H James Wedner | University of Washington School of Medicine (original) (raw)

Papers by H James Wedner

Proceedings of the National Academy of Sciences of the United States of America, Nov 1, 1980

Clinical Immunology, May 1, 2023

Proceedings of the National Academy of Sciences of the United States of America, May 1, 1974

With immunofluorescent techniques it has been possible to show that bound cyclic AMP is uniformly... more With immunofluorescent techniques it has been possible to show that bound cyclic AMP is uniformly distributed in the nucleus and cytoplasm of a number of species-of cellular slime molds. One species (which does not respond to cyclic AMP as an acrasin) is an exception and has its cyclic AMP concentrated in the nucleus during the feeding and aggregation stage. In cell masses of Dictyostelium discoideum that show early signs of differentiation the anterior, prestalk cells contain more cyclic AMP than the posterior, prespore cells.

The Journal of Allergy and Clinical Immunology, Apr 1, 2023

Publisher Summary This chapter discusses the calcium ionophore and lymphocyte activation. Lymphoc... more Publisher Summary This chapter discusses the calcium ionophore and lymphocyte activation. Lymphocyte transformation induced by the mitogenic plant lectins, phytohemagglutinin, and concanavalin A, requires extracellular ionized calcium. These lectins induce prompt increases in Ca2+ uptake. These evidence suggest a central role for Ca2+ in lymphocyte activation. To evaluate the role of calcium in the activation of these cells, effects produced by the calcium ionophore were examined. In doing so, six biochemical parameters of activation were studied: (1) calcium uptake, (2) cyclic nucleotide accumulation, (3) membrane protein phosphorylation, (4) phosphatidylinositol turnover, (5) amino acid transport, and (6) DNA synthesis. Human lymphocytes were purified from peripheral venous blood by dextran sedimentation and isopyenic centrifugation. Ionophore concentrations under 1μg/ml were noncytotoxic. No consistent changes in cyclic GMP values were observed at noncytotoxic concentrations. Increases in lymphocyte membrane protein phosphorylation were seen with the ionophore.

The Journal of Allergy and Clinical Immunology, Feb 1, 2016

Birkhäuser Basel eBooks, 1987

Partheniurn (feverfew) is a small genus of Western Hemisphere plants of the Asteraceae included i... more Partheniurn (feverfew) is a small genus of Western Hemisphere plants of the Asteraceae included in the subtribe Ambrosiinae along with such well known genera as Ambrosia (ragweed) and Iva (marsh elder). One of the most common and biologically isolated species is P hysterophorus L. (Santa Maria feverfew), a ubiquitous annual weed native to the Gulf of Mexico region and West Indies but now widely distributed from Texas to southern Florida, and inland about 300 miles, especially in areas disturbed by humans (PICMAN and TOWERS 1982). P. hysterophorus (Ph) has been introduced elsewhere; for example, to the Poona region of India, and its subsequent spread in that subcontinent has given rise to a serious medical hazard as a major source of allergic contact dermatitis (ARLETTE and MITCHELL 1981).

Differentiation, Sep 1, 1979

Using indirect immunofluorescence technique, it has been possible to localize cyclic GMP in Polys... more Using indirect immunofluorescence technique, it has been possible to localize cyclic GMP in Polysphondylium violaceum cells. The bound cyclic nucleotide is localized throughout the cell during early stages, however, this staining increases and there is marked localization of cyclic GMP in the nuclear areas of the cells when aggregation is in full swing. Over 90% of the cells exhibited intense nuclear staining by 6 h and this decreased to less than 10% by 10 h.

Journal of Immunology, Jun 1, 1986

B cell triggering by bacterial lipopeptide involves both translocation and activation of the memb... more B cell triggering by bacterial lipopeptide involves both translocation and activation of the membrane-bound form of protein kinase C.

