Mark H. Wener

Bio: Mark H. Wener is an academic researcher from University of Washington Medical Center. The author has contributed to research in topics: Hepatitis C virus & Vaccination. The author has an hindex of 5, co-authored 7 publications receiving 161 citations.

Allogeneic marrow transplantation in patients with severe systemic sclerosis: resolution of dermal fibrosis.

Abstract: Systemic sclerosis (SSc) is a multisystem auto-immune disease in which the skin, lungs, heart, gastrointestinal (GI) tract, and kidneys are major targets of vasculopathy and progressive fibrosis. There is variability in the clinical manifestations, but patients with diffuse cutaneous SSc and involvement of internal organs often have a markedly reduced lifespan (1). For this study, it was hypothesized that allogeneic hematopoietic cell transplantation (HCT) could replace host autoreactive immune effector cells with donor-derived nonautoreactive cells and induce sustained remissions of SSc. As the methods for preventing infection and graft-versus-host disease (GVHD) have improved, the risks of transplant-related mortality and morbidity have diminished. Survival after allogeneic HCT for aplastic anemia, thalassemia, sickle cell disease, and chronic myelogenous leukemia in chronic phase have been reported to be between 85% and 95% (2–5). Preclinical studies of allogeneic HCT have been shown to be effective for the prevention or induction of sustained remissions in experimental models of auto-immune disease (6,7). Patients with autoimmune diseases who received transplants for other primary diseases have also experienced sustained remissions of the autoimmune disease (8). In the present study, 2 patients with poor-prognosis SSc were treated with allogeneic HCT. We describe their outcomes herein.

Variation in measurement of prostate-specific antigen: importance of method and lot variability.

Abstract: Equivalence between Hybritech Tandem and Abbott IMx PSA methods have been reported by some but not all previous investigators. To determine reasons for these differing conclusions, we measured serum PSA with three different lots each of IMx and Tandem-E kits. Overall, mean IMx results were significantly lower than Tandem-E results; however, for selected sera, the IMx results were consistently higher than the Tandem-E results. Lot-to-lot differences for the IMx method were significantly greater than those with the Tandem-E method. Most IMx/Tandem-E lot-to-lot comparisons had linear regression slopes that differed significantly from 1.0, but some did not. Conclusions concerning the equivalence of the IMx and the Tandem-E methods can be influenced both by variations in the proportions of free PSA in sera in tested populations and by lot-to-lot differences in the IMx method.

The direct embryotoxicity of immunoglobulin G fractions from patients with systemic lupus erythematosus.

Abstract: PROBLEM: To determine if IgG fractions from sera of individuals with systemic lupus erthymatosus (SLE) were toxic to cultures of whole rat embryos. METHODS: Head-fold stage rat embryos (9.5 days of gestation) were cultured on media consisting of 50% rat serum containing IgG fractions isolated from plasmapheresis plasma of six subjects with SLE and six with other autoimmune diseases. Each fraction was tested at 11 mg/ml and those toxic were also tested at 7.5 and 4 mg/ml. RESULTS: Of the six SLE IgG fractions, four were embryotoxic (embryolethal or teratogenic) while only one of the six non-SLE fractions were embryotoxic. CONCLUSION: IgG fractions from subjects with SLE can be toxic to cultures of whole rat embryos in the absence of maternal tissues or influence. Such cultures of whole embryos may be useful to identify those antibodies that represent a risk for fetal loss as well as to understand their mechanisms of embryotoxicity.

Analytical and clinical performance characteristics of Hybritech's Tandem-R free PSA assay during a large multicenter clinical trial to determine the clinical utility of percentage of free prostate-specific antigen

Abstract: Prostate-specific antigen (PSA) is present in serum in several forms, most importantly free PSA (FPSA) and PSA complexed to α1-antichymotrypsin (1)(2). These PSA forms are useful in assessing prostate disease (3)(4)(5). When PSA is >10 μg/L (ng/mL), the probability of prostate cancer is 50% (6); when PSA is between 4 and 10 μg/L, the probability of prostate cancer is 25%. Patients in the latter range are usually recommended for biopsy, but here the low specificity leads to many unnecessary biopsies. The percentage of FPSA (%FPSA) is used to enhance specificity. The relative proportion of FPSA in serum may range from 5% to 50% (7), but a lower %FPSA is associated with higher probability of prostate cancer (8). Published guidelines for the clinical use of %FPSA have been contradictory because of differences in assay systems and standardization, study designs, patient populations, and the number of subjects enrolled (9). A large well-controlled multicenter clinical trial was conducted to define a medically significant %FPSA cutpoint that would indicate the need for prostate biopsy. This report summarizes the assay performance from the largest clinical trial to date evaluating %FPSA in a patient population representative of those men in whom the test would be used in clinical practice. The data formed the basis for the Food and Drug Administration’s approval of Hybritech’s free PSA assays. Detailed clinical performance characteristics have been presented previously (10). The objective of this clinical trial was twofold: to evaluate the performance of Hybritech’s Tandem®-R free PSA assay as it is routinely used in laboratories, and to identify a %FPSA cutpoint with a high rate of cancer detection (clinical sensitivity) while avoiding unnecessary biopsies in men without …

