Eva Mezey

• MD, PhD
• Head of Department at National Institutes of Health

Our knowledge of which bone marrow cells affect red cell production is still incomplete. To explore the role of osteocytes in the process we performed bulk RNAseq of osteocytes isolated from control and phlebotomized mice. The top-upregulated gene following phlebotomy was Fam132b, erythroferrone (Erfe). Erfe expression in osteocytes was also upregu...

G-protein coupled receptors (GPCRs) are encoded by nonabundant mRNAs, and it is difficult to detect them reliably with the highly parallel methods that are in general use. Because of this, we developed and validated a sensitive, specific, semi-quantitative method for detecting these transcripts. We have used the method to profile GPCR transcripts i...

Bone marrow stromal cells (BMSCs) have immunomodulatory activities in numerous species and have been used in clinical trials. BMSCs also make antibacterial agents. Since hepcidin is known to have antimicrobial effects in fish, we wondered if it might also be used as an antimicrobial agent by mammalian BMSCs. In the present study, we show hepcidin e...

Adoptive transfer of cultured BMSCs was shown to be immune-suppressive in various inflammatory settings. Many factors play a role in the process, but no master regulator of BMSC-driven immunomodulation was identified. Consequently, an assay that might predict BMSC product efficacy is still unavailable. Below, we show that BMSC donor variability can...

Introduction: Preeclampsia (PE) is a pregnancy-related disorder associated with maternal hypertension and placental dysfunction. A significant micronutrient during pregnancy is iron, which is important in cellular functions. While iron absorption increases in pregnancy, little is known about the exact mechanisms regulating maternal iron levels and...

Background Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections result in the temporary loss of smell and taste in about one third of confirmed cases. Methods We used immunohistochemistry to confirm the presence of ACE2, NRP1 and TMPRSS2 in two cranial nerves (IX and X) that mediate taste where they leave/join the medulla. Sampl...

Studies of mesenchymal stem (or stromal) cells (MSCs) have moved from bedside to bench and back again. The stromal cells or fibroblasts are found in all tissues and participate in building the extracellular matrix (ECM). Bone marrow (BM)-derived MSCs have been studied for more than 50 years and have multiple roles. They function as stem cells and g...

Multiplex immunofluorescence (mIF) is an effective technique for the maximal visualization of multiple target proteins in situ. This powerful tool is mainly limited by the spectral overlap of the currently available synthetic fluorescent dyes. The fluorescence excitation wavelengths ranging between 405 and 488 nm are rarely used in mIF imaging and...

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) infections result in the temporary loss of smell and taste (anosmia and dysgeusia) in about one third of confirmed cases. Several investigators have reported that the viral spike protein receptor is present in olfactory neurons. However, no study has been published to date showing the prese...

The architecture of a biologic response is inextricably linked with the tissue architecture of the target site. Multiplex immunofluorescence (mIF) is an effective technique for the maximal visualization of multiple target proteins in situ. This powerful tool is limited by the spectral overlap separation of the currently available synthetic fluoresc...

Adult erythropoiesis is a highly controlled sequential differentiation of hematopoietic stem cells (HSCs) to mature red blood cells in the bone marrow (BM). The bones which contain BM are diverse in their structure, embryonic origin, and mode of ossification. This has created substantial heterogeneity in HSCs function in BM of different bones, howe...

Preeclampsia (PE) is a pregnancy disorder associated with placental dysfunction and elevated fetal hemoglobin (HbF). Early in pregnancy the placenta harbors hematopoietic stem and progenitor cells (HSPCs) and is an extramedullary source of erythropoiesis. However, globin expression is not unique to erythroid cells and can be triggered by hypoxia. T...

Significance The connection between brain and peripheral lymphatics has been studied for 250 y, mainly in animals. Specific markers for lymphatic endothelial cells (LECs) were discovered about a decade ago. We stained postmortem human brains with LYVE1 and PDPN to identify LECs. Marker-positive cells were found in membranes covering the brain, wall...

This study shows that melanoma-associated fibroblasts (MAFs) suppress cytotoxic T lymphocyte (CTL) activity and reveals a pivotal role played by arginase in this phenomenon. MAFs and normal dermal fibroblasts (DFs) were isolated from surgically resected melanomas and identified as Melan-A-/gp100-/FAP+ cells. CTLs of healthy blood donors were activa...

