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M C Yoder

Publications and source records attributed to M C Yoder.

At least 55 records · Page 3Linked to original sources

Matrix molecule interactions with hematopoietic stem cells.

We have reviewed some aspects of the production, distribution, and organization of fibronectin in the bone marrow ECM and discussed HSC-fibronectin interactions. Many questions remain. Which isoforms of fibronectin are produced in the bone marrow during ontogeny, normal hematopoiesis, and pathophysiologic challenges to the marrow microenvironment? Do HSCs interact with ED-A- and ED-B-containing fibronectin isoforms the same way they interact with plasma fibronectin? Are different fibronectin isoforms selectively expressed in different regions of the bone marrow, in keeping with the spatial organization of HSC and hematopoietic progenitor cell compartments? Addressing these questions may give us a better understanding of the role of fibronectin in HSC localization, proliferation, and differentiation. Considerable information regarding the synthesis and secretion of other ECM molecules by adherent stromal cells has been derived from in vitro analysis of LTBMCs [3]. As with fibronectin, much remains to be learned of the precise distribution and composition of bone marrow ECM molecules during in vivo development; how in vivo bone marrow ECM secretion, turnover, and remodeling are regulated during normal and pathologic hematopoietic states; and the nature and importance of in vivo cellular interactions that occur between PHSC and individual constituents of the bone marrow ECM.

Animals↗

Murine yolk sac endoderm- and mesoderm-derived cell lines support in vitro growth and differentiation of hematopoietic cells.

The mechanisms involved in the induction of yolk sac mesoderm into blood islands and the role of visceral endoderm and mesoderm cells in regulating the restricted differentiation and proliferation of hematopoietic cells in the yolk sac remain largely unexplored. To better define the role of murine yolk sac microenvironment cells in supporting hematopoiesis, we established cell lines from day-9.5 gestation murine yolk sac visceral endoderm and mesoderm layers using a recombinant retrovirus vector containing Simian virus 40 large T-antigen cDNA. Obtained immortalized cell lines expressed morphologic and biosynthetic features characteristic of endoderm and mesoderm cells from freshly isolated yolk sacs. Similar to the differentiation of blood island hematopoietic cells in situ, differentiation of hematopoietic progenitor cells in vitro into neutrophils was restricted and macrophage production increased when bone marrow (BM) progenitor cells were cultured in direct contact with immortalized yolk sac cell lines as compared with culture on adult BM stromal cell lines. Yolk sac-derived cell lines also significantly stimulated the proliferation of hematopoietic progenitor cells compared with the adult BM stromal cell lines. Thus, yolk sac endoderm- and mesoderm-derived cells, expressing many features of normal yolk sac cells, alter the growth and differentiation of hematopoietic progenitor cells. These cells will prove useful in examining the cellular interactions between yolk sac endoderm and mesoderm involved in early hematopoietic stem cell proliferation and differentiation.

Animals↗

High proliferative potential colony-forming cell heterogeneity identified using counterflow centrifugal elutriation.

Murine high proliferative potential colony-forming cells (HPP-CFC) are known to be heterogenous with respect to proliferative capacity and in vitro responsiveness to hematopoietic growth factors. We have separated HPP-CFC into several subpopulations using counterflow centrifugal elutriation. Although HPP-CFC were identified in all of the elutriated fractions of both C3H/HeJ and C57BI/6J bone marrow cells, the distribution of HPP-CFC as well as of colony-forming units-granulocyte-macrophage (CFU-GM) in each fraction differed between these two strains of inbred mice. Six subsets of HPP-CFC were resolved that differed in growth factor responsiveness. A low-density HPP-CFC subpopulation was isolated that was distinct from day-12 spleen colony-forming units (CFU-S12), CFU-GM, and bone marrow stromal cells. This unique subpopulation of HPP-CFC is rate (3% to 9% of total HPP-CFC), appears to be lymphocyte-like in morphology, and behaves the most primitive of the HPP-CFC subsets by requiring multiple hematopoietic growth factors for optimal in vitro cloning. Further characterization of this subpopulation of HPP-CFC will determine the position of these cells in the HPP-CFC heirarchy.

