Familial properdin deficiency and fatal meningococcemia. Correction of the bactericidal defect by vaccination.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
J M Weiler
Publications and source records attributed to J M Weiler.
Airway responses to methacholine in asymptomatic nonatopic cigarette smokers.
We prospectively performed methacholine bronchoprovocation challenges on 46 young smokers to examine the effects of cigarette smoking on airway responsiveness. The subjects, ages 18-35 yr, had no past or present history or physical examination findings of asthma or other lung diseases, rhinitis, allergic diseases, or respiratory infections; were skin test negative to 29 common aeroallergens; and had base-line pulmonary function values greater than 80% predicted. Sixteen of 46 (35%) subjects had a 20% or greater drop in forced expiratory volume in 1 s at a provocative methacholine concentration less than or equal to 25 mg/ml. The degree of methacholine responsiveness was not dependent upon base-line pulmonary function values or the amount of cigarettes consumed, and there was no association between the amount of cigarettes consumed and base-line pulmonary function values. These data suggest that many young asymptomatic nonatopic smokers have increased airway responsiveness to inhaled methacholine without clinically significant hyperreactive airway disease.
Adolescent↗
Safety and efficacy of loratadine (Sch-29851): a new non-sedating antihistamine in seasonal allergic rhinitis.
Loratadine, a new antihistamine in the non-sedating class, was evaluated for efficacy and safety in treatment of allergic rhinitis in a multicentered study. Loratadine was found to be both safe and efficacious. When administered to patients with seasonal allergic rhinitis, a single daily oral dose of 10 mg is comparable in efficacy to clemastine, 1 mg, given twice daily. The incidence of sedation with loratadine is comparable to placebo and significantly lower than with clemastine. The incidence of anticholinergic side effects with loratadine is low and in this study was comparable to placebo and clemastine.
Capsules↗
Role of the third component of complement in immunoregulation.
Explore the source record for details and available documents.
Animals↗
Prevalence of bronchial hyperresponsiveness in highly trained athletes.
Previous studies indicated that the prevalence of symptomatic asthma is about 4 to 7 percent. No similar studies exist to suggest the prevalence of asthma in highly trained competitive athletes, since asthma is thought to be an uncommon disease in this population. We became concerned, therefore, when a large number of football players developed symptoms consistent with asthma during preparation in California for the Rose Bowl in December 1981. We studied the team and found 12 percent of the football players admitted to a history of asthma, whereas none of the members of the university basketball team and 7 percent of a group of sophomore medical students and physician assistant students gave a history of asthma. Furthermore, 19 percent of the football players indicated that at some time they had chest tightness, cough, wheezing, or prolonged shortness of breath after exercise; 12 percent of the basketball players and 37 percent of the students indicated such a history. We examined each of these three groups for non-specific bronchial hyperresponsiveness to inhaled methacholine using a modified methacholine bronchoprovocation (MBP) challenge and found that 76 of 151 (50 percent) football players tested had positive tests; 76 percent of those with symptoms had positive results of inhalation tests and 47 percent of those with minimal or no symptoms had positive test results. In addition, four of 16 (25 percent) basketball players and 69 of 167 (41 percent) students had positive MBP tests. These studies indicate that bronchial hyperresponsiveness to inhaled methacholine is much more common in these young adults than has previously been suspected.
Adolescent↗
Human secondary immune responses induced by influenza in a serum-free tissue culture system.
Peripheral blood lymphocytes are capable of producing antibody in response to antigenic stimulation by a recall antigen, influenza, during culture for 10 days in medium consisting of 1 part Ham's F-12 and 1 part Iscove's modified Dulbecco's medium supplemented with sodium bicarbonate, bovine crystalline insulin, human transferrin, 2-mercaptoethanol, progesterone, and bovine serum albumin. Anti-influenza antibody levels in the supernatants were determined by enzyme-linked immunosorbent assay. Optimal conditions for production of anti-influenza antibody in this serum-free medium were: influenza concentration, 0.032-0.125 HAU/ml; day of harvest, 10; and cell concentration, 3.0-4.0 X 10(5) cells in 200 microliter of medium per well. Use of serum-free medium will allow examination of the effects of various additives to tissue culture without concern for unknown factors or potential interaction with serum.
Antibodies, Viral↗
Serious adverse reactions to protamine sulfate: are alternatives needed?