Sarcoidosis is a devastating inflammatory disease affecting many organs, especially the lungs and lymph nodes. Bone marrow-derived mesenchymal stromal cells (MSCs) can “reprogram” various types of macrophages towards an anti-inflammatory phenotype. We wanted to determine whether alveolar macrophages from sarcoidosis subjects behave similarly by mou...

Preeclampsia (PE) has been associated with placental dysfunction, resulting in fetal hypoxia, accelerated erythropoiesis, and increased erythroblast count in the umbilical cord blood (UCB). Although the detailed effects remain unknown, placental dysfunction can also cause inflammation, nutritional, and oxidative stress in the fetus that can affect...

Bone marrow–derived stromal cells or mesenchymal stromal cells (BMSCs or MSCs, as we will call them in this work) are multipotent progenitor cells that can differentiate into osteoblasts, adipocytes and chondrocytes. In addition, MSCs have been shown to modulate the function of a variety of immune cells. Donor age has been shown to affect the regen...

Background aims: Bone marrow-derived mesenchymal stromal cells (MSCs) have been reported to suppress T-cell proliferation and used to alleviate the symptoms of graft-versus-host disease (GVHD). MSCs are a mixed cell population and at this time there are no tools to isolate the cells responsible for the T-cell suppression. We wanted to find a way t...

Objective: In women with postmenopausal osteoporosis, vitamin K2 appears to decrease the incidence of hip, vertebral, and non-vertebral fractures. Women with postmenopausal osteoporosis have more circulating activated T cells compared with healthy postmenopausal and premenopausal women, but the effects of vitamin K2 on T cells have not been studie...

This unit presents protocols to locate RNA transcripts in tissues. Numerous approaches are detailed, including those that use radiolabeled or colorimetric probes. Also, the probes may be modified oligodeoxynucleotides, singly or in pairs, as well as ribonucleic acids. High sensitivity and specificity are obtained, especially with sets of oligodeoxy...

Arginine vasopressin (AVP) made by hypothalamic neurons is released into the circulation to stimulate water resorption by the kidneys and restore water balance after blood loss. Patients who lack this antidiuretic hormone suffer from central diabetes insipidus. We observed that many of these patients were anemic and asked whether AVP might play a r...

Introduction Preeclampsia (PE) is a pregnancy related disorder that affects 3–8% of pregnancies worldwide. Enhanced levels of free hemoglobin have been reported early in pregnancy in the maternal circulation as well as in term placentas in PE. The first stage of PE is associated with decreased trophoblast invasion into the spiral arteries, leading...

All living tissues require essential nutrients such as amino acids, fatty acids, carbohydrates, minerals, vitamins, and water. The skeleton requires nutrients for development, maintaining bone mass and density. If the skeletal nutritional requirements are not met, the consequences can be quite severe. In recent years, there has been growing interes...

In this issue of Blood , [Garcia-Montero et al][1][1][2] reported that in nearly 30% of patients with indolent systemic mastocytosis (SM), the characteristic c-kit mutation D816V,[2][3] is not restricted to mast cells, but may also be found in bone marrow (BM)–derived mesenchymal stem cells (MSCs

Faiyaz Notta and his colleagues from Dr. John Dick's group in Canada recently published an elegant study of blood cell development in Science (Notta et al., 2015)otta et al., 2015). Their data suggest that a different model from the prevailing one may explain the origin of diverse cells found in blood. This involves hematopoiesis, a term derived fr...

Preeclampsia (PE) is a pregnancy-related syndrome affecting about 3-8% of pregnancies, causing high maternal and fetal mortality1. Our group has reported a significant increase in free fetal hemoglobin (HbF) in the placenta and maternal blood in PE2-5. The placenta is an extracellular hematopoietic organ during development. At a certain stage in em...

After bone marrow stromal cells (BMSCs also known as mesenchymal stem cells of bone marrow origin) were used successfully to treat graft versus host disease in a single human subject, [1] many investigators studied the immune-suppressive properties of BMSCs and later adipose tissue derived MSCs (AMSC). The field has expanded significantly and there...

Patients with systemic mastocytosis (SM) have a wide variety of problems, including skeletal abnormalities. The disease results from a mutation of the stem cell receptor (c-kit) in mast cells and we wondered if the function of bone marrow stromal cells (BMSCs; also known as MSCs or mesenchymal stem cells) might be affected by the invasion of bone m...