Animals↗

In vitro comparison of multinucleated giant cell formation from human umbilical cord and adult peripheral blood mononuclear phagocytes.

The fetus and newborn infant are highly susceptible to infection by pathogens that are capable of intracellular survival. The invasion of these microbes usually stimulates a granulomatous host defense response in the fetus or neonate. Multinucleated giant cells (MGC) are the predominant cells composing the granuloma and represent the terminally differentiated state of activated macrophages. Because macrophages derived from human umbilical cord blood monocytes demonstrate some deficiencies in activated functions, we tested the ability of these cells to form MGC in vitro. Mononuclear cells from umbilical cord blood and adult peripheral blood were isolated and cultured for 7, 14, or 21 d before stimulation with phorbol myristate acetate (PMA), an agent known to stimulate MGC from mononuclear phagocytes in vitro. Spontaneous MGC formation occurred in both cord and adult blood mononuclear cell cultures by d 7 of incubation, although significantly fewer MGC formed in the cord blood cultures. PMA treatment of adult blood mononuclear cells resulted in a significant increase in MGC formation after 7, 14, or 21 d of culture, but PMA did not significantly increase MGC formation in cord blood cultures until 14 or 21 d of culture. Pretreatment of cord and adult blood mononuclear cells with 1,25-dihydroxyvitamin D3 inhibited PMA-induced MGC formation. However, when a purified population of cord blood, monocyte-derived macrophages were pretreated with 1,25-dihydroxyvitamin D3, PMA significantly increased MGC formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The use of bronchotomy and retrograde dilatation to repair acquired obliterative bronchial obstruction.

A case is presented of acquired obliterative mainstem bronchial obstruction with total ipsilateral lung atelectasis and contralateral lung hyperexpansion. The condition failed to improve after a suitable trial of positive airway pressure and medical management. Penetration of the obstructing lesion bia bronchotomy and a distal retrograde approach successfully opened the airway and the patient has been symptom-free for more than 9 months. This unique approach may be useful in other selected patients with similar acquired lesions.

Airway Obstruction↗

Pulmonary hypoplasia and persistent pulmonary hypertension: favorable clinical response to high-frequency jet ventilation.

Pulmonary hypoplasia in the neonate is frequently fatal. This article reports two neonates with a clinical diagnosis of pulmonary hypoplasia complicated by persistent pulmonary hypertension (PPHN). Though both infants were progressively worsening while receiving conventional mechanical ventilatory support, they survived when treated with high-frequency jet ventilation.

High-Frequency Jet Ventilation↗

Effect of dexamethasone on pulmonary inflammation and pulmonary function of ventilator-dependent infants with bronchopulmonary dysplasia.

Seventeen ventilator-dependent premature infants with bronchopulmonary dysplasia (BPD) were enrolled in a double-blind, placebo-controlled study to determine the effects of 3 days of intravenously administered dexamethasone (0.5 mg/kg/day) on pulmonary function, pulmonary inflammation, and the requirement for respiratory support (FIO2, ventilator peak pressure [PP], and respiratory rate [RR]). Assessment of pulmonary function included measurement of FVC, flow at 25% vital capacity (V25), and static compliance of the respiratory system (Crs), whereas pulmonary inflammation was assessed by the neutrophil count, ratio of elastase/2 x alpha-1-antitrypsin, and the concentrations of albumin and fibronectin in the tracheobronchial lavage (TBL) fluid. After 3 days of placebo treatment there were no significant changes in any of the measured parameters. In contrast, the dexamethasone-treated group demonstrated a significant decrease in respiratory support (FIO2: 50 versus 36%; PP: 21 versus 16 cm H2O; RR: 22 versus 14 breaths/min) and improved pulmonary function (Crs: 0.63 versus 0.85 ml/cm H2O/kg; V25: 23 versus 68 ml/s/kg). In addition, pulmonary inflammation was suppressed in the dexamethasone-treated group (neutrophils: 23 versus 11 x 10(4)/mg albumin: elastase/2 x alpha-1-antitrypsin: 0.24 versus 0.10; albumin: 7.1 versus 3.5 mg/dl; fibronectin: 33 versus 17 micrograms/mg albumin). We conclude that short-term treatment with dexamethasone improves pulmonary function and suppresses pulmonary inflammation as well as decreasing the respiratory support required by ventilator-dependent premature infants with BPD.

