Cell Biology Commons^™

Prostate Specific Membrane Antigen (Psma): Immunoassay Development And Characterization Of Transcriptional Regulation, Zhen Xiao

Theses and Dissertations in Biomedical Sciences

Prostate cancer (PCA) is the most common cancer and the second leading cause of death among American men. The high mortality is greatly attributed to the lack of early detection tools and effective treatment for metastasis and relapses. Biomarkers that can discriminate benign from malignant tumor and signal the development of androgen independent and metastatic tumor are needed. A biomarker designated prostate specific membrane antigen (PSMA) has the potential to fulfill this need. The objective of this study is to develop a clinically useful immunoassay for quantitation of serum PSMA and to study the molecular mechanism underlying the upregulation of …

Improved Energy Model For Membrane Electroporation In Biological Cells Subjected To Electrical Pulses, R. P. Joshi, Q. Hu, K. H. Schoenbach, H. P. Hjalmarson

Bioelectrics Publications

A self-consistent model analysis of electroporation in biological cells has been carried out based on an improved energy model. The simple energy model used in the literature is somewhat incorrect and unphysical for a variety of reasons. Our model for the pore formation energy E(r) includes a dependence on pore population and density. It also allows for variable surface tension, incorporates the effects of finite conductivity on the electrostatic correction term, and is dynamic in nature. Self-consistent calculations, based on a coupled scheme involving the Smoluchowski equation and the improved energy model, are presented. It is shown that E(r) becomes …

Receptor Number And Caveolar Co-Localization Determine Receptor Coupling Efficiency To Adenylyl Cyclase, Rennolds S. Ostrom, Caroline Gregorian, Ryan M. Drenan, Yang Xiang, John W. Regan, Paul A. Insel

Pharmacy Faculty Articles and Research

Recent evidence suggests that many signaling molecules localize in microdomains of the plasma membrane, particularly caveolae. In this study, overexpression of adenylyl cyclase was used as a functional probe of G protein-coupled receptor (GPCR) compartmentation. We found that three endogenous receptors in neonatal rat cardiomyocytes couple with different levels of efficiency to the activation of adenylyl cyclase type 6 (AC6), which localizes to caveolin-rich membrane fractions. Overexpression of AC6 enhanced the maximal cAMP response to β1-adrenergic receptor (β1AR)-selective activation 3.7-fold, to β2AR-selective activation only 1.6-fold and to prostaglandin E2 (PGE2) not at all. Therefore, the rank order of efficacy in …

Induction Of Apoptosis In Human Prostate Cancer Cells By Resveratrol, Gary Zulfikar Morris

Chemistry & Biochemistry Theses & Dissertations

Recently attention has been brought to trans-resveratrol's {TR) anticancer activity, as determined through a number of cultured cancer cell models. This activity was attributed to TR behaving as an estrogen, and the orientation of TR' s hydroxyl groups. Based on this work it was of interest to determine whether TR would also be toxic in prostate cancer cells; if toxic, did TR induce necrosis or apoptosis in the cells; was it toxic through hormone mediated pathways; and were TR's hydroxyl groups responsible for its biological activity. To this end, cellular viability was assessed in two different prostate cancer cell …

An Ultrastructural Survey Of The Nuchal Glands Of Rhabdophis Tigrinus (Serpentes: Colubridae), Kathleen A. Roberts

Biological Sciences Theses & Dissertations

Rhabdophis tigrinus, an Asian natricine snake, possesses a series of integumentary glands located in the nuchal skin. Previous studies indicated that the nuchal glands are of mesodermal origin, contain cardiac steroids analogous to bufotoxins found in the parotoid glands of toads, which are included in the snake's diet. The nuchal glands are defensive in function. Preliminary histological studies revealed differences in quality of the gland tissue compared to previous studies, and difference in fixation techniques were suspected. Seven specimens of R. tigrinus were fixed by perfusion using a conservative fixation process standard for electron microscopy. The nuchal gland series …

Whole Animal And Cellular Strategies In The Regulation Of Bone Mass In The Rat, Weidong Geng

