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1.
Water Res ; 233: 119802, 2023 Apr 15.
Article in English | MEDLINE | ID: mdl-36871379

ABSTRACT

20 years since the first report on the biofouling potential of chemicals used for scale control, still, antiscalants with high bacterial growth potential are used in practice. Evaluating the bacterial growth potential of commercially available antiscalants is therefore essential for a rational selection of these chemicals. Previous antiscalant growth potential tests were conducted in drinking water or seawater inoculated with model bacterial species which do not represent natural bacterial communities. To reflect better on the conditions of desalination systems, we investigated the bacterial growth potential of eight different antiscalants in natural seawater and an autochthonous bacterial population as inoculum. The antiscalants differed strongly in their bacterial growth potential varying from ≤ 1 to 6 µg easily biodegradable C equivalents/mg antiscalant. The six phosphonate-based antiscalants investigated showed a broad range of growth potential, which depended on their chemical composition, whilst the biopolymer and the synthetic carboxylated polymers-based antiscalants showed limited or no significant bacterial growth. Moreover, nuclear magnetic resonance (NMR) scans enabled antiscalant fingerprinting, identifying components and contaminants, providing a rapid and sensitive characterization, and opening opportunities for rational selection of antiscalants for biofouling control.


Subject(s)
Biofouling , Water Purification , Seawater/chemistry , Osmosis , Membranes, Artificial
2.
Membranes (Basel) ; 12(8)2022 Aug 18.
Article in English | MEDLINE | ID: mdl-36005707

ABSTRACT

The shortage of fresh water resources has made the desalination of seawater a widely adopted technology. Seawater reverse osmosis (SWRO) is the most commonly used method for desalination. The SWRO process is energy-intensive, and most of the energy in SWRO is spent on pressurizing the seawater to overcome the osmotic barrier for producing fresh water. The pressure needed depends on the salinity of the seawater, its temperature, and the membrane surface properties. Membrane compaction occurs in SWRO due to hydraulic pressure application for long-term operations and operating temperature fluctuations due to seasonal seawater changes. This study investigates the effects of short-term feed water temperature increase on the SWRO process in a full-scale pilot with pretreatment and a SWRO installation consisting of a pressure vessel which contains seven industrial-scale 8" diameter spiral wound membrane elements. A SWRO feed water temperature of 40 °C, even for a short period of 7 days, caused a permanent performance decline illustrated by a strong specific energy consumption increase of 7.5%. This study highlights the need for membrane manufacturer data that account for the water temperature effect on membrane performance over a broad temperature range. There is a need to develop new membranes that are more tolerant to temperature fluctuations.

3.
Case Rep Gastrointest Med ; 2019: 4684631, 2019.
Article in English | MEDLINE | ID: mdl-31737380

ABSTRACT

Two patients are described with large stones in the common bile duct. Standard ERCP was not possible. Both patients were successfully treated with percutaneous access and use of the ureteroscope with the holmium laser.

4.
Blood Cancer J ; 7(9): e605, 2017 09 08.
Article in English | MEDLINE | ID: mdl-28885611

ABSTRACT

The effect of prior malignancy on the risk of developing, and prognosis of, acute lymphoblastic leukemia (ALL) is unknown. This observational study utilized the California Cancer Registry to estimate the risk of developing ALL after a prior malignancy using standardized incidence ratios (SIRs, 95% confidence intervals). ALL occurring after a malignancy with an SIR>1 (increased-risk (IR) malignancies) was considered secondary ALL (s-ALL). Adjusted hazard ratios (aHRs, 95% confidence intervals) compared the effect of s-ALL with de novo ALL on overall survival. A total of 14 481 patients with ALL were identified (1988-2012) and 382 (3%) had a known prior malignancy. Any prior malignancy predisposed patients to developing ALL: SIR 1.62 (1.45-1.79). Hematologic malignancies (SIR 5.57, 4.38-6.98) and IR-solid tumors (SIR 2.11, 1.73-2.54) increased the risk of developing ALL. s-ALL increased the risk of death compared with de novo ALL (aHR 1.38 (1.16-1.63)) and this effect was more pronounced among younger patients (age<40 years: aHR 4.80 (3.15-7.30); age⩾40 years: aHR 1.40 (1.16-1.69)) (interaction P<0.001). This population-based study demonstrates that s-ALL is a distinct entity that occurs after specific malignancies and carries a poor prognosis compared with de novo ALL, particularly among patients <40 years of age.