Albumins↗

Therapeutic administration of fibronectin: current uses and potential applications.

Fibronectins are a class of multifunctional glycoproteins that exist in soluble and insoluble forms. These glycoproteins are found in nearly all body fluids and in tissue extracellular matrices. Alterations in the normal synthesis, release, and distribution of fibronectins are characteristic features of certain human pathophysiologic conditions. The therapeutic administration of plasma fibronectin to human patients with defects in corneal wound healing and critically ill adult patients with multisystem organ failure appears clinically beneficial, although confirmation is needed from additional trials in progress. In vitro data suggest a role for fibronectin in enhancing (directly and indirectly) the function of phagocytes isolated from the blood of newborn infants. Although as yet untested, it is possible that fibronectin administration to the immunologically immature human neonate may improve host defenses and reduce the risk of nosocomial infection. Additional research is needed to define the factors that regulate the synthesis, isoform expression, and clearance of endogenous fibronectins during normal fetal and neonatal development. Continued research to define the role of endogenous fibronectins in augmenting the inflammatory response of the neonatal host is also required before rational immunotherapeutic interventions can be initiated.

Bacterial Infections↗

Rapid analysis of lymphocyte subsets in cord blood.

Several investigators have enumerated cellular populations in neonatal cord blood with variable results. In this study, the authors established reference ranges for lymphocyte subsets in cord blood from healthy newborns using a whole blood lysis technique on the Coulter Immunoprep Epics Leukocyte Preparation System (Coulter Immunology, Hialeah, FL). All analyses were performed on a flow cytometer by gating on forward angle versus 90 degrees light scatter. Lymphocytes demonstrated all surface markers examined, including T4, T8, T3, T11, B1, NKH-1, I3, and 4B4; 2H4 suppressor inducer lymphocytes were prominent in neonatal blood. The authors think this standardized system may be suitable for use in neonatal and pediatric patients because it quickly processes small aliquots of whole blood with minimal sample manipulation.

Fetal Blood↗

Pulmonary microcirculatory kinetics of neutrophils deficient in leukocyte adhesion-promoting glycoproteins.

The mechanism that causes neutrophils to sequester in the pulmonary circulation is unknown. Because the CD11/CD18 glycoprotein family on the surface membrane of neutrophils participates in many adhesive interactions with the endothelium, we investigated the role of these proteins in the intravascular sequestration of pulmonary neutrophils. Neutrophils were isolated from normal dogs and from the only living dog known to have leukocyte adhesion deficiency disease, an inherited deficiency of the CD11/CD18 adhesion family. The neutrophils were labeled with fluorescein dye, injected into normal recipient dogs, and their passage through the pulmonary microcirculation was recorded by in vivo videofluorescence microscopy through a transparent thoracic window. Transit times for normal and deficient neutrophils were similar over a wide range of hemo-dynamic conditions. Activation by zymosan-activated plasma, which increases the surface membrane expression of CD11/CD18, prolonged the transit of normal neutrophils but did not alter the transit time of the deficient neutrophils. These results indicate that neutrophil CD11/CD18 adhesion-promoting glycoproteins are not involved in the normal pulmonary sequestration of neutrophils but have a significant role in the arrest of activated neutrophils in the pulmonary capillaries.

Animals↗

Delayed presentation of a right-sided diaphragmatic hernia and group B streptococcal sepsis. Two case reports and a review of the literature.