Theses, Dissertations and Capstones

In order to determine the strategies in regulation of bone mass in the rat and better understand the pathophysiological mechanism of the postmenopausal osteoporosis, a series of studies were conducted at the whole animal and cellular level. At the whole animal level, female Sprague-Dawley rats were ovariectomized (Ovx) or sham-operated (control) at 18 weeks and the entire skeleton obtained at 24 weeks (baseline) or after an additional 31 day (28 week) interval on a normal (1.0%) or deficient (0.02%) calcium diet. Ovx rats on the normal calcium diet showed a 42% increase in whole body bone resorption and a 70% …

The Skn7 Response Regulator Of Saccharomyces Cerevisiae Interacts With Hsf1 In Vivo And Is Required For The Induction Of Heat Shock Genes By Oxidative Stress, Desmond C. Raitt, Anthony L. Johnson, Alexander M. Erkine, Kozo Makino, Brian Morgan, David S. Gross, Leland H. Johnston

Scholarship and Professional Work – COPHS

The Skn7 response regulator has previously been shown to play a role in the induction of stress-responsive genes in yeast, e.g., in the induction of the thioredoxin gene in response to hydrogen peroxide. The yeast Heat Shock Factor, Hsf1, is central to the induction of another set of stress-inducible genes, namely the heat shock genes. These two regulatory trans-activators, Hsf1 and Skn7, share certain structural homologies, particularly in their DNA-binding domains and the presence of adjacent regions of coiled-coil structure, which are known to mediate protein–protein interactions. Here, we provide evidence that Hsf1 and Skn7 interact in vitro and …

Cell Cycle-Dependent Binding Of Yeast Heat Shock Factor To Nucleosomes, Christina Bourgeois Venturi, Alexander M. Erkine, David S. Gross

Scholarship and Professional Work – COPHS

In the nucleus, transcription factors must contend with the presence of chromatin in order to gain access to their cognate regulatory sequences. As most nuclear DNA is assembled into nucleosomes, activators must either invade a stable, preassembled nucleosome or preempt the formation of nucleosomes on newly replicated DNA, which is transiently free of histones. We have investigated the mechanism by which heat shock factor (HSF) binds to target nucleosomal heat shock elements (HSEs), using as our model a dinucleosomal heat shock promoter (hsp82-ΔHSE1). We find that activated HSF cannot bind a stable, sequence-positioned nucleosome in G₁-arrested …

Cellular Release Of And Response To Atp As Key Determinants Of The Set-Point Of Signal Transduction Pathways, Rennolds S. Ostrom, Caroline Gregorian, Paul A. Insel

Pharmacy Faculty Articles and Research

The determinants of “basal” activity of signaling pathways regulating cellular responses are poorly defined. One possibility is that cells release factors to establish the set-point of such pathways. Here we show that treatment of Madin-Darby canine kidney cells with the nucleotidase apyrase decreases basal arachidonic acid release and cAMP production 30–40% and that inhibitors of P2Y receptor action also affect basal and forskolin-stimulated cAMP accumulation. Changing medium prominently increases extracellular levels of ATP in Madin-Darby canine kidney, COS-7, and HEK-293 cells. Mechanical stimulation of ATP release likely occurs in virtually every experimental protocol with cultured cells, implicating such release and …

Telomerase Activity In Human Preimplantation Embryos, Diane Lynne Wright

Theses and Dissertations in Biomedical Sciences

Telomerase, a ribonucleoprotein, has been described as an essential component of highly proliferative cells, which stabilizes the telomeres and avoids cellular senescence. Telomerase has been identified in various embryonic cell stages, hematopoietic cells, and in >85% of tumor tissue biopsies analyzed. The ability to measure the potential to proliferate successfully could provide an objective measure of an embryo's quality. The objectives of this study were to modify the telomeric repeat amplification protocol (TRAP) assay system for increased sensitivity to allow detection of telomerase activity in the single cell of an oocyte and embryo, obtain telomerase activity levels for the oocyte …

Identification And Characterization Of Determinants Of Head And Neck Tumor Cell Invasion, Yangguan Wu

Theses and Dissertations in Biomedical Sciences

Head and neck squamous cell carcinoma (HNSCC) is a common malignant disease with poor prognosis. The majority of patients die from local invasion or lymphatic metastasis. The mechanism(s) underlining the invasiveness of HNSCC are poorly understood. Utilizing a panel of HNSCC cell lines previously established in our laboratory, we tested the application and relevance of the three-step hypothesis of tumor invasion to HNSCC and investigated the mechanism(s) pertaining to the regulation of each step in the invasive process. Data presented in this thesis demonstrated that tumor cell invasion in HNSCC is a complex process involving three repeated sequential steps: adhesion, …

Insulinlike Growth Factor 1- And 2-Augmented Collagen Gel Repair Of Facial Osseous Defects, James S. Toung, Roy C. Ogle, Raymond F. Morgan, William H. Lindsey

School of Medical Diagnostics & Translational Sciences Publications

BACKGROUND: Defects of the facial bone structure are common problems for the facial plastic surgeon. Native type 1 collagen gels (T1CGs) have been shown to mediate repair of facial critical-size defects in rat models.