Subject(s)
Neoplasms, Second Primary/mortality , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Registries , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , California/epidemiology , Child , Child, Preschool , Disease-Free Survival , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Neoplasms, Second Primary/diagnosis , Neoplasms, Second Primary/therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Risk Factors , Survival Rate
5.
Clin Exp Dermatol ; 41(3): 294-6, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26508289

ABSTRACT

Laugier-Hunziker syndrome (LHS) is a rare acquired disorder characterized by macu-lar pigmentation of the lips and oral mucosa, with frequent longitudinal melanonychia. Involvement of other areas, such as the genitalia and fingers, has rarely been described. LHS is a benign condition with no known systemic manifestations. We report the case of a woman who developed melanotic macules on her fingers and elbow 16 years after the onset of pigmentation of her lips. This unusual feature of LHS in our patient was associated with irritant contact dermatitis and viral warts. Only two cases of an association with an inflammatory dermatosis have been reported previously in the literature.


Subject(s)
Dermatitis, Contact/pathology , Hyperpigmentation/pathology , Warts/pathology , Elbow , Female , Fingers , Hand Dermatoses/pathology , Humans , Irritants/adverse effects , Lip Diseases/pathology , Middle Aged , Syndrome , Tongue Diseases/pathology
6.
Clin Exp Dermatol ; 41(1): 53-6, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26175017

ABSTRACT

Scleromyxoedema is a rare disease characterized by a generalized papular and sclerodermoid cutaneous eruption. It is associated with fibroblast proliferation and mucin deposition in the dermis. Most patients have a monoclonal gammopathy, defined by the presence of IgG. Treatment of scleromyxoedema is challenging, but there is mounting evidence to support the use of intravenous immunoglobulin (IVIg). Individual reports of systemic complications have been described. Dermatoneuro syndrome (DNS) is a rare but sometimes fatal manifestation, which consists of a triad of fever, coma and seizures preceded by a flu-like illness. We describe a patient with scleromyxoedema who developed DNS. Our case highlights interesting findings suggesting that DNS may have a viral aetiology. In addition, this case demonstrates a favourable response of the cutaneous features of scleromyxoedema to IVIg.


Subject(s)
Influenza, Human/complications , Scleromyxedema/complications , Seizures/virology , Humans , Influenza A virus/isolation & purification , Male , Middle Aged , Paraproteinemias/etiology , Syndrome
8.
Ann Fr Anesth Reanim ; 32(7-8): 516-9, 2013.
Article in English | MEDLINE | ID: mdl-23916514

ABSTRACT

Major trauma remains a worldwide cause of morbi-mortality. Early mortality is the consequence of hemorrhagic shock and traumatic brain injury. During early resuscitation, anaesthesia is often mandatory to perform surgery. It is mandatory to master the hemodynamic effects of hypnotic drugs in order to anticipate their potential deleterious effects in the setting of hemorrhagic shock. After early resuscitation, trauma patients present a high prevalence of nosocomial pneumonia, which sustains major morbidity. Nosocomial pneumonia are the consequence of an overwhelming systemic inflammatory response syndrome (SIRS) as well as a trauma-related immunosuppression. The administration of hemisuccinate of hydrocortisone modulates the SIRS and reduces the risk of nosocomial pneumonia as well as the length of mechanical ventilation. Finally in the operating theatre, fighting against hypothermia and un-anatomical positions, which can aggravate rhabdomyolysis, are both mandatory.


Subject(s)
Anesthesia , Immunity/physiology , Resuscitation , Surgical Procedures, Operative/methods , Wounds and Injuries/immunology , Wounds and Injuries/surgery , Anesthetics, Intravenous , Etomidate , Excitatory Amino Acid Antagonists/therapeutic use , Humans , Hypothermia/etiology , Hypothermia/therapy , Ketamine/therapeutic use , Neuromuscular Nondepolarizing Agents/therapeutic use , Pituitary-Adrenal System/immunology , Pituitary-Adrenal System/physiology , Pituitary-Adrenal System/physiopathology , Propofol , Rhabdomyolysis/etiology , Rhabdomyolysis/therapy , Shock, Hemorrhagic/drug therapy , Shock, Hemorrhagic/therapy
9.
J Perinatol ; 33(10): 754-8, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23702620

