Henry G. Herrod

Side Effects Associated with Intravesical Mitomycin C

The nature and severity of side effects accompanying intravesical chemotherapy with mitomycin C were studied in 29 patients. No patient experienced systemic toxicity. Local side effects developed in 7 patients (24 per cent), and consisted of moderate cystitis in 3 and drug-related palmar desquamation, with or without generalized rash, in 4. Based on skin tests 3 of these patients were believed to have a contact dermatitis. The fourth patient had a generalized rash, in addition to palmar desquamation, that appeared after subsequent instillations of mitomycin C and the drug had to be discontinued. Careful cleansing of the hands and perineum on the day of treatment can prevent most skin reactions.

Selective antibody deficiency toHaemophilus influenzae type B capsular polysaccharide vaccination in children with recurrent respiratory tract infection

Fifty-one children between 22 and 158 months of age referred to an immunology clinic with a history of recurrent respiratory tract infections were prospectively evaluated for immunologic abnormalities. Ten of the subjects had a poor response to theHaemophilus influenzae type b (Hib) capsular polysaccharide vaccine (failure to mount a twofold increase in titer or achieve a postimmunization titer > 0.2 µg ab/ml). There were no differences in mean serum concentrations of IgG, IgM, IgA, isohemagglutinins, or anti-tetanus toxoid between the responders and the nonresponders. None of the 10 nonresponders were deficient in IgG2. Eight of the vaccine failures were immunized with an Hib conjugate vaccine (HbOC) consisting of Hib capsular oligosaccharides coupled to diphtheria toxin. All responded with at least a fivefold increase in antibody after primary immunization with HbOC. Seven of the eight had a postHbOC primary immunization titer greater than 1.0 µg/ml. This study demonstrates that some children with recurrent infections and with normal IgG subclasses are unable to respond to Hib capsular polysaccharide. This defect, which can be circumvented by presenting the polysaccharide antigen in an alternative form, may be contributing to the symptomatology experienced by these patients.

Characteristics of diatrizoate-induced basophil histamine release

Factors influencing the release of histamine by basophils exposed to the radiocontrast agent diatrizoate were investigated in vitro by use of cells from healthy adult subjects with no history of radiocontrast reactions. Diatrizoate-induced release shared similarities with calcium ionophore-induced release. The response to both agents is dose dependent, enhanced by deuterium oxide, optimal at 37 degrees C, calcium dependent, and enhanced with longer reaction times. Unlike calcium ionophore, however, pretreatment of basophils with diatrizoate may also induce dose-dependent inhibition of reactivity during subsequent challenges with anti-IgE, N-formyl methionine peptide, and calcium ionophore. These findings suggest that diatrizoate may induce histamine release via a calcium ionophore-like mechanism, but other effects on cellular function probably account for its ability to inhibit basophil responsiveness.

Serial immunologic studies in recipients of hepatic allografts

Thirty recipients of hepatic allografts had serial immunologic evaluations. Prior to transplant, patients had marked depression of lymphocyte subsets and impaired in vitro immunoglobulin synthesis, while phytohemagglutinin responsiveness was similar to that of controls. Following transplantation and introduction of cyclosporine and low-dose steroid therapy, there was a significant decline in both T cell subsets, but only the T4 population remained significantly depressed throughout the entire study period. The T4:T8 ratio in 5 patients who experienced acute rejection episodes was 1.4 +/- 0.6 prior to transplant. It increased to a mean of 2.0 +/- 0.6 by the time the diagnosis of rejection was made. By contrast, 12 subjects transplanted during a similar time period who did not demonstrate rejection had a T4:T8 ratio of 4.0 +/- 3.9 prior to transplant which fell to 1.5 +/- 0.6 (P less than 0.01) by 1 week post-transplant. In all 12 of these, the T4:T8 ratio fell in the 7 days post-transplant. The results indicate that monitoring the T4:T8 ratio in hepatic allograft recipients may be a useful marker for determining patients at risk for a rejection episode.