OBJECTIVE: To evaluate the efficacy of T1CG augmented with insulinlike growth factor (IGF) 1, IGF-2, and a combination of IGF-1 and IGF-2 on the repair of facial critical-size defects in a rodent model.

METHODS: Twenty-four retired male breeder Sprague-Dawley rats were divided into 4 groups of 6 animals. Facial critical-size defects were created by removing the nasalis bones with a bone-cutting drill. Defects were treated with …

Interaction Of Laminin Beta2 With Eps8 And Desmin In Muscle Cells, Luke Xueliang Cui

Theses, Dissertations and Capstones

Laminin β2 is localized to the synaptic basal lamina (BL) in muscle and glomerular BL in kidney. To find interacting proteins, a mouse kidney cDNA library was screened with domain I of rat laminin β2 using the yeast two-hybrid system. Fifteen positive clones were found. The DNA sequence of three each of these clones corresponded to the phosphoprotein Eps8 (epidermal growth factor receptor pathway substrate clone 8, which is tyrosine phosphorylated after EGF stimulation) and the intermediate filament (IF) protein keratin. To determine if this interaction occurred in muscle cells, C2 cells transfected with the rat …

Cooperative Binding Of Heat Shock Factor To The Yeast Hsp82 Promoter In Vivo And In Vitro, Alexander M. Erkine, Serena F. Magrogan, Edward A. Sekinger, David S. Gross

Scholarship and Professional Work – COPHS

revious work has shown that heat shock factor (HSF) plays a central role in remodeling the chromatin structure of the yeastHSP82 promoter via constitutive interactions with its high-affinity binding site, heat shock element 1 (HSE1). The HSF-HSE1 interaction is also critical for stimulating both basal (noninduced) and induced transcription. By contrast, the function of the adjacent, inducibly occupied HSE2 and -3 is unknown. In this study, we examined the consequences of mutations in HSE1, HSE2, and HSE3 on HSF binding and transactivation. We provide evidence that in vivo, HSF binds to these three sites cooperatively. This cooperativity is seen …

Inhibition Of Cpla2-Mediated Arachidonic Acid Release By Cyclic Amp Defines A Negative Feedback Loop For P2y-Receptor Activation In Mdck-D1 Cells, Mingzhao Xing, Steven Post, Rennolds S. Ostrom, Michael Samardzija, Paul A. Insel

Pharmacy Faculty Articles and Research

In Madin-Darby canine kidney D1cells extracellular nucleotides activate P2Y receptors that couple to several signal transduction pathways, including stimulation of multiple phospholipases and adenylyl cyclase. For one class of P2Y receptors, P2Y2 receptors, this stimulation of adenylyl cyclase and increase in cAMP occurs via the conversion of phospholipase A2 (PLA2)-generated arachidonic acid (AA) to prostaglandins (e.g. PGE2). These prostaglandins then stimulate adenylyl cyclase activity, presumably via activation of prostanoid receptors. In the current study we show that agents that increase cellular cAMP levels (including PGE2, forskolin, and the β-adrenergic agonist isoproterenol) can inhibit P2Y receptor-promoted AA release. The protein kinase …

Efficacy Of AllowashTm Solution In Solubilization Of Bone Marrow, Alyce Marie Linthurst

Biological Sciences Theses & Dissertations

LifeNet currently cleans allograft bone utilizing Allowash^TM Technology, which encompasses the use of a closed continuous circulation chamber to remove bone marrow by flushing it with Allowash^TM Solution for a prescribed time and temperature after which, it is rinsed with various solutions to remove residual detergent that could be toxic to the recipient. A portion of this process employs Allowash^TM Solution to improve the solubilization and removal of protein and cellular elements in the red bone marrow. This study examines the effectiveness of Allowash^TM Solution in comparison to its component detergents Nonidet P40, Nonoxynol 9 and …

