity was noted in 16 normal subjects. Skin tests were positive in 13 patients (thiobarbiturates in five, muscle relaxants in six, and antibiotics in two patients). Two patients were dermatographic and yielded indeterminate skin test results. Eleven of the 27 patients subsequently had GA; all patients received a premedication regimen of prednisone and diphenhydramine. Of three patients with negative skin tests, one experienced an arrhythmia, but no other signs attributable to anaphylaxis were noted. One patient with dermatographism had GA without a reaction. Positive skin tests implicated an agent that was avoided in seven patients; one of these patients experienced delayed urticaria/angioedema after the completion of GA. Thus, no patients developed anaphylaxis during subsequent GA for which agents producing positive skin tests were avoided, and a premedication regimen was used.

Ocular anaphylaxis induced in the rat by topical application of compound 48/80. Dose response and time course study.

Abstract In the present study we sought to develop a model of ocular anaphylaxis based on the topical application of compound 48/80 to the surface of the rat eye. Doses ranging from 50 to 1000 μg were found to produce graded edema of the conjunctiva and swelling of the lid. On histologic examination, 50 μm compound 48/80 produced no changes distinguishable from those in PBS‐treated controls, 150 μm produced mild alterations, and 250, 500, and 1000 μg compound 48/80 produced a marked increase in degranulated mast cells and a mild influx of neutrophils. The time course of the response to 250 μg and 1000 μg of compound 48/80 was evaluated over a 72‐h period. Both doses elicited epithelial damage. A mild reduction in the number of mast cell was seen at 6 h in rats receiving 250 or 1000 μg. The reduction persisted to 72 h in rats receiving 1000 μg. The number of neutrophils was increased at 1 and 6 h in eyes treated with 250 (ig and at 1,6, and 24 h in eyes treated with 1000 [ig compound 48/80. The clinical and histologic changes induced by application of 250 jig compound 48/80 resemble those seen in patients with allergic conjunctivitis suggesting that a model of ocular anaphylaxis based on the topical application compound 48/80 will be clinically relevant and experimentally practical.

Intestinal Uptake of Macromolecules. VI. Uptake of Protein Antigen In Vivo in Normal Rats and in Rats Infected with Nippostrongylus brasiliensis or Subjected to Mild Systemic Anaphylaxis

Adult Sprague-Dawley rats weighing approximately g were fed bovine serum albumin and sodium bicarbonate by gavage. Serum was obtained at intervals after feeding and tested for immunoreactive bovine serum albumin by radioimmunoassay. Nanogram amounts of immunoreactive bovine serum albumin were detected in serum; peak values were obtained after 4 and 6 hr. The influence of intestinal inflammation on protein uptake was examined in two model systems. Infection of rats with Nippostrongylus brasiliensis was accompanied by partial villous atrophy in the intestinal segments harboring adult worms and mild systemic anaphylaxis in the rat was accompanied by increased intestinal vascular and mucosal permeability. Enhanced uptake of BSA was observed before and shortly after self-cure of infection and during mild systemic anaphylaxis. The molecular size of immunoreactive bovine serum albumin approximated that of the administered bovine serum albumin; no small fragments of bovine serum albumin bearing antigenic determinants were detected.

In vivo effect of UV-B on lymphocyte function

Whole‐body exposure of normal subjects to erythemogenic doses of UV‐B radiation results in a decrease in the proportion of circulating E‐rosette‐forming lymphocytes, an increase in the proportion of null cells and a decreased incorporation of tridated thymidine into DNA of lymphocytes following stimulation by phytohaemagglutinin (PHA). These alterations are dose‐dependent, appear soon after exposure, reach a maximum after 8–12 h, and are reversed by 48–72 h post exposure.

Acute eosinophilic hepatitis from trovafloxacin.

To the Editor: According to the Food and Drug Administration, trovafloxacin, a broad-spectrum quinolone antibiotic, has been associated with more than 100 cases of hepatic toxicity. Fourteen of the...

Effect of locally induced intestinal anaphylaxis on the uptake of a bystander antigen

Adult Sprague-Dawley rats weighing 250 gm were immunized with 100 micrograms egg albumin (EA) and alum. Fourteen days later, intestinal anaphylaxis was induced by intraduodenal or intragastric challenge with EA. To test for the changes in vascular and mucosal permeability that accompany anaphylaxis, the rats were injected intravenously with 125I-rat serum albumin (RSA) at the time of challenge and the amount of radioactivity retained in the wall of gut segments, as well as the trichloroacetic acid (TCA)-precipitable radioactivity present in the secretions obtained from these segments, was determined. Enhanced retention of 125I-RSA was found in the wall of the duodenum and first and second halves of the small intestine, and increased amounts of TCA-precipitable radioactivity was found in gut segments obtained from antigen-challenged compared with buffer-challenged rats. In other EA-immunized rats bovine serum albumin (BSA) was administered by gavage 1 hr before challenge with EA. Increased amounts of immunoreactive BSA were detected by radioimmunoassay in the serum of rats subjected to local intestinal anaphylaxis. Possible consequences of the enhanced systemic uptake of protein present during local intestinal anaphylaxis were considered. It was suggested that such proteins might induce an IgE antibody response, thereby broadening the anaphylactic sensitivity of the animal to additional antigens.