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Biomedical subjects

J M Greenberg

Publications and source records attributed to J M Greenberg.

At least 19 recordsLinked to original sources

VEGF causes pulmonary hemorrhage, hemosiderosis, and air space enlargement in neonatal mice.

To determine whether increased levels of VEGF disrupt postnatal lung formation or function, conditional transgenic mice in which VEGF 164 expression was enhanced in respiratory epithelial cells were produced. VEGF expression was induced in the lungs of VEGF transgenic pups with doxycycline from postnatal day 1 through 2 and 6 wk of age. VEGF levels were higher in bronchoalveolar lavage fluid (BALF) and lung homogenates of VEGF transgenic mice compared with endogenous VEGF levels in controls. Neonatal mortality was increased by 50% in VEGF transgenic mice. Total protein content in BALF was elevated in VEGF transgenic mice. Surfactant protein B protein expression was unaltered in VEGF transgenic mice. Although postnatal alveolar and vascular development were not disrupted by VEGF expression, VEGF transgenic mice developed pulmonary hemorrhage, alveolar remodeling, and macrophage accumulation as early as 2 wk of age. Electron microscopy demonstrated abnormal alveolar capillary endothelium in the VEGF transgenic mice. In many locations, the endothelium was discontinuous with segments of attenuated endothelial cells. Large numbers of hemosiderin-laden macrophages and varying degrees of emphysema were observed in adult VEGF transgenic mice. Overexpression of VEGF in the neonatal lung increased infant mortality and caused pulmonary hemorrhage, hemosiderosis, alveolar remodeling, and inflammation.

Aging↗

Amino acids from ultraviolet irradiation of interstellar ice analogues.

Amino acids are the essential molecular components of living organisms on Earth, but the proposed mechanisms for their spontaneous generation have been unable to account for their presence in Earth's early history. The delivery of extraterrestrial organic compounds has been proposed as an alternative to generation on Earth, and some amino acids have been found in several meteorites. Here we report the detection of amino acids in the room-temperature residue of an interstellar ice analogue that was ultraviolet-irradiated in a high vacuum at 12 K. We identified 16 amino acids; the chiral ones showed enantiomeric separation. Some of the identified amino acids are also found in meteorites. Our results demonstrate that the spontaneous generation of amino acids in the interstellar medium is possible, supporting the suggestion that prebiotic molecules could have been delivered to the early Earth by cometary dust, meteorites or interplanetary dust particles.

Amino Acids↗

In vitro model for developmental progression from vasculogenesis to angiogenesis with a murine endothelial precursor cell line, MFLM-4.

In the embryo, vascular networks are developed through both vasculogenesis, the assembly of vessels from endothelial progenitor cells or hemangioblasts, and angiogenesis, the sprouting of vessels from preexisting capillaries. Cell culture models using endothelial cells (EC) and various extracellular matrix components have been useful in understanding the cellular and molecular factors involved in angiogenesis. However, there are few models of vasculogenesis. Using a murine endothelial precursor cell line, MFLM-4, derived from e14.5 lung mesenchyme, we have developed a culture system that not only recapitulates many of the characteristics of vasculogenesis but also progresses into angiogenesis. By 8 h, MFLM-4 cultured on the basement membrane preparation Matrigel invade the matrix, coalesce, and assemble into large clusters of cells resembling blood islands. During vascular development, blood islands are the focal areas for coalescence of endothelial precursors. For MFLM-4, this phase of in vitro vasculogenic clustering does not require proliferation. If proliferation is not blocked, MFLM-4 progresses into an angiogenic phase with the clusters forming multicell angiogenic sprouts. Through 3 days of culture, lumens form within the clusters, adjacent clusters are connected with tube-like structures, and eventually an extensive network or plexus of clusters connected by capillary-like tubes is formed. MFLM-4 cultured on Matrigel provides an in vitro system for analysis of the multistage, concurrent processes of vasculogenesis and angiogenesis.