ABSTRACT

OBJECTIVE: To determine if serum screen analytes identify preeclamptic patients at risk for small-for-gestational age newborns, maternal laboratory abnormalities and preterm delivery (<37 weeks gestation). STUDY DESIGN: Using a retrospective cohort of 102 preeclamptic patients, associations between serum screen analytes and newborn birth-weight percentile, gestational age (GA) at delivery and maternal pre-delivery laboratory abnormalities were evaluated using correlation coefficients and local polynomial regression. RESULT: Inhibin-A and maternal serum alpha fetoprotein were inversely correlated with newborn birth-weight percentile (-0.27, P=0.006; -0.35, P=0.00004) and delivery GA (r=-0.42, P<0.0001; r=-0.26, P=0.008) and positively correlated with pre-delivery aspartate aminotransferase (r=0.22, P=0.03; r=0.21, P=0.04) and lactate dehydrogenase (r=0.33, P=0.0007; r=0.29, P=0.004). A positive correlation was noted between both second-trimester beta human chorionic gonadotropin and estriol and maternal pre-delivery creatinine (0.28, P=0.004; 0.4, P<0.0001, respectively). Hundred percent of patients with ≥ 2 abnormal analytes delivered before 37 weeks gestation. CONCLUSION: Preeclamptic patients with abnormal serum screen analytes are more likely to have small-for-gestational age newborns, deliver preterm and have pre-delivery laboratory abnormalities.


Subject(s)
Maternal Serum Screening Tests , Pre-Eclampsia/blood , Pregnancy Proteins/blood , Adult , Birth Weight , Chorionic Gonadotropin, beta Subunit, Human/blood , Estriol/blood , Female , Gestational Age , HELLP Syndrome/blood , Humans , Infant, Newborn , Infant, Small for Gestational Age/blood , Inhibins/blood , Pre-Eclampsia/classification , Pre-Eclampsia/diagnosis , Pregnancy , Pregnancy Trimester, Second , Pregnancy-Associated Plasma Protein-A/analysis , Premature Birth/blood , Retrospective Studies , alpha-Fetoproteins/analysis
10.
J Acoust Soc Am ; 132(5): 3559-68, 2012 Nov.
Article in English | MEDLINE | ID: mdl-23145635

ABSTRACT

Mulloway (Argyrosomus japonicus) in Mosman Bay, Western Australia produce three call categories associated with spawning behavior. The determination of call source levels and their contribution to overall recorded sound pressure levels is a significant step towards estimating numbers of calling fish within the detection range of a hydrophone. The source levels and ambient noise also provide significant information on the impacts anthropogenic activity may have on the detection of A. japonicus calls. An array of four hydrophones was deployed to record and locate individual fish from call arrival-time differences. Successive A. japonicus calls produced samples at various ranges between 1 and 100 m from one of the array hydrophones. The three-dimensional localization of calls, together with removal of ambient noise, allowed the determination of source levels for each call category using observed trends in propagation losses and interference. Mean source levels (at 1 m from the hydrophone) of the three call categories were calculated as 163 ± 16 dB re 1 µPa for Category 1 calls (short call of 2-5 pulses); 172 ± 4 dB re 1 µPa for Category 2 calls (long calls of 11-32 pulses); and 157 ± 5 dB re 1 µPa for Category 3 calls (series of successive calls of 1-4 pulses, increasing in call rate).


Subject(s)
Fishes/physiology , Vocalization, Animal , Acoustics/instrumentation , Animals , Pressure , Reproduction , Signal Processing, Computer-Assisted , Sound Spectrography , Swimming , Time Factors , Transducers, Pressure
11.
J Perinatol ; 32(10): 757-62, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22193928

ABSTRACT

OBJECTIVE: Uric acid is known to be elevated in preeclampsia. We sought to determine if uric acid levels on admission correlate with the length of expectant management in preterm patients with preeclampsia. STUDY DESIGN: A retrospective chart review was conducted on singleton preeclamptic pregnancies delivered between 24 0/7 and 37 0/7 weeks' gestation at Tufts Medical Center between January 2005 and December 2007. Patients with a multiple gestation and those transferred or discharged before delivery were excluded. Data regarding signs and symptoms of preeclampsia, laboratory values, pregnancy complications and outcome were abstracted from the medical records. Correlation between admission uric acid level and days of expectant management was assessed. The relative risk (RR) was used to estimate the effect of uric acid levels on expectant management length >7 days. Mantel-Haenszel χ(2) values were used to construct 95% confidence intervals (CIs) around the RR. RESULT: Four hundred seventy-one charts were reviewed. Of these, 190 met inclusion criteria. In all, 55 patients (28.9%) were managed expectantly for >1 week. Admission uric acid level correlated with days of expectant management (P<0.0001). Uric acid levels at admission were categorized as ≤4.0 mg dl(-1) (low uric acid level), 4.1 to 6.0 mg dl(-1) (medium) and ≥6.1 mg dl(-1) (high). Relative to women with high uric acid levels at admission, we observed a sevenfold higher rate of extending expectant management for >1 week among women with low uric acid level (7.0; 95% CI: 3.34 to 14.68). Women with medium uric acid levels at admission also had a higher likelihood of prolonging pregnancy relative to women with high uric acid levels (RR: 2.81; 95% CI: 1.32 to 5.96) (P-value for trend <0.0001). CONCLUSION: Admission uric acid levels correlate with the length of expectant management in preterm patients with preeclampsia. Pregnancy prolongation for >1 week is significantly more likely in patients with low and medium uric acid levels at the time of admission. Uric acid levels may be helpful in assessing disease severity and counseling preeclamptic patients regarding likelihood of extended expectant management.