The Role Of Glycoconjugates In Mediating Human Fertilization And Induction Of Fetomaternal Tolerance, Manish S. Patankar

Theses and Dissertations in Biomedical Sciences

Using the hemizona assay (HZA), a in vitro sperm-egg binding assay, we show that specific glycoconjugates known to inhibit immune cell interactions mediated by the selectins, potently block human sperm-egg binding. The selectin ligand sialyl Lewis^x inhibits sperm binding in the HZA by 60% at a concentration of 1 mg/ml. Our data indicates that glycodelin-A, a endometrial glycoprotein known to block sperm-egg binding in the HZA at low concentrations expresses unusual fucosylated lacdiNAc type glycans. The fucosylated lacdiNAc type sugars have been previously shown to be 15-20 fold more potent ligands of E-selectin. Glycodelin-S a seminal plasma glycoform of …

Reaction-Diffusion Models Of Cancer Dispersion, Kim Yvette Ward

Mathematics & Statistics Theses & Dissertations

The phenomenological modeling of the spatial distribution and temporal evolution of one-dimensional models of cancer dispersion are studied. The models discussed pertain primarily to the transition of a tumor from an initial neoplasm to the dormant avascular state, i.e. just prior to the vascular state, whenever that may occur. Initiating the study is the mathematical analysis of a reaction-diffusion model describing the interaction between cancer cells, normal cells and growth inhibitor. The model leads to several predictions, some of which are supported by experimental data and clinical observations $\lbrack25\rbrack$. We will examine the effects of additional terms on these characteristics. …

Pressure-Induced Intracellular Signaling In Isolated Arteries, Victor A. Miriel

Theses and Dissertations in Biomedical Sciences

The ability of cells to respond to mechanical stimuli has been studied through a variety of techniques in numerous cell types. The cells of the vascular wall have adapted to specific mechanical stresses through the activation of intracellular signaling pathways which result in cell-specific responses such as hypertrophy, hyperplasia, proliferation, and migration. Vascular smooth muscle of the arteries have been shown to be sensitive to mechanical stimuli such as stretch, and pressure.

This study attempts to add to the current knowledge of mechanotransduction by utilizing the isolated artery preparation. This preparation allows for the study of vascular smooth muscle signal …

Alterations In Calcium Homeostasis And The Insulin-Like Growth Factor Signaling Pathway Induced By Carcinogenic Polycyclic And Halogenated Aromatic Hydrocarbons In Human Mammary Epithelial Cells, Stacey L. Tannheimer

Pharmaceutical Sciences ETDs

Breast cancer is a major health concern for women, with only a small percent of the risk factors currently identified. It has been estimated that environmental factors may contribute to up to 80% of breast cancer cases. Many environmental carcinogens, such as polycyclic and halogenated aromatic hydrocarbons (PAHs and HAHs), are proven mammary carcinogens in animal models. Therefore, these studies were conducted to elucidate potential roles of PAHs and HAHs in alterations in known signaling pathways in human mammary epithelial cells (HMEC). Carcinogenic PAHs have previously been shown to produce sustained alterations in the calcium (Ca2') homeostasis of lymphocytes Therefore, …

Comparison Of Beta-Adrenoceptor Coupled Camp Production In Cultured Human Mononuclear Leukocytes And Myometrial Cells, Yu-Li Liu

Electronic Theses and Dissertations

$\beta\sb2$-Adrenoceptor ($\beta\sb2$-AR) agonists, such as terbutaline, are used as tocolytic agents in the treatment of preterm labor. $\beta$-Adrenoceptor stimulation relaxes myometrium through specific receptors coupled through Gs to adenylyl cyclase (AC) that catalyzes the conversion of ATP to cAMP. The purpose of this study was to compare $\beta$-adrenoceptors and cAMP production in cultured human leukocytes and myometrial cells, and to determine the importance of $\beta$-adrenoceptors and cAMP production in isoproterenol-induced myometrial relaxation. $\sp{125}$I-iodopindolol was used to assess $\beta$-adrenoceptor affinity and number cAMP levels were analyzed before and after stimulation by isoproterenol, AlF$\sb4\sp-$, forskolin, and PGE$\sb1$. Isometric recording was used to …