Animals↗

Simulated cometary matter as a test for enantiomer separating chromatography for use on comet 46P/Wirtanen.

The Cometary Sampling and Composition Experiment on board of European Space Agency's cornerstone mission ROSETTA is designed to identify organic molecules in cometary matter in situ by a combined pyrolysis gas chromatographic and mass spectrometric technique. Its capillary columns coated with chiral stationary phases received considerable attention, because they are designed for separations of non-complex enantiomers to allow the determination of enantiomeric ratios of cometary chiral organic compounds and consequently to provide information about the origin of molecular parity violation in biomolecules. To get gas chromatographic access to organic compounds on the comet, where macromolecules and complex organic polymers of low volatility are expected to make up the main organic ingredients, the combination of two injection techniques will be applied. The pyrolysis technique performed by heating cometary samples stepwise to defined temperatures in specific ovens resulting in thermochemolysis reactions of polymers and a chemical derivatization technique, in which the reagent dimethylformamide dimethylacetal assists pyrolysis derivatization reactions in producing methyl esters of polar monomers. The combination of the reagent assisted pyrolysis gas chromatographic technique with enantiomer separating chromatography was tested with laboratory-produced simulated cometary matter.

Ammonia↗

A feeding protocol for healthy preterm infants that shortens time to oral feeding.

OBJECTIVE: To test the hypothesis that healthy preterm infants randomly assigned to a semi-demand feeding protocol would require fewer days to attain oral feeding and have a satisfactory weight gain compared with control infants receiving standard care. STUDY DESIGN: In 2 neonatal intensive care nurseries, 81 infants 32 to < or = 34 weeks' postconceptional age were randomly assigned to the control (n = 41) or experimental (n = 40) protocol for transition from gavage to oral feedings. The control protocol followed the standard practice of gradually increasing scheduled oral feedings, whereas the experimental protocol used a semi-demand feeding method contingent on infant behavior. Analysis of variance techniques were used to compare the study groups for number of days to attain oral feeding and weight gain. RESULTS: The semi-demand method shortened the time for infants to achieve oral feeding by 5 days (P < .001). There were no differences in weight gain between the study groups, and both groups had satisfactory weight gain. CONCLUSION: The semi-demand method for the transition from gavage to oral feeding in healthy, preterm infants 32 to < or = 34 weeks postconceptional age promotes faster attainment of oral feeding and does not compromise their weight gain.

Administration, Oral↗

Embryonic vasculogenesis by endothelial precursor cells derived from lung mesenchyme.

During development, the lung mesenchyme has a dynamic relationship with the branching airway. Embryonic lung mesenchyme is loosely packed and composed of indistinguishable cells, yet it is the source of vascular progenitors that will become endothelial cells, smooth muscle cells and fibroblasts. In the lung, vessel development in the periphery proceeds first through vasculogenesis, the migration and assembly of cells into a primitive network, and subsequently, through angiogenesis, the sprouting of vessels from this network. As a way to assess the cellular and molecular mechanisms of lung vascularization, we have isolated and cloned cell lines from mouse fetal lung mesenchyme (MFLM). Two of these MFLM cell lines, MFLM-4 and MFLM-91U, display characteristics of an endothelial lineage. RNA analysis demonstrates transcripts for the vascular endothelial growth factor receptors R1 and R2, the receptor tyrosine kinases, Tie-1 and Tie-2, as well as the Tie-2 ligands, Ang-1 and -2. The MFLM cell lines form extensive networks of capillary-like structures with lumens when cultured on a reconstituted basement membrane. In vivo, following blastocyst injection, the MFLM cells chimerize endothelium of the lung and areas of the heart vasculature. The results from these studies suggest that MFLM-4 and MFLM-91U, derived from embryonic lung mesenchyme, can function in vitro and in vivo as endothelial precursors and as models of cardiopulmonary vascularization. Dev Dyn 2000;217:11-23.