Subject(s)
Pre-Eclampsia/blood , Uric Acid/blood , Adolescent , Adult , Delivery, Obstetric , Female , Gestational Age , Humans , Patient Admission , Pre-Eclampsia/therapy , Pregnancy , Prognosis , Retrospective Studies , Survival Analysis , Young Adult
12.
Gynecol Obstet Fertil ; 38(9): 515-20, 2010 Sep.
Article in French | MEDLINE | ID: mdl-20724205

ABSTRACT

Assisted Reproductive Techniques (ART) separating oocytes in sibling oocytes treated either by conventional IVF or ICSI is called mid-IVF/ICSI. We sum up here 487 attempts of this kind from six French ART centers. The mid-IVF/ICSI technique was performed in 5.6% of cases. The fertilization rate by micro-injected oocytes was significantly higher (P<0.01) than oocytes inseminated conventionally, 72.6% versus 53.4%. A failure of fertilization was observed only in mid-IVF in 21.6% of cases, which prevented a complete fertilization failure when we decided to propose to the couples concerned the mid-IVF/ICSI technique. Conversely, in 75.2% of cases, fertilization was found for the two batches of oocytes. The overall pregnancy rate has improved since the use of the mid-IVF/ICSI technique (33.1% versus 28.9%, P=0.013) and the fertilization failures decreased (10.4% versus 14.3%, P=0. 019). The pregnancy rate in only mid-IVF/ICSI cases is very high at 39.8% but for a selected population. The indications for mid-IVF/ICSI remain to be clarified especially with regard to male and idiopathic indications.


Subject(s)
Fertilization in Vitro , Oocytes/physiology , Sperm Injections, Intracytoplasmic , Female , France , Humans , Male , Pregnancy , Pregnancy Rate
13.
Phys Chem Chem Phys ; 12(37): 11517-35, 2010 Oct 07.
Article in English | MEDLINE | ID: mdl-20676445

ABSTRACT

We have conducted (75)As and (69)Ga Nuclear Magnetic Resonance (NMR) experiments to investigate order/disorder in Al(x)Ga(1-x)As lift-off films with x∼ 0.297 and 0.489. We were able to identify all possible As(Al(n)Ga(4-n)) sites with n = 0-4 coordinations in (75)As NMR spectra using spin-echo experiments at 18.8 Tesla. This was achieved by employing high rf field strengths using a small solenoid coil and an NMR probe specifically designed for this purpose. Spectral deconvolution, using an evolutionary algorithm, complies with the absence of long-range order if a CuAu based order parameter is imposed. An unconstrained fit shows a deviation of the statistics imposed by this type of ordering. The occupational disorder in the Ga and Al positions is reflected in a distribution of the Electric Field Gradients (EFGs) experienced at the different arsenic sites. We established that this can be modelled by summing the effects of the first coordination sphere and a Czjzek type distribution resulting from the compositional variation in the Al/Ga sub-lattice in the higher coordination spheres. (69)Ga 3QMAS and nutation data exclude the presence of highly symmetric sites and also show a distribution in EFG. The experimentally obtained quadrupolar interactions are in good agreement with calculations based on Density Functional Theory (DFT). Using additivity of EFG tensors arising from distant charge perturbations, we could use DFT to model the EFG distributions of the n = 0-4 sites, reproducing the Czjzek and extended Czjzek distributions that were found experimentally. On the basis of these calculations we conclude that the (75)As quadrupolar interaction is sensitive to compositional modulations up to the 7th coordination shell in these systems.

