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K P Mathews

Publications and source records attributed to K P Mathews.

At least 19 recordsLinked to original sources
PubMed1995

Improved method for measuring C1-r-C1-s-(C1 inh)2 complexes by an enzyme-linked immunosorbent assay.

Measurement of C1-r-C1-s-(C1 inh)2 complexes in serum or plasma by enzyme-linked immunosorbent assay (ELISA) has been proposed as a relatively convenient and sensitive means for assessing C1 activation. However, interference by unactivated C1q (r-s)2 at low serum or plasma dilutions has resulted in estimates that vary widely with the degree of serum or plasma dilution. Precipitating the interfering C1q (r-s)2 with 6% polyethylene glycol has been proposed to resolve this problem, but here it is shown that this procedure also precipitates or coprecipitates some of the C1-r-C1-s-(C1 inh)2 complexes. Satisfactory results have been achieved without PEG precipitation by testing high plasma dilutions under conditions where there is a sufficient excess of anti-C1s coating the microtitration plate wells that removal of C1q (r-s)2 is not necessary. Optimizing conditions for quantitating these complexes at high dilution have been investigated. The mean normal EDTA plasma C1-r-C1-s-(C1 inh)2 complex measurement was 36.6 +/- 7.0 (S.D.) ELISA units with a 95% confidence interval of 19.5-47.6u. Besides providing a sensitive assay for C1 activation, measuring C1-r-C1-s-(C1 inh)2 complexes may help to clarify the pathophysiologic mechanisms resulting from C1 inh deficiency under various conditions.

Adult↗
PubMed1992

Cold-dependent activation of complement: recognition, assessment, and mechanism.

Cold-dependent activation of complement (CDAC) is a phenomenon characterized by low hemolytic complement activity in chilled serum. Complement component levels are normal when measured immunologically, and there is normal hemolytic activity in EDTA plasma or serum maintained at 37 degrees C. Little attention has been paid to CDAC except in Japan, and current unfamiliarity with it, even by clinical immunologists, can lead to confusion and unnecessary laboratory tests. A 66-year-old patient with a complex medical history is described whose complement tests showed abnormalities characteristic of CDAC. Evidence for classical complement pathway activation in the cold was obtained by CH50 measurements, by hemolytic C4 determinations, by C4a, C3a, and C4d generation, and by quantitating C1s-C1r-(C1 inhibitor)2 complexes. A good correlation was observed among these parameters. Cryoprecipitates were absent. CDAC activity has persisted for over 5 years and is greater at 13 than at 4 degrees C. Activation is ablated by heating at 56 degrees C and restored by the addition of C1 to the heated serum. Adsorption by streptococcal protein G-Sepharose and precipitation by 2.5% polyethylene glycol support the hypothesis that CDAC is caused by aggregated IgG. The CDAC factor(s) also induces complement activation in normal serum but has not interfered with Raji cell or C1q binding tests or with FACS analysis. More limited studies of a second individual experiencing CDAC yielded similar results.

Adult↗
PubMed1987

Rhinitis and asthma.

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Adrenergic beta-Agonists↗
PubMed1987

Controlled clinical assessment of astemizole in the treatment of chronic idiopathic urticaria and angioedema.

Astemizole, one of the newer generation of nonsedating antihistamines, was evaluated in a double-blind study of forty-six patients who had chronic idiopathic urticaria with or without angioedema; most had severe disease. Nineteen of twenty-three patients who were on placebo discontinued treatment because of lack of response compared to only five of twenty-three astemizole-treated patients (p less than 0.0001). Fourteen of twenty-two astemizole-treated patients and two of twenty-two placebo-treated patients considered the results to be good or excellent (p less than 0.0001). Blinded assessment by the investigators yielded similar results (p less than 0.0001). Therapeutic response was the same in patients with and without angioedema in addition to urticaria and in those requiring corticosteroids. Duration of urticaria also did not influence the results. Increased appetite and weight gain were the main side effects reported more frequently in the astemizole-treated than in the placebo-treated group, and no significant toxicity was noted. Follow-up after terminating the drug study indicated a high frequency of remissions during the subsequent year.

Adult↗
PubMed1986

Decreased synthesis of serum carboxypeptidase N (SCPN) in familial SCPN deficiency.