For nearly two centuries, developmental biologists have known that body organs are derived from distinct germ layers. They have argued that adult stem cells formed in one of these, mesoderm for example, cannot give rise to cells that originate in another. We disagree. An exception to this "rule" has been described in crayfish recently. In this spec...

Serotonin and oxytocin influence aggressive and anxiety-like behaviors, though it is unclear how the two may interact. That the oxytocin receptor is expressed in the serotonergic raphe nuclei suggests a mechanism by which the two neurotransmitters may cooperatively influence behavior. We hypothesized that oxytocin acts on raphe neurons to influence...

Bone marrow stromal cells (BMSCs, also known as mesenchymal stem cells or MSCs) represent a unique cell population in the bone marrow with a long-known function to support hematopoiesis and replace skeletal tissues. The recent discovery that BMSCs also possess potent immunoregulatory features attracted a great deal of attention from stem cell biolo...

Human ciliopathies are genetic disorders caused by mutations in genes responsible for the formation and function of primary cilia. Some are associated with hyperphagia and obesity (e.g., Bardet-Biedl Syndrome, Alström Syndrome), but the mechanisms underlying these problems are not fully understood. The human gene ANKRD26 is located on 10p12, a locu...

Bone marrow stromal cells (BMSCs, frequently also called MSCs) represent a cell population within the bone marrow, a subset of which contains multipotent stem cells. Their primary role is to produce and maintain both bone tissue and bone marrow microenvironment necessary for hematopoiesis. The latter is achieved by secreting a wide variety of diffe...

The immunoregulatory functions of bone marrow-derived stromal cells (BMSCs), also called mesenchymal stromal/stem cells (MSCs), have been studied extensively in recent years. Although there is still some confusion in the literature about the nomenclature, for the sake of simplicity, we will use the abbreviation MSC below, referring to cells isolate...

There are several clinical trials worldwide using bone marrow stromal cells (BMSCs) as a cellular therapy to modulate immune responses in patients suffering from various inflammatory conditions. A deeper understanding of the molecular mechanisms involved in this modulatory effect could help us design better, more effective protocols to treat immune...

Since the replacement of the hematopoietic system became feasible through bone marrow (BM) transplantation, the idea of how to replace other organs of the body has been in the forefront of medical research. Scientists have been searching for the ideal stem cell that could be manipulated to differentiate into any tissue. Although the embryonal stem...

Mast cells (MCs) have a central role in the induction of allergic inflammation, such as seen in asthma, and contribute to the severity of certain autoimmune diseases, such as rheumatoid arthritis. The MC thus represents an important inflammatory cell, and one which has resisted therapeutic attempts to alter its role in disease. Because bone marrow-...

We studied the effect of permanent unilateral middle cerebral artery occlusion (PMCAO) on the generation of bone marrow (BM)-derived astrocytes in female mice previously transplanted with enhanced green fluorescent protein-expressing BM from male donors. In addition to an untreated PMCAO group, one group of mice also received intracerebral infusion...

Skin samples taken from 6 female patients receiving allogeneic bone marrow transplants (BMT) from male siblings (n=5) or from unrelated human leukocyte antigen (HLA)-matched male donor (n=1) due to hematological malignancies were studied for the presence of donor cells. One nontransplanted male and 1 female control that received female BM were used...

Cell biologists have long realized that most cells do not live as long as the organisms they comprise; thus, cells in almost every tissue need to be renewed/replaced during the natural lifespan of the organism. Depending on the turnover rate of cells in any given organ, this process can be very frequent or very rare. Epithelial cells in the mouth a...

This chapter describes neural and non-neural stem cells as novel therapeutic modalities for brain injury. The embryonic brain develops as part of the ectoderm from the primitive neural tube. Cells lining the neural tube form the primitive ventricular zone. These primitive cells are neuroepithelial cells that are the most primitive endogenous neural...

Non-obese diabetic (NOD) mice develop Sjögren's-like syndrome (Ss) and a gradual loss of saliva secretory function. Our previous study showed that injections of matched normal spleen cells with Complete Freund's Adjuvant (CFA) reversed salivary gland dysfunction in 14-week-old NOD mice, which had established Ss. The spleen and bone marrow are close...