14.
ChemMedChem ; 3(9): 1371-6, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18576452

ABSTRACT

Knowledge about the orientation of ligands or inhibitors bound to a protein is vital for the development of new drugs. It was recently shown that solvent accessibility epitopes for protein ligands can be mapped by transferring magnetization from water molecules to the ligand to derive the ligand orientation. This is based on the fact that NMR signals of ligands arising from magnetization transferred from solvent molecules via the protein have a different sign from those arising from direct magnetization transfer from bulk water. Herein we critically evaluate the applicability of solvent accessibility mapping to derive binding orientations for ligands of two dehydrogenases (AKR1C3 and HSD17beta1) with very different binding pockets, including complexes in which the ligand is buried more deeply inside the protein. We also evaluate the possibility of using co-solvents, such as DMSO, for magnetization transfer.


Subject(s)
3-Hydroxysteroid Dehydrogenases/antagonists & inhibitors , Dimethyl Sulfoxide/chemistry , Epitopes/chemistry , Estradiol Dehydrogenases/antagonists & inhibitors , Flavonoids/pharmacology , Hydroxyprostaglandin Dehydrogenases/antagonists & inhibitors , Indomethacin/pharmacology , 3-Hydroxysteroid Dehydrogenases/chemistry , Aldo-Keto Reductase Family 1 Member C3 , Binding Sites/drug effects , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Estradiol Dehydrogenases/chemistry , Flavonoids/chemistry , Humans , Hydroxyprostaglandin Dehydrogenases/chemistry , Indomethacin/chemistry , Ligands , Magnetic Resonance Spectroscopy/methods , Magnetic Resonance Spectroscopy/standards , Magnetics , Models, Molecular , Molecular Structure , Protein Binding , Reference Standards , Solvents/chemistry , Surface Properties , Water/chemistry
15.
J Musculoskelet Res ; 11(2): 81-87, 2008.
Article in English | MEDLINE | ID: mdl-20209046

ABSTRACT

The objective of this paper was to study in vitro transfection of tendon cells and adherence of transfected cells to different tendon surfaces. Achilles tendon fibroblasts from 2-month-old New Zealand white rabbits were cultured to confluence, after which the cells were transfected by an adenovirus carrying either the ß-galactosidase reporter gene or the green fluorescent protein (GFP) gene at multiplicities of infection (MOIs) of 50, 100, or 500. Two days later, the cells were transplanted onto the surfaces of rabbit Achilles, peroneus brevis, flexor profundus, and extensor longus tendons. The tendons were assessed by X-gal staining after 9 days, and by GFP fluorescence at 7, 14, and 21 days. Twenty percent to 50% of the treated cells stained for ß-galactosidase at an MOI of 500. The GFP-labeled cells showed nearly 100% fluorescence at an MOI of 50. No positive cells were visible in the control group. The ß-galactosidase and GFP-expressing cells remained viable for as long as 3 weeks. It is possible to introduce foreign genes into rabbit tendon cells, transplant the cells onto tendon surfaces, and maintain viability of the cell/tendon construct for several weeks.

18.
Rev Med Liege ; 57(7): 443-8, 2002 Jul.
Article in French | MEDLINE | ID: mdl-12233219

ABSTRACT

A 12-year old female, suffering from recurring episodes of icterus and abdominal pain, is hospitalized in emergency. She is not anemic but her hemogram reveals a high level of hyperdense red blood cells (32%; controls 0-2.5%) and an abnormal reticulocyte count (201 x 10(3)/microL; controls 29-84 x 10(3)/microL), indicating a 3.5 fold increase in RBC production. The same abnormalities are found in the patient's mother. The blood smear shows few spherocytes. RBC osmotic fragility is increased only after incubation. Hereditary spherocytosis is diagnosed following electrophoresis of membrane proteins which reveals a deficiency in band 3, a protein which links the lipid bilayer to the cytoskeleton. This case of hemolytic anemia-illustrates the physiopathologic and diagnostic significance of hyperdense RBC, which reflect the cell dehydration associated with the membrane disorder.