Protamine sulfate is a strongly cationic polypeptide that is used commonly in clinical medicine. It is administered regularly after cardiac catheterization, cardiothoracic and vascular surgical procedures, and less frequently after dialysis and leukapheresis because of its capacity to reverse the anticoagulant activity of heparin. In addition, because it delays the absorption of insulin, protamine is combined with insulin in protamine zinc insulin and neutral protamine Hagedorn insulin. Recently, there have been reports of adverse reactions to protamine (Table I). Although most of these reactions were relatively mild, three were fatal; one was clearly the result of type I anaphylaxis. Reactions occur predominantly in patients who were previously exposed to protamine through protamine-containing insulins or during heparin neutralization. Almost 50% of these patients were diabetic; most of whom received neutral protamine Hagedorn insulin, thereby enhancing their chance for presensitization. In 1983 we encountered three patients who suffered adverse reactions to protamine sulfate. Two of these patients will be presented here; the third patient, who died of IgE-mediated anaphylaxis, has already been reported and therefore is mentioned only briefly. We shall discuss adverse reactions to protamine sulfate and alternatives to the routine use of this drug.
Aged↗
Contamination of intradermal skin test syringes.
Syringes used in intradermal skin testing have commonly been used for multiple patients. Recently the safety of this practice was questioned, raising the possibility that these syringes may transmit disease from one patient to another. Since this practice is so widespread and because of a scarcity of articles linking the spread of disease with this practice, we repeated these studies and performed other experiments to test this hypothesis. With the use of Escherichia coli, Staphylococcus aureus, and tritiated thymidine, we found contamination of syringe contents that indicated a clear potential for common syringes to spread disease. These studies and studies reported elsewhere suggest that common syringes should not be used in skin testing.
Equipment Contamination↗
Small heparin fragments regulate the amplification pathway of complement.
Heparin is a highly sulfated, polydisperse and heterogeneous glycosaminoglycan which has been well characterized for its ability to regulate multiple sites in the complement cascade. Although previous studies demonstrated the relationship between degree of sulfation, particularly O-sulfation, and complement inhibiting capacity, they left unclear the relationship between the size of the heparin molecule and its ability to inhibit complement. Therefore, although the structure-activity relationship for heparin is well understood for anticoagulant activity, it is ill defined for the complement system. The present studies were designed to examine depolymerized heparin to determine which fragments were capable of inhibiting amplification pathway activation. We found that as the size of the molecule increases the ability to regulate complement increases; below 1000 Da the fragments were essentially inactive and above 3500 Da they had the same activity as does commercial heparin. Furthermore, we examined the five major tetrasaccharides of heparin and found that the degree of sulfation did correlate with the ability to inhibit complement. These studies have for the first time begun to examine the minimal structural requirements for heparin to regulate complement.
Complement Activation↗
Protamine-induced fatal anaphylaxis. Prevalence of antiprotamine immunoglobulin E antibody.
Protamine is used widely to reverse the anticoagulant effects of heparin and to delay the absorption of insulin. Although adverse reactions to protamine are reported infrequently and are usually mild, we recently observed the first fatal case of type I anaphylaxis resulting from protamine. This patient had previously been sensitized to protamine during cardiac catheterization and had high levels of protamine-specific immunoglobulin E in the serum. In a prospective study, we found that 10 of 19 diabetic patients (53%) who had received insulin containing insulin also had high levels of antiprotamine immunoglobulin E. In contrast, none of 27 nondiabetic healthy normal controls or 10 diabetics who had never received protamine or protamine-containing insulin had levels of antiprotamine immunoglobulin E over background. This study underscores the risks of routinely administering protamine to susceptible individuals and the need for alternative therapies.
Adolescent↗
Role of complement in the immune response.
Evidence has accumulated that shows that fragments of C3 are potent inhibitors of immune responses. A low-molecular-weight fragment of C3 and fragments possessing leukocyte-mobilizing activity have been shown to block both antigen- and mitogen-induced human T cell proliferation, and to block mixed lymphocyte culture responses and the generation of cytotoxic lymphocytes. The same fragments inhibit the development of secondary in vitro antibody responses of rat lymphocytes. C3b can be shown to inhibit the polyclonal activation of human lymphocytes by pokeweed mitogen, but it has no effect on T cell proliferation or on the generation of cytotoxic T cells. We now propose that different C3 fragments selectively act on various lymphocyte subsets and thus play a profound role in regulating both immune effector functions and the intensity of the immune response.
Animals↗
C1 INH deficiency and angioedema: a spectrum of disease. Part one.
Explore the source record for details and available documents.
Adult↗
C1 INH deficiency and angioedema: a spectrum of disease. Part two.
Explore the source record for details and available documents.