Serum carboxypeptidase N (SCPN) is the primary inactivator of the C3a, C4a, and C5a anaphylatoxins as well as an inactivator of bradykinin. Thus SCPN deficiency potentially could result in significant pathophysiologic consequences. Previous studies identified a deficient subject afflicted with frequent episodes of angioedema, and other family members also had SCPN deficiency. To delineate this abnormality further, the fractional catabolic rate (FRC) and enzyme synthesis were determined in three members of the afflicted kindred as well as in five normal persons following the infusion of homogeneous 125I-SCPN. The mean FCR and synthesis rates for SCPN in the normal subjects were 1.3%/hr and 20,793 U/kg/hr, respectively. Reduced synthesis was concluded to be primarily responsible for the low SCPN levels in the afflicted kindred. The high FRC of SCPN discourages attempted maintenance therapy with infusions of enriched SCPN preparations.

Carboxypeptidases↗
PubMed1986

Generation of drug metabolite antigenicity in the intestinal mucosa.

Both nitroreductase and transglutaminase activities have been assayed in the 10,000 X g supernatant fluids of rat intestine homogenates after Triton X-100 treatment. Incubation of 14C-nitrofurantoin in the intestine extract yielded protein-bound 14C-labeled products. Injection into rabbits of the conjugated protein similarly prepared with unlabeled nitrofurantoin elicited formation of antibodies against nitrofurantoin. These results suggest that intestinal metabolism and conjugation to protein of orally administered drugs may serve as a probable mechanism of drug allergy, and this may be accomplished by enzymatic coupling of relatively stable drug metabolites to protein carriers.

Animals↗
PubMed1986

Plasma protease inhibitor and anaphylatoxin inactivator levels in chronic urticaria/angioedema and in patients experiencing anaphylactoid reactions to radiographic contrast media.

Since a protease inhibitor or anaphylatoxin inactivator deficiency might explain why certain individuals are prone to develop chronic urticaria/angioedema or anaphylactoid reactions to radiographic contrast media, serum alpha 1-protease inhibitor, alpha 1-antichymotrypsin, alpha 2-macroglobulin, inter-alpha-inhibitor, antithrombin III, alpha 2-plasmin inhibitor, C1 inhibitor, and serum carboxypeptidase N were assessed by immunologic or functional methods. These values all were within normal limits in both groups of patients except for a low mean alpha 1-protease inhibitor level in chronic idiopathic urticaria/angioedema and cold urticaria patients and marginal decreases of alpha 1-protease and inter-alpha-inhibitor levels in radiographic contrast medium reactors. However, these abnormalities were not thought to be of pathogenetic significance.

Anaphylatoxins↗
PubMed1985

Occupational asthma caused by sewer flies.

Insect emanations occasionally cause allergic asthma, which not infrequently is due to occupational exposures. This second report of asthma caused by sewer flies, Psychoda alternata, concerns a sewage plant worker who previously had developed immediate-type hypersensitivity to wax moths. Evidence for sewer fly allergy was derived from direct prick and intracutaneous skin tests, Prausnitz-Kustner testing, in vitro leukocyte histamine release, ELISA, and bronchial provocative challenge. The ELISA inhibition tests indicated little cross-reactivity between sewer fly and wax moth extract or midge hemoglobin, but direct skin testing suggested possible hypersensitivity to other families of the order Diptera.

Asthma↗
PubMed1985

Aspirin-sensitive asthma.

Aspirin intolerance is particularly common in asthmatic patients who additionally have chronic rhinitis and/or nasal polyps. These individuals differ in several respects from patients who experience urticaria and/or angioedema after aspirin administration, and differing mechanisms may be involved. Data regarding the latter are indirect and incomplete, but suggest that ASA-sensitive asthma is most likely to be related in some manner to the capacity of ASA to inhibit cyclooxygenases, enhanced lipoxygenase metabolism perhaps playing a crucial role. Current research employing ASA "desensitization" may help to elucidate these enigmas.

Arachidonic Acid↗
PubMed1985

The urticarias. Current concepts in pathogenesis and treatment.

Urticaria is a very common disease which is often associated with angioedema. Release of histamine and perhaps other mediators from the cutaneous mast cells is believed to be the likeliest cause for the development of these wheals in most instances, but there may be both non-immunological as well as immunological inputs into this final common pathway. The former include trauma, cholinergic mechanisms and non-immunological histamine release by drugs. Immune mechanisms most commonly are of the IgE-mediated type, but occasionally the activation of complement or other mediators of hypersensitivity may be involved. Drug and food allergy are among the most common causes of acute urticaria, but there are numerous other possibilities which mandate a thorough general medical history and physical examination (including ruling out infection, connective tissue disease and neoplasms). In cases of chronic urticaria, when the lesions have persisted for longer than about 2 months, no cause for the disease is discernable in most instances. However, in these cases, as well as in acute urticaria, symptomatic treatment generally can provide substantial symptom relief, with emphasis on the astute use of various types of antihistamines.