Treatment for most patients with head and neck cancers includes ionizing radiation. A consequence of this treatment is irreversible damage to salivary glands (SGs), which is accompanied by a loss of fluid-secreting acinar-cells and a considerable decrease of saliva output. While there are currently no adequate conventional treatments for this condi...

Blood- and marrow-derived stem cells (BMDSCs) provide disease-ameliorating effects for cardiovascular and autoimmune diseases. Microchimerism from donor BMDSCs has been reported in several recipient tissues. We hypothesized that this finding suggests a potential use of BMDSCs in the treatment of salivary dysfunctions. We investigated the presence o...

Bone marrow stromal cells [BMSCs; also known as mesenchymal stem cells (MSCs)] effectively suppress inflammatory responses in acute graft-versus-host disease in humans and in a number of disease models in mice. Many of the studies concluded that BMSC-driven immunomodulation is mediated by the suppression of proinflammatory Th1 responses while rebal...

Bone marrow-derived stromal cells (BMSCs, or as they are frequently referred to as mesenchymal stem cells) have been long known to support hematopoiesis and to regenerate bone, cartilage, and adipose tissue. In the last decade, however, a vast amount of data surfaced in the literature to suggest new roles for these cells including tissue regenerati...

The salivary glands often are severely and permanently damaged by therapeutic irradiation for cancer of the head and neck. The markedly reduced quantity and quality of saliva results in greatly increased susceptibility to dental caries and infection of the oral mucosa and alveolar bone. Recently, subcapsular injection of cultured mouse salivary gla...

Oral Diseases (2010) 16, 129–135 Adult and embryonic stem cells have drawn a lot of attention in the last decade as new tools in regenerative medicine. A variety of such cells have been discovered and put forward as candidates for use in cell replacement therapy. Investigators hope that some, if not all, of our organs can be replaced or restored to...

The cytokine transforming growth factor alpha (TGF alpha) has proangiogenic and proneurogenic effects and can potentially reduce infarct volumes. Therefore, we administered TGF alpha or vehicle directly into the area surrounding the infarct in female mice that received gender-mismatched bone marrow transplants from green fluorescent protein (GFP)-e...

Nature Medicine is the premier journal for biomedical research. Respected internationally for the quality of its papers on areas ranging from infectious disease to cancer and neurodegeneration, Nature Medicine aims to bridge the gap between basic research and medical advances and is consistently ranked the number one journal by the Institute of Sci...

Extensive research has been conducted on the various appetite peptides produced in different areas throughout the human body and their effects on the satiety/feeding centers in the CNS. Many of these molecules have been looked at and isolated in the stomach and GI system, but not in human salivary glands. Objective: Since salivary glands play suc...

The molecular pathways that promote the proliferation and maintenance of pituitary somatotrophs and other cell types of the anterior pituitary gland are not well understood at present. However, such knowledge is likely to lead to the development of novel drugs useful for the treatment of various human growth disorders. Although muscarinic cholinerg...

Sepsis causes over 200,000 deaths yearly in the US; better treatments are urgently needed. Administering bone marrow stromal cells (BMSCs -- also known as mesenchymal stem cells) to mice before or shortly after inducing sepsis by cecal ligation and puncture reduced mortality and improved organ function. The beneficial effect of BMSCs was eliminated...

To create a library enriched in cDNAs from preeclamptic placentas to print onto microarrays for placental profiling of preeclampsia (PE) and high risk pregnancies. Prospective study. University women's clinic and academic research laboratory. Ten patients with PE, 5 with PE and bilateral notching, 5 with bilateral notching without PE, and 15 normot...

Granulocyte colony-stimulating factor (G-CSF) induces proliferation of bone marrow-derived cells. G-CSF is neuroprotective after experimental brain injury, but the mechanisms involved remain unclear. Stem cell factor (SCF) is a cytokine important for the survival and differentiation of hematopoietic stem cells. Its receptor (c-kit or CD117) is pres...

Tuberoinfundibular peptide of 39 residues (TIP39) was identified as a PTH 2 receptor ligand. We report that mice with deletion of Tifp39, the gene encoding TIP39, are sterile. Testes contained Leydig and Sertoli cells and spermatogonia but no spermatids. Labeling chromosome spreads with antibodies to proteins involved in recombination showed that s...