Adult↗
Human immunoglobulin biosynthesis in a serum-free medium.
We have previously reported that human peripheral blood lymphocytes are able to survive and undergo blastogenesis when cultured under serum-free conditions. Now we report that peripheral blood lymphocytes are capable of producing immunoglobulins in response to polyclonal activation during culture for 10 days in medium consisting of one part Ham's F-12 and one part Iscove's modified Dulbecco's medium supplemented with sodium bicarbonate, bovine crystalline insulin, human transferrin, 2-mercaptoethanol, and bovine serum albumin. Immunoglobulin levels in tissue culture supernatants obtained on day 10 were determined by enzyme-linked immunosorbent assay and were analyzed using a new computer program. Pokeweed mitogen was used as the polyclonal activator, and it stimulated immunoglobulin biosynthesis as well in serum-free medium as in medium that contained fetal calf serum. Immunoglobulin production in serum-free medium began on day 4 and continued through day 9, with peak production on days 5 to 8. Optimal conditions in serum-free medium were: PWM dose, 1:400 to 1:800; day of harvest, 10; and cell concentration, 3.5 X 10(5) cells in 200 microliters of medium per well. Use of this serum-free medium will allow examination of the effects of various additives to tissue culture without concern for unknown factors, components, influences, or potential interaction with serum.
Blood Donors↗
Termination of tritiated thymidine incorporation by freezing the cells.
It is often desirable to be able to stop the uptake of tritiated thymidine by a number of transforming lymphocyte cultures at a specific time. This is important for kinetic studies but may be difficult if the number of cultures to be harvested at one time is large. We describe in this report a simple method to stop the incorporation of tritiated thymidine into any number of transforming lymphocyte cultures simultaneously.
Freezing↗
Complement inhibits immune responses: C3 preparations inhibit the generation of human cytotoxic T lymphocytes.
C3 fragments have been shown to inhibit mitogen- and antigen-induced human lymphocyte blastogenesis. In this study, C3 preparations and a small fragment of C3 (contained in a preparation called Fraction 2) were examined for their capacity to regulate cytotoxic T lymphocytes (CTL) and proliferative mixed lymphocyte responses (MLR). We found that both preparations inhibited the generation of allogeneic human CTL as well as MLR in a dose-related manner. In contrast, Fraction 1, which contained native C3 and C3b, did not inhibit the generation of CTL nor did it inhibit the MLR. The kinetics of inhibition of proliferation were divergent from the kinetics of inhibition of CTL generation; the active preparations inhibited proliferation significantly when added as late as day 5 of a 6-day culture, whereas no inhibition of CTL generation was seen when these preparations were added after day 3 of culture. Cultures in which C3 preparations caused complete inhibition of CTL generation had normal levels of the nonspecific, anomalous killer cell activity, as assayed on K 562 target cells. Furthermore, C3 preparations and Fraction 2 had no effect on the lytic function of differentiated CTL, on "spontaneous" natural killer cell activity or on interferon-induced augmentation of natural killer cell activity. These findings indicate that C3 fragments may play a negative role in the regulation of CTL responses.
Adult↗
Cimetidine-induced cutaneous vasculitis.
A rash developed in a man consistent with urticarial vasculitis as demonstrated by biopsy on each of two occasions that he was exposed to cimetidine. The vasculitis resolved on discontinuation of the drug. This is the first report demonstrating by biopsy and rechallenge that oral cimetidine therapy may cause type III hypersensitivity.
Cimetidine↗
Polyions regulate the alternative amplification pathway of complement.
Polyanion has previously been shown to inhibit generation of amplification pathway convertase of complement and to inhibit H-mediated decay of this complex. Polycations, protamine sulfate, and poly-l-lysine (PLL) were examined in this study for direct effects on alternative amplification pathway mechanisms and for ability to regulate polyanion-induced inhibiton; they were found to inhibit generation of EAC4b,3b,Bb, and EAC4b,3b,Bb,P in a dose-related manner. The generation of EAC4b,3b,B was also inhibited by higher doses but was augmented by lower doses of polycation. Polycation interfered with the effective consumption of B in the fluid phase, bound minimally to EAC4b,3b, and did not cause accelerated decay of a preformed convertase. Polycation diminished the ability of polyanion (heparin) to inhibit generation of both cell-bound and fluid-phase amplification pathway convertase. In contrast, polycation enhanced the ability of polyanion to cause decay of preformed convertase even though polycation had no effect itself. These studies demonstrate that both polyionic substances have the capacity to regulate amplification pathway mechanisms directly.
Cations↗