Alterations In Human B Cell Calcium Homeostasis By Polycyclic Aromatic Hydrocarbons: Possible Associations With Cytochrome P450 Metabolism And Increased Tyrosine Phosphorylation, Barbara J. Mounho

Pharmaceutical Sciences ETDs

Polycyclic aromatic hydrocarbons (PAHs), are known immunotoxicants in animals, and are suspect toxins to the human immune system. The mechanism(s), however, by which PAHs exert immunosuppression have not been fully elucidated. Previous studies conducted in our laboratory have shown that PAHs, such as 7,12-dimethylbenz(a)- anthracene (DMB A) and benzo(a)pyrene (BaP) may exert their immunotoxic effects by altering intracellular calcium (Ca2+) homeostasis in lymphocytes. Intracellular Ca2+ is an important second messenger in the immune response, and the mobilization of Ca2+ is critical in the transduction of intracellular signals from the plasma membrane to the nucleus. The overall objective of this project …

A Heterodimer Of Thioredoxin And Ib2 Cooperates With Sec18p (Nsf) To Promote Yeast Vacuole Inheritance, Zuoyu Xu, Andreas Mayer, Eric Muller, William Wickner

Dartmouth Scholarship

Early in S phase, the vacuole (lysosome) of Saccharomyces cerevisiae projects a stream of vesicles and membranous tubules into the bud where they fuse and establish the daughter vacuole. This inheritance reaction can be studied in vitro with isolated vacuoles. Rapid and efficient homotypic fusion between saltwashed vacuoles requires the addition of only two purified soluble proteins, Sec18p (NSF) and LMA1, a novel heterodimer with a thioredoxin subunit. We now report the identity of the second subunit of LMA1 as IB2, a previously identified cytosolic inhibitor of vacuolar proteinase B. Both subunits are needed for efficient vacuole inheritance in vivo …

Interleukin-2 Fusion Protein: An Investigational Therapy For Interleukin-2 Receptor Expressing Malignancies, Jean Nichols, Foss Francine, Kuzel Timothy, Lemaistre Charles Fred, Platanias Leonidas, Ratain Mark, Rook Alain, Mansoor Saleh, Schwartz Gary

Haematology and Oncology, East Africa

DAB3s91L-2 is an interleukin-2 receptor (IL-2R) specific fusion protein with a molecular weight of 58 kD containing the enzymatic and translocation domains of diphtheria toxin (DT) and human IL-2. This fusion protein is able to direct the cytocidal action of the DT enzymatic region only to cells which bear the IL-2R. The human IL-2R exists in three forms: low, intermediate and high affinity. The high-affinity form is believed to be the biologically relevant form on mature, activated T-lymphocytes, B-lymphocytes and monocytes. DAB3sgIL-2 is able to bind selectively to the high-affinity IL-2R in a concentration-dependent manner, and once bound is internalised …

Heat Shock Factor Gains Access To The Yeast Hsc82 Promoter Independently Of Other Sequence-Specific Factors And Antagonizes Nucleosomal Repression Of Basal And Induced Transcription, Alexander M. Erkine, C. C. Adams, T. Diken, D. S. Gross

Scholarship and Professional Work – COPHS

Transcription in eukaryotic cells occurs in the context of chromatin. Binding of sequence-specific regulatory factors must contend with the presence of nucleosomes for establishment of a committed preinitiation complex. Here we demonstrate that the high-affinity binding site for heat shock transcription factor (HSF) is occupied independently of other cis-regulatory elements and is critically required for preventing nucleosomal assembly over the yeast HSC82 core promoter under both noninducing (basal) and inducing conditions. Chromosomal mutation of this sequence, termed HSE1, erases the HSF footprint and abolishes both transcription and in vivo occupancy of the TATA box. Moreover, it dramatically reduces promoter chromatin …

Phase Ia/Ib Trial Of Anti-Gd2 Chimeric Monoclonal Antibody 14.18 (Ch L4.18) And Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor (Rhgm-Csf) In Metastatic Melanoma, James Murray, Eugenie Kleinerman, Shu-Fang Jia, Michael Rosenblum, Omar Eton, Antonio Buzaid, Sewa Legha, Merrick Ross, Lora Thompson, Mansoor Saleh