Animals↗

Tracking the organic refractory component from interstellar dust to comets.

The abundance and composition of complex organic (carbonaceous) material in the interstellar dust is followed as the dust evolves in its cyclic evolution between diffuse and dense clouds. Interstellar extinction, laboratory and space analog experiments, dust infrared absorption spectra, the cosmic abundance of the condensible atoms, and space and ground-based observations of comet dust are used to impose constraints on the organic dust component as mantles on silicate cores.

Carbon↗

The extraterrestrial origin of the homochirality of biomolecules--rebuttal to a critique.

Having concluded that abiotic terrestrial mechanisms would have been ineffectual for the origin of terrestrial homochirality, we have proposed an alternative extraterrestrial scenario involving stereoselective ultraviolet photolysis of the racemic constituents of interstellar grain mantles by circularly polarized synchrotron radiation from neutron stars, followed by terrestrial accretion of the resulting chiral molecules via cometary impact. Recently L. Keszthelyi (1995) has reviewed a number of our arguments and advanced several erroneous calculations and conclusions purporting to negate them. We offer here points of rebuttal to Keszthelyi's criticisms, and support our inferences with recent data regarding indigenous enantiomeric excesses of L-amino acids in the Murchison meteorite.

Amino Acids↗

Alveolar capillary dysplasia with misalignment of the pulmonary veins: a rare but fatal cause of neonatal respiratory failure.

Respiratory failure in the neonate that is refractory to maximal medical management is a frequent indication for extracorporeal life support (ECLS). Alveolar capillary dysplasia with misalignment of the pulmonary veins is an irreversible cause of respiratory failure that cannot be diagnosed on clinical grounds alone and would not be expected to respond to ECLS therapy. A recent experience with a patient prompted us to review the literature regarding this condition for the purpose of identifying factors suggestive of this diagnosis. This condition should be considered in neonates with presumed pulmonary hypertension who cannot be weaned from ECLS. If the diagnosis is made by antemortem open-lung biopsy, a costly, protracted, and unnecessary continued course of ECLS may be avoided.

Capillaries↗

Evolution of interstellar dust and its relevance to life's origin: laboratory and space experiments.

A scheme is presented for an analog investigation of long term irradiation of ices and organics following the cyclic evolution of interstellar dust. The irradiation is proposed to be performed at cryogenic temperatures on a space platform, and with an enhancement of the solar ultraviolet flux using a concave mirror, grating combination which eliminates the visual and infrared from the sample surface.

Carbon↗

Comets as porous aggregates of interstellar dust.

A comet model is derived based on the interstellar dust chemical composition in dense molecular and diffuse clouds resulting from their subsequent chemical interactions and UV photoprocessing. The collapsing presolar nebula leads to a porous aggregate model for comet nuclei, from which is derived certain physical properties that include thermal conductivity and tensile strength. The porous morphological structure is also shown to imply anomalous (expansion rather than contraction) behavior when subjected to strong shock waves, which is supported by recent shock experiments on (porous) carbonaceous chondrite material.

Cosmic Dust↗

From the interstellar clouds, through the inner to the outer solar system: a universally distributed complex organic chemistry. Preface.

High molecular weight organic compounds are involved in the chemistry and physics of many astrophysical and planetary objects. They are or should be present in interstellar dust, in comets and meteorites, in the Giant planets and Titan, in asteroids Triton and icy satellites. They represent a class of very complex organic material, part of which may have played a role in the origin of life on Earth. Thus they directly concern prebiotic chemistry and exobiology.

Cosmic Dust↗

Silicate core-organic refractory mantle particles as interstellar dust and as aggregated in comets and stellar disks.

The principal observational properties of silicate core-organic refractory mantle interstellar dust grains in the infrared at 3.4 microns and at 10 microns and 20 microns are discussed in terms of the cyclic evolution of particles forming in stellar atmospheres and undergoing subsequent accretion, photoprocessing and destruction (erosion). Laboratory plus space emulation of the photoprocessing of laboratory analog ices and refractories are discussed. The aggregated interstellar dust model of comets is summarized. The same properties required to explain the temperature and infrared properties of comet coma dust are shown to be needed to account for the infrared silicate and continuum emission of the beta Pictoris disk as produced by a cloud of comets orbiting the star.