5′-Nucleotidase activity in subjects with abnormal lymphocyte function

Abstract5′-Nucleotidase (5′N) activity was determined in lymphocytes from patients with immunodeficiency diseases and in T-lymphocyte subpopulations from normal subjects. Cells from two patients with DiGeorge syndrome, with normal levels of B cells, and one patient with partial DiGeorge syndrome were found to have diminished 5′N activity. Utilizing monoclonal antibodies to deplete T-lymphocyte subpopulations, we found similar levels of 5′N in the cells remaining after depletion of OKT4- or OKT8-positive cells when 5′N values were determined after overnight incubation. If 5′N activity was determined on the day of the fractionation, however, OKT4-depleted cells had approximately threefold greater enzyme activity. These studies indicate that 5′N activity may vary in T lymphocyte subpopulations depending upon cell culture conditions. Diminished levels of 5′N activity are seen in patients with abnormal T-lymphocyte differentiation, as well as abnormalities of B-lymphocyte differentiation.

Impaired T-lymphocyte colony formation by cord blood mononuclear cells

When compared to adult mononuclear cells, cord blood mononuclear cells demonstrated significantly decreased T-lymphocyte colony formation (1351±643 vs 592±862,P<0.01). This diminished colony-forming activity did not appear to be associated with impaired responsiveness to the stimulant phytohemagglutinin or with excessive suppressor-cell activity. Irradiation reduced the colony-forming capacity of cord blood mononuclear cells more than it did that of adult mononuclear cells. Depletion of adherent cells reduced cord blood mononuclear-cell colony-forming capacity by 40%, while similar treatment reduced adult colony formation by 10%. Lymphocyte proliferation in liquid culture of cord and adult cells was minimally affected by these procedures. The colony-forming capacity of cord blood could be enhanced by the addition of irradiated adult cells (284±72 vs 752±78,P<0.01). This enhancement was demonstrated to be due to a soluble factor produced by a population of irradiated adult cells depleted of the OKT8+ subpopulation of lymphocytes. These results indicate that the progenitor cells of T-lymphocyte colonies in cord blood have distinct biologic characteristics when compared to colony progenitors present in adult blood. This assay may prove to be useful in our efforts to understand the differentiation of T-cell function in man.

Characterization of mononuclear cell-derived histamine release enhancing factor

Histamine release enhancing factor (HREF) is a product of phytohemagglutinin-stimulated mononuclear cells that substantially augments in vitro IgE-mediated basophil histamine release. The factor is stable at 56 degrees C and has a molecular weight in the 10,000 to 30,000 dalton range. The magnitude of HREF activity produced is dependent on the concentration of mononuclear cells cultured and the final concentration of HREF during basophil challenge. The HREF phenomenon could not be attributed to phytohemagglutinin, alpha- or gamma-interferon, arachidonic acid metabolites, or interleukin-1 or 2. HREF appears to be a unique cytokine of potential importance in the immunology of inflammatory and atopic processes.

In Vitro and in Vivo Activity of Two Second Generation Platinum Analogs in Murine Bladder Cancer

The activity of cis-diamminedichloroplatinum(II) was compared to two second generation platinum analogs, cis-diammine-1,1-cyclobutane dicarboxylate platinum(II) and cis-dichlorotransdihydroxybisisopropylamine platinum(IV) in the N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide-induced murine bladder tumor model and a tumor colony assay. Murine drug testing revealed that all three drugs were active against the MBT-2 tumor line, although cis-diamminedichloroplatinum(II) was more active than its analogs. All drugs produced enhanced inhibition of clonal growth with increasing drug exposure times. Cis-diamminedichloroplatinum(II) was more active against MBT-2 cells in the plateau growth phase versus the log growth phase after a one hour drug exposure. Similar differential activity depending upon the proliferative state of MBT-2 was not seen with the two platinum analogs. These two platinum analogs have somewhat less activity in vivo and in vitro than cis-diamminedichloroplatinum(II) and would be predicted to be less effective clinically in human bladder cancer than the parent compound.

T- and B-lymphocyte colony formation by cord and adult blood lymphocytes stimulated with Staph protein A

Abstract The response to staphylococcal protein A (SPA) of unfractionated, T-cell-enriched (TCE), and T-cell-depleted (TCD) populations of both adult mononuclear cells (AMC) and cord blood mononuclear cells (CBMC) was studied. Adult unfractionated and TCE populations formed more T-lymphocyte colonies than did similar populations of CBMC. However, TCD populations of CBMC formed B-lymphocyte colonies at least as well as did the TCD population of AMC. These results suggest that B cells from CBMC may be more mature than CBMC T-cell populations.