Haematology and Oncology, East Africa

We performed a phase Ia/Ib trial of chimeric anti-GD2 monoclonal antibody 14.18 (ch14.18) in combination with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) to determine the maximum tolerated dose as well as immunologic and biologic responses to the regimen. Sixteen patients with metastatic malignant melanoma received escalating doses of ch14.18 (15-60 mg/m2) administered intravenously for 4 h on day 1. Twenty-four hours later, subcutaneous injections of rhGM-CSF were administered daily for a total of 14 days. Significant side effects were related to ch14.18 infusion and consisted of moderate to severe abdominal and/or extremity pain, blood pressure changes, headache, nausea, diarrhea, peripheral …

In Vitro Expression Of Human Zona Pellucida Protein 3, Chih-Wei Chen

Theses and Dissertations in Biomedical Sciences

Human zona pellucida protein 3 (hZP3) is the putative receptor on the zona pellucida of the mature oocyte that recognizes and binds sperm, and therefore plays a critical role in fertilization.

A full length cDNA of hZP3 (1278 bp) was amplified from the human ovary mRNA by reverse transcription-polymerase chain reaction (RT-PCR). The hZP3 cDNA was subcloned into PSK and pREP4 expression vectors. The cDNA of hZP3 was further characterized by restriction mapping, PCR, auto-sequencing and Southern blot analysis by using an internal oligonucleotide probe, and found to be identical to the one reported by J. Dean. Using autosequencing, 289 …

A Kinetic Investigation Of The Mechanism Of Muscle Contraction With A Series Of Nucleotides, Wei Jiang

Theses and Dissertations in Biomedical Sciences

Muscle contraction is thought to be accomplished by sliding of myosin filaments along actin filaments. Although actomyosin naturally uses ATP as an energy source, it can also use other nucleoside triphosphates (NTP) as substrates. In this work, the dependence of rate and equilibrium constants of the various steps in the muscle contraction mechanism upon nucleotide structure was investigated to unravel the dependence of the mechanical properties of the muscle upon changes in different biochemical steps of the mechanism.

The experiments measuring the dissociation of actomyosin by NTP (or mant-NTP) shows that both the rate constant of actomyosin-S1 dissociation and second …

Phase Ii Trial Of Murine Monoclonal Antibody D612 Combined With Recombinant Human Monocyte Colony-Stimulating Factor (Rhm-Csf) In Patients With Metastatic Gastrointestinal Cancer, Mansoor Saleh, Michael Khazaeli, Richard Wheeler, Pat Bucy, Tiepe Liu, Michael Everson, David Mun, Jeff Schlom

Haematology and Oncology, East Africa

In a Phase II study, 14 patients with metastatic gastrointestinal cancer received the mAb D612 (40 mg/m2, days 4, 7, and 11) in combination with recombinant human monocyte colony-stimulating factor [(rhM-CSF) 80 ug/kg/days 1-14]. The combined treatment was well tolerated and resulted in characteristic biological activity associated with each of the agents. Thus, 10 of 14 patients experienced D612-associated secretory diarrhea, which responded to the prostaglandin inhibitor Indomethacin in 5 of 7 patients. rhM-CSF therapy was associated with peripheral mono- cytosis (peak absolute monocyte count, 1444 ±394/mm3) and thrombocytopenia (nadir count, 78 ±10/nim '). Monocyte surface marker analysis revealed a …

Cd16+ Monocytes In Patients With Cancer: Spontaneous Elevation And Pharmacologic Induction By Recombinant Human Macrophage Colony- Stimulating Factor, Mansoor Saleh, Goldman Samuel, Lobuglio Albert, Beall Arthur, Sabio Hernan, Mccord Melissa, Minasian Lori, Alpaugh Katherine, Weiner Louis, Munn David

Haematology and Oncology, East Africa

The small subset of circulating monocytes that express the maturation- associated CD16 antigen has recently been reported to be elevated in patients with bacterial sepsis. We now show that this novel CD16+ monocyte population is also spontaneously expanded in patients with cancer. We studied 14 patients with metastatic gastrointestinal carcinoma enrolled in a clinical trial of recombinant human macrophage colony-stimulating factor (rhMCSF) plus monoclonal antibody D612. We found that before any cytokine treatment, 12 of 14 patients constitutively displayed significant elevations in both the percentage and the absolute number of CD16+ monocytes, as compared with both normal subjects and ill …