Prenatal Infection and Schizophrenia: A Review of Epidemiologic and Translational Studies

Abstract: An emerging literature from epidemiologic, clinical, and preclinical investigations has provided evidence that gestational exposure to infection contributes to the etiology of schizophrenia. In recent years, these studies have moved from ecologic designs, which ascertain infection based on epidemics in populations, to investigations that have capitalized on reliable biomarkers in individual pregnancies. These studies have documented specific candidate infections that appear to be associated with an elevated risk of schizophrenia. Animal models of maternal immune activation inspired by this work have revealed intriguing findings indicating behavioral, neurochemical, and neurophysiologic abnormalities consistent with observations in schizophrenia. In parallel studies in humans and animals, investigators are working to uncover the cellular and molecular mechanisms by which in utero exposure to infection contributes to schizophrenia risk. In this review, the authors discuss and critically evaluate the...

Maternal Exposure to Toxoplasmosis and Risk of Schizophrenia in Adult Offspring

Abstract: OBJECTIVE: The authors examined the relationship between maternal antibody to toxoplasmosis and the risk of schizophrenia and other schizophrenia spectrum disorders in offspring. Toxoplasmosis is known to adversely affect fetal brain development. METHOD: In a nested case-control design of a large birth cohort born between 1959 and 1967, the authors conducted serological assays for Toxoplasma antibody on maternal serum specimens from pregnancies giving rise to 63 cases of schizophrenia and other schizophrenia spectrum disorders and 123 matched comparison subjects. Toxoplasma immunoglobulin (Ig)G antibody was quantified by using the Sabin-Feldman dye test. The Ig titers were classified into three groups: negative (<1:16) (reference), moderate (1:16–1:64), and high (≥1:128). RESULTS: The adjusted odds ratio of schizophrenia/schizophrenia spectrum disorders for subjects with high maternal Toxoplasma IgG antibody titers was 2.61 (95% confidence interval=1.00–6.82). There was no association between moderate Tox...

Clinical Applications of Blood-Derived and Marrow-Derived Stem Cells for Nonmalignant Diseases

Abstract: Context Stem cell therapy is rapidly developing and has generated excitement and promise as well as confusion and at times contradictory results in the lay and scientific literature. Many types of stem cells show great promise, but clinical application has lagged due to ethical concerns or difficulties in harvesting or safely and efficiently expanding sufficient quantities. In contrast, clinical indications for blood-derived (from peripheral or umbilical cord blood) and bone marrow–derived stem cells, which can be easily and safely harvested, are rapidly increasing. Objective To summarize new, nonmalignant, nonhematologic clinical indications for use of blood- and bone marrow–derived stem cells. Evidence Acquisition Search of multiple electronic databases (MEDLINE, EMBASE, Science Citation Index), US Food and Drug Administration [FDA] Drug Site, and National Institutes of Health Web site to identify studies published from January 1997 to December 2007 on use of hematopoietic stem cells (HSCs) in autoimmune, cardiac, or vascular diseases. The search was augmented by hand searching of reference lists in clinical trials, review articles, proceedings booklets, FDA reports, and contact with study authors and device and pharmaceutical companies. Evidence Synthesis Of 926 reports identified, 323 were examined for feasibility and toxicity, including those with small numbers of patients, interim or substudy reports, and reports on multiple diseases, treatment of relapse, toxicity, mechanism of action, or stem cell mobilization. Another 69 were evaluated for outcomes. For autoimmune diseases, 26 reports representing 854 patients reported treatment-related mortality of less than 1% (2/220 patients) for nonmyeloablative, less than 2% (3/197) for dose-reduced myeloablative, and 13% (13/100) for intense myeloablative regimens, ie, those including total body irradiation or high-dose busulfan. While all trials performed during the inflammatory stage of autoimmune disease suggested that transplantation of HSCs may have a potent disease-remitting effect, remission duration remains unclear, and no randomized trials have been published. For reports involving cardiovascular diseases, including 17 reports involving 1002 patients with acute myocardial infarction, 16 involving 493 patients with chronic coronary artery disease, and 3 meta-analyses, the evidence suggests that stem cell transplantation performed in patients with coronary artery disease may contribute to modest improvement in cardiac function. Conclusions Stem cells harvested from blood or marrow, whether administered as purified HSCs or mesenchymal stem cells or as an unmanipulated or unpurified product can, under appropriate conditions in select patients, provide disease-ameliorating effects in some autoimmune diseases and cardiovascular disorders. Clinical trials are needed to determine the most appropriate cell type, dose, method, timing of delivery, and adverse effects of adult HSCs for these and other nonmalignant disorders.