Cosmic Dust↗

Homochirality as the signature of life: the SETH Cigar.

A characteristic hallmark of life is its homochirality: all biomolecules are usually of one hand, e.g. on Earth life uses only L-amino acids for protein synthesis and not their D mirror images. It is therefore suggested that a search for extra-terrestrial life can be approached as a Search for Extra-Terrestrial Homochirality (SETH). A novel miniaturized space polarimeter, called the SETH Cigar, is described which could he used to detect optical rotation as the homochiral signature of life on other planets. Moving parts are avoided by replacing the normal rotating polarizer by multiple fixed polarizers at different angles as in the eye of the bee. It is believed that homochirality will be found in the subsurface layers on Mars as a relic of extinct life.

Astronomy↗

Expression of receptor protein tyrosine kinase tif is regulated during leukemia cell differentiation.

tif is a recently cloned and characterized cDNA predicting a transmembrane protein with a putative tyrosine kinase structure in its cytoplasmic domain. By analysis of the purified tif cytoplasmic domain expressed in Escherichia coli, we have demonstrated that tif is an active protein tyrosine kinase capable of autophosphorylation on tyrosine residues and this phosphorylation is inhibited by a tyrosine-specific inhibitor genistein. Northern blot analyses of various leukemia cell lines have revealed that tif mRNA expression is primarily confined to those bearing erythroid and megakaryocytic phenotypes. Megakaryocytic differentiation of K562 and HEL cells induced by phorbol 12-myristate 13-acetate is accompanied by down-regulation of tif mRNA expression. In addition, treatment of K562 and HEL with hexamethylene bis-acetamide, but not with hemin, decreases the steady-state level of tif mRNA. These combined results suggest that the receptor tyrosine kinase tif is involved in hematopoietic development.

Acetamides↗

Understanding why heterosexual adults do not practice safer sex: a comparison of two samples.

We assessed why heterosexually active adults did not have "safer sex" with their last sexual partner. Subjects enrolled in HIV education and testing trials at a sexually transmitted disease (STD) clinic and a university student health service (SHS) completed questionnaires about their last sexual partner's risk factors for HIV and whether they had safer sex with this partner. Of the 652 sexually active subjects, 61% reported not having safer sex with their last sexual partner and explained why. Low perceived risk of HIV infection was the most common reason, indicated by 62%, though most knew too little about their partner to ensure the encounter was low risk. Other reasons included condom unavailability (20%), the subject "didn't want to" use a condom (19%), "couldn't stop ourselves" (15%), the partner's influence (14%), and alcohol or drug use (11%). Thirty-one percent of subjects indicated more than one reason for not having safer sex. SHS subjects more often reported that the encounter was low risk for HIV transmission (p = 0.0001), while STD subjects more often reported condom unavailability (p = 0.002) and drug and alcohol use (p = 0.003). We conclude that there are many different factors promoting sexual behavior at risk of infection, combinations of which are important, and that these factors differ between samples. Preventive interventions must focus on the factors most important to the targeted population and may need to consider multiple factors simultaneously.

Acquired Immunodeficiency Syndrome↗

Origin of organic matter in the protosolar nebula and in comets.

Comet organics are traced to their origin in interstellar space. Possible sources of comet organics from solar nebula chemistry are briefly discussed. The infrared spectra of interstellar dust are compared with spectra of solar (space) irradiated laboratory organic residues and with meteorites. The spectra compare very favorably. The atomic composition of first generation laboratory organic residues compares favorably with that of comet Halley organics if divided into appropriate "volatile" (less refractory) and "refractory" (more refractory) complex organics.

Cosmic Dust↗