Considerable attention has focused on regulation of central tryptophan hydroxylase (TPH) activity and protein expression. At the time of these earlier studies, it was thought that there was a single central TPH isoform. However, with the recent identification of TPH2, it becomes important to distinguish between regulatory effects on the protein exp...

In this study, we investigated the effect of chronic repeated restraint (RR) on prolactin-releasing peptide (PrRP) expression. In the brainstem, where PrRP colocalize with norepinephrine in neurons of the A1 and A2 catecholaminergic cell groups, the expression of tyrosine hydroxylase (TH) has also been examined. In the brainstem, but not in the hyp...

Obesity is a major health hazard that is caused by a combination of genetic and behavioral factors. Several models of obesity have been described in mice that have defects in the production of peptide hormones, in the function of cell membrane receptors, or in a transcription factor required for neuronal cell development. We have been investigating...

Investigation of hyperalgesia at the spinal transcriptome level indicated that carrageenan-induced inflammation of rat hind paws leads to a rapid but sustained increase in S100A8 and S100A9 expression, two genes implicated in the pathology of numerous inflammatory diseases including rheumatoid arthritis and gout. In situ hybridization revealed that...

The uterine endometrium is composed of epithelial and stromal cells, which undergo extensive degeneration and regeneration in every estrous cycle, and dramatic changes occur during pregnancy. The high turnover of cells requires a correspondingly high level of cell division by progenitor cells in the uterus, but the character and source of these cel...

The effect of chronic ethanol feeding on hepatic mitochondrial morphology and histochemically measured succinic dehydrogenase activity was assessed. Five monkeys of the species Macaca radiata received a nutritionally adequate diet containing 50% of the calories as ethanol, while five others were pair-fed the same diet except that ethanol was isocal...

The effect of chronic ethanol feeding was determined on parameters of hepatic collagen metabolism in the monkey. Four monkeys of the species Macaca radiata received a nutritionally adequate diet containing 50% of the calories as ethanol, while four others were pair-fed a diet in which ethanol was isocalorically substituted by carbohydrate. Liver bi...

After immunohistochemistry (IHC) began to be used routinely, a number of investigators worked on methods for staining multiple molecules in the same tissue sections or cells. Achieving this goal was not easy, however. One reason for this is that the majority of primary antibodies used in IHC reactions are raised in rabbits, and recognizing signals...

Non-obese diabetic (NOD) mice exhibit autoimmune diabetes and Sjögren's-like syndrome. To test whether a treatment that reverses end-stage diabetes in the NOD mouse would affect their Sjögren's-like syndrome. NOD mice have a proteasome defect. Improperly selected naive T cells escape, but can be killed by reintroducing major histocompatibility comp...

The green fluorescent protein (GFP) is among the most commonly used expression markers in biology. GFP-tagged cells have played a particularly important role in studies of cell lineage. Sensitive detection of GFP is crucially important for such studies to be successful, and problems with detection may account for discrepancies in the literature reg...

Bone marrow derived stem cells (BMDSCs) have been reported to form neurons and supportive cells in the brain. We describe a technique that combines the simplicity of in vitro studies with many of the advantages of in vivo experiments. We cultured mouse brain slices, deposited GFP-tagged BMDSCs evenly distributed on their surfaces, and then added te...

In spite of the commonly held belief that 'the brain does not regenerate', it is now accepted that postnatal neurogenesis does occur. Thus, one wonders whether cellular-replacement therapy might be used to heal the brain in diseases caused by neuronal cell loss. The existence of neural stem cells has been demonstrated by many scientists and is now...

There are two major well-characterized populations of post-natal (adult) stem cells in bone marrow: hematopoietic stem cells which give rise to blood cells of all lineages, and mesenchymal stem cells which give rise to osteoblasts, adipocytes, and fibroblasts. For the past 50 years, strict rules were taught governing developmental biology. However,...

G protein-coupled receptors (GPCRs) mediate effects of extracellular signaling molecules in all the body's cells. These receptors are encoded by scarce mRNAs; therefore, detecting their transcripts with conventional microarrays is difficult. We present a method based on multiplex PCR and array detection of amplicons to assay GPCR gene expression wi...