Journal of Experimental Medicine, Jul 1, 1976

Collagen is the major structural protein of connective tissues, comprising the bulk of the protei... more Collagen is the major structural protein of connective tissues, comprising the bulk of the protein in the extracellular matrix. Several studies have shown that collagen is also membrane bound in chick (1), rat (2), and mouse L-cell fibroblasts (3). Antibodies to membrane-bound collagen have been shown to evoke complement (C)-dependent cytotoxicity (1). These reports indicate that collagen synthesized by these fibroblasts may be deposited as fibrils in the extracellular matrix and also may be bound to the fibroblast membrane. Normal human skin fibroblasts have been shown to synthesize at least two genetically distinct types of collagen (4, 5). In this report, we present immunologic evidence that two antigenic types of collagens, type I collagen and a new collagen, type M (membrane) collagen, are associated with the normal human fibroblast membrane, and that antibodies to one of these collagens, type M collagen, can induce C-mediated cytotoxicity. Materials and Methods Preparation of Collagen Antigens. Type I collagen was prepared by acid extraction of human skin and purified according to the method of Bornstein and Piez (6). To obtain type III and type M collagen antigens, human placentas were pepsin digested and the supernate was sequentially salt precipitated at neutral pH with 0.15 M, 1.5 M, and 2.5 M NaC1. The type III collagen was further purified by carboxymethylcellulose (CMC) chromatography (7-9). Type I and type III collagens were judged to be pure by sodium dodecyl sulfate (SDS) 1 polyacrylamide gel electrophoresis (10) and amino acid analysis (7). Pepsin-treated type I collagen was prepared as previously described (5, 8, 9). Preparation of Antibodies to the Purified Collagens. Antibodies were raised by subcutaneous immunization of rabbits with 5-10 mg of heat-denatured collagen in 1.0 ml of 0.15 M NaCl, 0.05

Journal of Immunology, Oct 1, 1985

The role of glutathione (GSH) in lectin-induced lymphocyte activation can be studied by quantitat... more The role of glutathione (GSH) in lectin-induced lymphocyte activation can be studied by quantitating lectin-induced nuclear size transformation in the presence of variable degrees of GSH depletion. Buthionine sulfoximine (BSO) inhibits intracellular GSH synthesis by inhibition of the enzyme gamma-glutamyl-cysteine synthetase. By combining endogenous GSH depletion in cell cultures with BSO-induced inhibition of GSH synthesis, lectin-induced lymphocyte activation can be studied at various concentrations of soluble intracellular GSH. With this approach, the percentage of lymphocytes undergoing a nuclear size transformation is minimally affected despite depletion of soluble intracellular GSH to 0.27 nmol/10(7) cells (PBL), which represents approximately 95% depletion of intracellular GSH. When soluble intracellular GSH is depleted to undetectable levels (less than 0.10 nmol/10(7) cells) there is a 10 to 12% reduction in the number of cell nuclei transformed. However, in all BSO-pretreated cultures the lectin-induced nuclear size transformation is intermediate between resting and blast-transformed lymphocytes, suggesting only partial (or aborted) activation. The partial activation response observed in BSO-pretreated cultures may be due to mobilization of the protein-bound pool of GSH, which is relatively resistant to depletion by BSO. That the inhibition of full blast transformation is truly due to GSH depletion was proven by experiments in which GSH was repleted exogenously and a full blast transformation was restored. The results of previous work in our laboratory had shown that the sulfhydryl-reactive agent 2-cyclohexene-1-one (2-CHX) was a potent inhibitor of activation at soluble intracellular GSH concentrations well above 0.27 nmol/10(7) PBL. In the present study, the dose-dependent inhibition of activation by 2-CHX was confirmed, but it was shown that the degree of inhibition caused by 2-CHX could be at least partially dissociated from the level of intracellular GSH present at the time of lectin addition and that the inhibitory potential of 2-CHX exceeded that of BSO at comparable levels of soluble intracellular GSH. Thus, the inhibitory properties of 2-CHX cannot be accounted for solely on the basis of GSH depletion.