Subject(s)
Erythrocytes/pathology , Spherocytosis, Hereditary/diagnosis , Spherocytosis, Hereditary/physiopathology , Abdominal Pain/etiology , Child , Diagnosis, Differential , Female , Humans , Jaundice/etiology , Membrane Proteins/chemistry , Pedigree
19.
Haematologica ; 86(11): 1209-18, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11694408

ABSTRACT

BACKGROUND AND OBJECTIVES: It may be useful to reduce the exposure of transplant recipients to homologous blood. This may be achieved by procuring donor-derived red blood cell (RBC) units, collecting more peripheral blood progenitor cells (PBPC) with a combination of granulocyte colony-stimulating factor (G-CSF) + recombinant human erythropoietin (rHuEpo) and by administering rHuEpo post-transplantation. DESIGN AND METHODS: Eight ABO-compatible donors were treated with rHuEpo and intravenous iron to collect 12 RBC units for use in their recipients. PBPC were collected after mobilization with rHuEpo and G-CSF in the same donors. The recipients received G-CSF and rHuEpo post-transplantation. A control group of 10 donor/recipient pairs received G-CSF alone for PBPC mobilization and after the transplantation. RESULTS: Eighty-six out of 91 planned RBC units were collected in the donors without significant decrease in hematocrit because of a 4-fold increase in RBC production despite functional iron deficiency. After 2 leukaphereses, the cumulative yields of NC and CFU-GM were lower in the study group while those of BFU-E, CFU-Mix and CD34+ cells were similar. However, erythroid recovery was significantly accelerated in the study group. INTERPRETATION AND CONCLUSIONS: Collection of 12 RBC units within 6 weeks is feasible with rHuEpo and intravenous iron; this strategy allows a dramatic reduction in recipient exposure to homologous blood; rHuEpo has no synergistic effect with G-CSF for mobilization of PBPC in normal donors and may even be deleterious; and rHuEpo in the recipient may enhance erythroid engraftment.


Subject(s)
Cytapheresis/methods , Erythropoietin/administration & dosage , Granulocyte Colony-Stimulating Factor/administration & dosage , Hematopoietic Stem Cell Mobilization/methods , Adolescent , Adult , Blood Donors , Erythrocyte Transfusion , Feasibility Studies , Female , Graft Survival , Hematopoietic Stem Cell Transplantation , Humans , Leukapheresis , Male , Middle Aged , Prospective Studies , Recombinant Proteins , Transplantation, Homologous
20.
Exp Hematol ; 29(11): 1256-69, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11698121

ABSTRACT

OBJECTIVE: We previously showed that the distributions of the numbers of doublings (NbD) undergone by individual megakaryocyte progenitors before commitment to polyploidization are markedly skewed and can consistently be fitted to straight lines when plotted on semilogarithmic coordinates. The slope of such lines, which yields the probability of polyploidization per doubling, is made less steep by stimulators of megakaryocyte colony formation and is less steep in mixed erythroid-megakaryocyte than in pure megakaryocyte colonies. Therefore, megakaryocytopoiesis provides a unique model for the study of clonal heterogeneity in a hemopoietic lineage, which is the subject of this review. DATA SOURCES: Articles relevant to the interpretation of these data were selected from the authors' and public databases. DATA SYNTHESIS: Exponential NbD distributions were first explained by postulating that following the assembly of thrombopoiesis-specific regulators, megakaryocyte progenitors require only a single random event to arrest proliferation and commit to polyploidization. However, this stochastic model was refuted by data indicating that intrinsic properties of individual progenitors affect the NbD they achieve. We suggest that the unequal repartition of critical compounds (including receptors, signaling molecules, and gene regulators) inherent in the stem cell-progenitor transition causes a heritable heterogeneity in megakaryocyte progenitor responsiveness to polyploidization inducers. This model would be compatible with 1) the evidence for intraclonal synchronization in megakaryocyte and other hemopoietic clones generated by committed progenitors; 2) the low probability of polyploidization of the relatively insensitive bipotent megakaryocyte progenitors; and 3) the thesis that stimulators act in part by recruiting megakaryocyte progenitor cells endowed with lesser responsiveness to polyploidization inducers and higher proliferative potential. CONCLUSION: The responsiveness of individual megakaryocyte progenitors to polyploidization inducers may be a major determinant of the exponential shape of NbD distributions.


Subject(s)
Hematopoiesis , Hematopoietic Stem Cells/cytology , Megakaryocytes/cytology , Animals , Cell Cycle/drug effects , Cell Division/drug effects , Cellular Senescence , Clone Cells/cytology , Clone Cells/drug effects , Erythroid Precursor Cells/cytology , Erythroid Precursor Cells/drug effects , Genetic Variation , Hematopoiesis/drug effects , Hematopoietic Stem Cells/drug effects , Humans , Megakaryocytes/drug effects , Mice , Mitogens/pharmacology , Polyploidy , Rats , Stochastic Processes
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