Adrenal Cortex Hormones↗
PubMed1984

Clinical spectrum of allergic and pseudoallergic drug reactions.

Among the many types of adverse effects of drugs, allergic reactions constitute a very significant minority, with respect to both their frequency and sometimes serious consequences. To keep the term "drug allergy" meaningful, it should be limited to those adverse drug reactions that are based on immune mechanisms or that can reasonably be presumed to have this basis. Pseudoallergic drug reactions, which will also be considered in this issue, have similar clinical manifestations and some common pathogenetic mechanisms, but the initiating event does not appear to involve a reaction between the drug or a drug metabolite and specific antibodies. Clinically, drug allergy is commonly observed in nonatopic as well as atopic people. Innumerable drugs have been reported to produce these types of reactions, but in many instances drug metabolites may be the actual culprits. Clinical manifestations of drug allergy also are legion. Unfortunately, essentially none of these is unique or specific for drug allergy, but it is important for clinicians to think of this very treatable condition along with other diagnostic possibilities. It is convenient and helpful to classify allergic reactions to drugs according to Gell and Coombs' four main types of hypersensitivity processes, but in many instances more than one mechanism may be involved, just as immune responses to most antigens generally are complex. Type I reactions are generally immunoglobulin (Ig) E-mediated, and clinical manifestations include urticaria, angioedema, respiratory symptoms, and anaphylaxis. Pseudoallergic reactions of the latter type are called anaphylactoid.(ABSTRACT TRUNCATED AT 250 WORDS)

Anaphylatoxins↗
PubMed1984

Distribution and clearance of radioactive aerosol on the nasal mucosa.

The distribution and clearance of aerosolized radioactive technetium 99m pertechnate in physiologic buffered saline was analyzed in four human adult asymptomatic volunteers following delivery into one nostril in the same manner as for nasal challenge testing (i.e., 0.1 ml via a 251 DeVilbiss atomizer powered by a compressor delivering 0.10 +/- 0.01 gm/spray). For comparison, squeeze bottles and spray bottles from commercial sources, a 114 and a 127 DeVilbiss atomizer, and a pipette were employed. Lateral imagery via minicomputer processing was used to determine both distribution and clearance of the radiotracer. The counts after 1 minute were lower following pipette delivery than with the other devices. None yielded discernable , wide-spread distribution of aerosol throughout the nasal cavity. Following delivery from the 251 atomizer, mean clearance at 17 minutes was 60.0%. Similar clearance rates were obtained with the other spraying methods except for lower values with the squeeze bottle. Analysis of six hour clearance studies by linear regression showed a relatively rapid initial phase, which is probably due largely to mucociliary clearance, and a prolonged late phase related to the very slow disappearance of residual material located far anteriorly in the nose. Achieving good initial retention and rapid clearance of material deposited anteriorly in the nose are desirable attributes of devices employed for administering materials intranasally.

Administration, Intranasal↗
PubMed1983

Indomethacin inhibition of glutathione S-transferases.

Indomethacin inhibited rat liver glutathione S-transferases (EC 2.5.1.18). Its inhibition was non-competitive with respect to 3,4-dichloronitrobenzene with an apparent Ki of 5.3 X 10(-5) M and uncompetitive with respect to glutathione with an apparent Ki of 4.0 X 10(-5) M. 4-Chlorobenzoic acid and 5-methoxy-2-methylindole-3-acetic acid, two metabolites of indomethacin, were weak inhibitors of the enzymes. On the other hand, meclofenamic acid was a competitive inhibitor of the enzymes with an apparent Ki of 3.0 X 10(-4) M. Possible significance of these findings in arachidonic acid metabolism is discussed.

Animals↗
PubMed1983

Effects of aspirin on nasal responses in atopic subjects.

Preliminary experiments indicated that solutions of aspirin (ASA) in buffered saline, pH 7.35, did not significantly change nasal airways resistance (NAR) when 0.1 ml of solution containing 22.5 mg (or less) per deciliter was sprayed into each nostril. Subsequently it was shown that this quantity of ASA administered intranasally did not significantly change NAR responses 15 min later to intranasal administration of increasing concentrations of histamine, methacholine, or an irritant (NH3 gas). However, the same atopic subjects demonstrated significantly decreased responses to intranasal challenge with short ragweed extract (SRW) after intranasal ASA. In addition, prior oral administration of ASA, Na salicylate, and indomethacin significantly inhibited nasal challenge responses to SRW in sensitive subjects under controlled conditions.

Administration, Intranasal↗