The Journal of Allergy and Clinical Immunology, Feb 1, 2023

PubMed, Sep 1, 1987

Allergic reactions can result from virtually any drug. In the pharmacopeia the possibility of an ... more Allergic reactions can result from virtually any drug. In the pharmacopeia the possibility of an allergic reaction to a drug must be considered in any instance when a patient reports an adverse effect to a drug. Although most allergic reactions to drugs are mild, they may be severe and at times fatal. Thus, it is imperative that every physician understand the spectra of drug allergy, the methods for diagnosing, and the means of treating allergic reactions to drugs. This review places drug allergies within the context of the over-all spectra of adverse reaction to drugs, defines the spectra of allergic reactions in terms of the organ systems involved and the severity of the reactions, suggests mechanisms for diagnosing drug allergy by historical evaluation, and where possible, by skin testing procedures and provocative dose challenges, and provides a variety of methods for reintroduction of drugs to which patients have been demonstrated to be allergic. The most important aspect of allergic reactions to drugs, however, is the understanding on the part of the physician that any drug has the potential for causing an allergic reaction and that extreme vigilance in terms of the diagnosis and treatment of these reactions is necessary.

Theophylline (1,3-dimethylxanthine) is a major mainstay in the treatment of asthma in the United ... more Theophylline (1,3-dimethylxanthine) is a major mainstay in the treatment of asthma in the United States. Originally introduced in 1937 and prescribed in combination with ephedrine (4:1 or 5:1) it is now clear that theophylline, or its more water soluble salts, alone is the appropriate dosage form.

The Journal of Allergy and Clinical Immunology, Feb 1, 2020

Pregnancy complications and outcomes in hereditary angioedema (HAE) patients have not been well c... more Pregnancy complications and outcomes in hereditary angioedema (HAE) patients have not been well characterized. Prevalence of pregnancy outcomes and obstetric complications were compared between pregnant women with and without HAE in a national US population. METHODS: A pooled retrospective cohort of pregnant women was identified within Truven Market Scan and Pharmetrics insurance claims databases from 2012-2017 using at least one claim for a pregnancy outcome. The HAE cohort was identified using a ICD-9 CM: 277.6/ ICD-10 CM: D84.1 diagnosis and/or HAE prescription claim codes. Each HAE patient was matched to 5 non-HAE patients by age, region, and health plan. Propensity score matching (PSM) was used to compare outcomes. RESULTS: A total of 227 HAE and 1,135 non-HAE patients with a mean age of 31.7 years comprised the study population. HAE patients had a significantly higher mean Quan-Charlson comorbidity index (0.39 vs. 0.16, p<0.0001) and a higher risk of having at least one pregnancy-related risk factor as compared to the non-HAE cohort (18.94% vs. 10.22%, p50.00002). After PSM, the HAE cohort had a significantly lower likelihood of having a singleton live birth (73.76% vs 82.18%, p50.0413) and higher frequency of premature rupture of membranes (9.41% vs 2.97%, p50.0073). There were no significant differences in other delivery outcomes, complications during pregnancy, or postpartum complications. CONCLUSIONS: Live births were significantly fewer among women with HAE, compared to women without HAE. Further investigations are required to explore the underlying reasons and the impact of the C1-INH deficiency status in the pathophysiology of maintaining a healthy pregnancy.

PubMed, Dec 1, 1979

SRS was generated from human leukemic basophils upon stimulation with ionophore A23187. Radiolabe... more SRS was generated from human leukemic basophils upon stimulation with ionophore A23187. Radiolabel from [14C]-AA was incorporated into SRS with continued comigration of radioactivity and bioactivity through several chromatographic systems including DEAE-cellulose, silicic acid, and RP-HPLC. Human basophilic leukemia SRS displayed physiochemical properties similar to those of rat basophilic leukemia cell SRS.

PubMed, May 1, 1979

When rat peritoneal mast cells were exposed to the ionophore A23187, a principle was released tha... more When rat peritoneal mast cells were exposed to the ionophore A23187, a principle was released that possessed the biologic properties of slow reacting substance (SRS) from various sources. The response was dose, time, and temperature dependent with no activity being demonstrated in unstimulated cells. Supporting evidence that the mast cell product was similar or identical to SRS obtained from other sources include: 1) appropriate differential bioassay profile, 2) resistance to lipolysis and proteolysis, 3) acid lability and base stability, 4) inactivation by limpet arylsulfatase, and 5) inhibition by low concentrations FPL 55712. These data demonstrate that the isolated rat peritoneal mast cell contains the biosynthetic capacity to produce a bioreactive substance with the properties of SRS.