Group B streptococcal sepsis was associated with delayed presentation of an unsuspected right-sided diaphragmatic hernia in two neonates. These unusual clinical observations and a review of 24 similar cases from the literature form the basis of this report. Infants present with respiratory distress during the first few hours of life and have group B streptococcal sepsis confirmed by results of blood cultures. The right side of the diaphragm appears normal on the initial chest roentgenogram in the majority of cases. After initial improvement with antibiotic therapy and ventilatory support, sudden deterioration of respiratory status may occur. Subsequent chest roentgenograms often demonstrate herniated viscera in half of the cases, while ultrasound examination, isotopic liver scan, and peritoneography are useful in achieving a diagnosis in the other cases. If recognized, survival is 100% following hernia repair. Persistent respiratory symptoms in a neonate who is recovering from group B streptococcal sepsis should prompt a careful evaluation of the right side of the diaphragm for the presence of an unsuspected posterolateral hernia.

Hernia, Diaphragmatic↗

Fibronectin turnover in the premature neonate measured with [15N]glycine.

Fibronectin is a large-molecular-weight glycoprotein present on most cell surfaces and in plasma. Plasma fibronectin concentrations in neonates are lower than those in adults and a direct relationship exists between plasma concentration and gestational age. We determined the half-life and fractional synthetic rate (FSR) of plasma fibronectin in the premature infant. Infants and adults received a loading dose of [15N]glycine followed by a constant infusion [15N]glycine incorporation into plasma fibronectin and urine hippurate was determined by gas chromatography-mass spectrometry. The plasma fibronectin FSR in the preterm neonates was 15.5 +/- 9.9%/d(means +/- SD) and the half-life was 5.55 +/- 2.25 d. Birth weight correlated inversely with plasma fibronectin half-life. In the adults the plasma fibronectin FSR ranged from 20 to 87%/d and half-life ranged between 0.79 and 3.47 d. These data suggest that decreased plasma fibronectin levels in preterm infants are due to reduced FSRs rather than to greater turnover of a relatively small plasma pool.

Adult↗

Culture medium oxygen tension affects fibronectin production in human adult and cord blood macrophages.

Varying culture medium oxygen tension from one-half to twice the normal concentration did not alter adult or cord blood monocyte-derived macrophage secretion of lysozyme or total protein. Lowering oxygen tension did result in significant increases in fibronectin concentration in both adult and cord blood macrophage culture supernatants. Dexamethasone (10(-7) M) completely blocked adult macrophage but had no effect on cord blood macrophage fibronectin release in response to lowering oxygen tension. These results indicate that human macrophages selectively regulate fibronectin production in response to changes in oxygen tension in vitro.

Adult↗

Vitamin E decreases superoxide anion production by polymorphonuclear leukocytes.

Pharmacologic serum levels of vitamin E administered to low birth weight infants predispose them to infectious complications. We studied in vitro the effect of vitamin E, its vehicle and buffer (Krebs Ringers phosphate glucose) on the ability of human polymorphonuclear leukocytes (PMN) to produce superoxide anion, an oxygen radical important for bacterial killing. We found that superoxide anion production after a 5-min exposure to phorbol myristate acetate was significantly decreased in vitamin E-treated PMN (76 +/- 15 nM/10(7) PMN) compared to vehicle-treated PMN (289 +/- 109 nM/10(7) PMN). We also found that significantly decreased superoxide anion production was associated with 5.0 and 10.0 mg/dl but not with 3.5 mg/dl vitamin E. Our results support the hypothesis that pharmacologic concentrations of vitamin E depress PMN oxidative activity.

Adult↗

Neonatal sepsis.

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Bacterial Infections↗

Enhanced endotoxin effects in plasma fibronectin-deficient rats.

Immunoreactive plasma fibronectin depletion has been associated with the presence of collagen-fibronectin complexes in patients after trauma and in animal models of traumatic and burn injuries. However, the role of plasma fibronectin in the development of sepsis after traumatic and burn injuries in patients is unknown. Treatment of patients and animals with purified human plasma fibronectin ameliorates some of the clinical and metabolic effects of systemic endotoxemia. We report that the induction of immunoreactive plasma fibronectin deficiency by gelatin infusion is associated with enhanced effects of intraperitoneal Escherichia coli endotoxin injection. We have observed a significant increase in the concentrations of ammonia in plasma of treated rats compared with those in control rats administered the same dose of endotoxin.

Ammonia↗