Chong et al., Nishio et al., and Suri et al. (Reports, 24 March 2006, pp. 1774, 1775, and 1778) confirmed that treating nonobese diabetic (NOD) mice with an immune adjuvant and semisyngenic spleen cells can reverse the disease but found that spleen cells did not contribute to the observed recovery of pancreatic islets. We show that islet regenerati...

Characteristics of the increasing effect for the concentration of intracellular calcium ions ([Ca2+]i) by high-KCl application were investigated in the neuroblastoma×glioma hybrid NG108-15 cell line (NG108-15 cells). The present study confirmed that the increasing effect of [Ca2+]i by high-KCl application in single NG108-15 cells, differentiated wi...

Failure to detect co-expression of estrogen receptor-alpha (ERalpha) and proliferation 'markers' such as Ki67 in human mammary epithelium led to the view that estrogen acts indirectly to stimulate mammary epithelial proliferation. The mitotic index was so low in prior studies, however, that transient co-expression of ERalpha and Ki67 during the cel...

Multiple studies have reported that adult cells of bone marrow origin can differentiate into muscle, skin, liver, lung, epithelial cells, and neurons. To determine whether such cells might produce neurons and other cells in the human brain, we examined paraffin sections from female patients who had received bone marrow transplants from male donors....

Almost 10 yr have passed since we first entertained the idea that circulating blood cells originating in the bone marrow might contribute to central nervous system (CNS) cell lineages. Initially, we showed that microgalia are derived from bone marrow stem cells (BMSCs). Later, we found that BMSCs might also give rise to other neural cells--even neu...

Expression of genes is manifested by the production of RNA transcripts within cells. Hybridization histochemistry (or in situ hybridization) permits localization of these transcripts with cellular resolution or better. Furthermore, the relative amounts of transcripts detected in different tissues or in the same tissues in different states (e.g., ph...

Several lines of evidence support the concept that pluripotent stem cells reside in the hematopoietic system of adults, but each has been questioned for valid reasons. Thus, the results reported to date after infusion of bone marrow stem cells, may be due to cell fusion, non-physiological de-differentiation and subsequent differentiation to lineage...

Mammalian organs are typically comprised of several cell populations. Some (e.g. brain) are very heterogeneous, and this cellular complexity makes it difficult, if not impossible, to interpret expression profiles obtained with microarrays. Instruments, such as those manufactured by Leica or Arcturus, that permit laser capture microdissection of spe...

A major projection of the medial striatum (lobus parolfactorius, LPO) of birds is the striato-ventrotegmental pathway projecting to the area ventralis tegmentalis. In the present study, we investigated the morphology and connectivity of striato-ventrotegmental neurons in the medial LPO. The neurons were identified by injecting the fluorescent retro...

Familial dysautonomia (FD) is the best-known and most common member of a group of congenital sensory/autonomic neuropathies characterized by widespread sensory and variable autonomic dysfunction. As opposed to the sensory/motor neuropathies, little is known about the causes of neuronal dysfunction and loss in the sensory/autonomic neuropathies. FD...

Small iontophoretic injections of the anterograde tracer Phaseolus vulgaris leucoagglutinin were placed in the thalamic anterior dorsomedial nucleus (DMA) of domestic chicks. The projections of the DMA covered the rostrobasal forebrain, ventral paleostriatum, nucleus accumbens, septal nuclei, Wulst, hyperstriatum ventrale, neostriatal areas, archis...

Adult bone marrow-derived (BMD) cells could be used to repair damaged organs and tissues, but the intrinsic plasticity of these cells has been questioned by results of in-vitro studies suggesting that such cells might fuse with other cells giving the appearance of differentiation. We aimed to determine whether fusion events are important in vivo. T...

Neural crest stem cells (NCSC) give rise to the adrenal medullary chromaffin cells, the dorsal root ganglia, autonomic ganglia, cranial nerve ganglia, enteric ganglia, Schwann cells, satellite cells, and some non-neural tissue. Prior to the onset of migration of NCSCs single dorsal neural tube cells can give rise to both CNS neural stem cells and n...

Castro et al . ([1][1]) reported that bone marrow cells (BMCs) fail to generate neural cells in vivo. The bone marrow they injected came from mice in which LacZ expression was driven by a widely expressed trapped promoter. In principle, such cells and their progeny should readily be detected by