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Biomedical subjects

C L Stewart

Publications and source records attributed to C L Stewart.

At least 55 records · Page 3Linked to original sources
PubMed1995

Leukemia inhibitory factor influences the timing of programmed synapses withdrawal from neonatal muscles.

We show that leukemia inhibitory factor (LIF) plays a physiological role in the programmed withdrawal of synapses from neonatal muscles. First, LIF mRNA is present in embryonic skeletal muscle and is developmentally regulated. We detect high levels of LIF mRNA at embryonic day 17 (E17) in mouse hind leg muscles. The content of LIF mRNA falls 10-fold between E17 and birth and then remains low in the neonate and adult. The decrease in LIF mRNA in skeletal muscle coincides with the end of secondary myogenesis and the completion of the adult number of myofibers. Second, treatment of the mouse tensor fascia latae (TFL), a superficial muscle of the hind leg, with LIF from birth (100 ng/day), transiently delays the withdrawal of excess inputs from polyneuronally innervated myofibers by approximately 3 days. The midpoint of the process is shifted from 7.5 +/- 10.2 +/- 0.6 days of age. LIF treatment delays synapse withdrawal by altering its timing without an appreciable effect on its rate. Third, in mice homozygous for a disruption of the LIF gene, the midpoint in the reduction of multiply innervated TFL myofibers occurs 1 day earlier, at 6.5 +/- 0.5 days of age. Muscle fiber number is unchanged in LIF null mice. Treatment with LIF does not alter the rate of neonatal growth, the number of muscle fibers in the TFL, or the reappearance of inputs that have been eliminated. Instead, LIF appears to delay maturation of the motor unit by transiently delaying the onset of synapse withdrawal. We hypothesize that this is a necessary component of a selective process that will operate simultaneously and equally on multiple, competing motor units.

Animals↗
PubMed1995

Megacystis-microcolon-intestinal hypoperistalsis syndrome.

The megacystis-microcolon-intestinal hypoperistalsis syndrome is a congenital disorder characterized by urinary bladder distension and hypoperistalsis throughout the entire gastrointestinal tract. We present a new case with the typical clinical, radiological, and pathological findings of the syndrome. The diagnosis should be suspected in a patient who present clinically with intestinal obstruction and urinary retention, and confirmed with imaging studies, including abdominal plain films, urinary tract ultrasonography, and contrast studies of the colon and the bladder. The prognosis is generally very poor. Our patient died secondary to sepsis on day 5 of life.

Abnormalities, Multiple↗
PubMed1995

Acid sphingomyelinase deficient mice: a model of types A and B Niemann-Pick disease.

Types A and B Niemann-Pick disease (NPD) result from the deficient activity of acid sphingomyelinase (ASM). An animal model of NPD has been created by gene targeting. In affected animals, the disease followed a severe, neurodegenerative course and death occurred by eight months of age. Analysis of these animals showed their tissues had no detectable ASM activity, the blood cholesterol levels and sphingomyelin in the liver and brain were elevated, and atrophy of the cerebellum and marked deficiency of Purkinje cells was evident. Microscopic analysis revealed 'NPD cells' in reticuloendothelial organs and characteristic NPD lesions in the brain. Thus, the ASM deficient mice should be of great value for studying the pathogenesis and treatment of NPD, and for investigations into the role of ASM in signal transduction and apoptosis.

Animals↗
PubMed1995

Defective development of the embryonic and extraembryonic circulatory systems in vascular cell adhesion molecule (VCAM-1) deficient mice.

VCAM-1 is a cytokine-inducible cell surface protein capable of mediating adhesion to leukocytes expressing alpha 4 integrins. Mice deficient in VCAM-1 expression were produced by targeted homologous recombination in ES cells. VCAM-1-deficient embryos were not viable and exhibited either of two distinct phenotypes. Approximately half of the embryos died before embryonic day 11.5 and exhibited a severe defect in placental development in which the allantois failed to fuse with the chorion. The remaining VCAM-1-deficient embryos survived to embryonic day 11.5-12.5 and displayed several abnormalities in their developing hearts including a reduction of the compact layer of the ventricular myocardium and intraventricular septum. The hearts also contained significant amounts of blood in the pericardial space and lacked an epicardium. alpha 4 and VCAM-1 were found to be expressed in wild-type embryos in a reciprocal fashion in the chorion and allantois and in the epicardium and the underlying myocardium, although VCAM-1 was expressed in the intraventricular septum in the absence of adjacent alpha 4-expressing cells. These data suggest important roles for VCAM-1 and alpha 4 in the development of the placenta and the heart.

Allantois↗
PubMed1995

[Regulation by maternally derived cytokines of pre-implantation development and uterine receptiveness].

Increasing evidence is revealing that cytokines, under the control of steroid hormones, are important in regulating fetal-maternal interactions during pregnancy. Mice carrying mutated genes coding for these factors or their receptors, have been instrumental in clarifying the in vivo roles of these factors in reproduction. Lack of many of the cytokines expressed in the male and female reproductive tracts, such as TNF-alpha, Inf-gamma, the majority of the interleukins and the transforming growth factors TGF-alpha and beta do not result in any gross impairment in reproductive efficiency. However, some cytokines do have a critical role, in particular Leukemia Inhibitory Factor (LIF), Colony stimulating Factor-1 (CSF-1), Epidermal Growth Factor (EGF) and possibly interleukin-1 (IL-1). The recent advances relating to the reproductive roles of these factors up to the time of embryo implantation will be discussed.

Animals↗
PubMed1994

Loss of the imprinted IGF2/cation-independent mannose 6-phosphate receptor results in fetal overgrowth and perinatal lethality.

Murine embryos that inherit a nonfunctional insulin-like growth factor-II/cation-independent mannose 6-phosphate receptor (Igf2r) gene from their fathers are viable and develop normally into adults. However, the majority of mice inheriting the same mutated allele from their mothers die around birth, as a consequence of major cardiac abnormalities. These mice do not express IGF2R in their tissues, are 25-30% larger than their normal siblings, have elevated levels of circulating IGF2 and IGF-binding proteins, and exhibit a slight kink in their tails. These results show that Igf2r is paternally imprinted and reveal that the receptor is crucial for regulating normal fetal growth, circulating levels of IGF2, and heart development.

Alleles↗
PubMed1994

Leukaemia inhibitory factor and the regulation of pre-implantation development of the mammalian embryo.

This paper reviews the evidence that certain growth factors, particularly leukaemia inhibitory factor (LIF), play a crucial role in regulating the development of the pre-implantation mammalian embryo. LIF was originally implicated in regulating the early development of the mouse embryo because it inhibited the differentiation of embryonic stem (ES) cells, pluripotential cells derived from the inner cell mass of the blastocyst. Subsequent studies on its role in vivo revealed, surprisingly, that it is essential for the growth rather than the differentiation of the blastocyst. In vivo, overtly normal blastocysts can be produced in a LIF-deficient environment that are capable of forming viable fertile adults. However, in the absence of LIF, they fail to implant and enter into a state resembling that exhibited by blastocysts undergoing delayed implantation, which is characterized by a cessation of cell proliferation. This failure to implant occurs because the principle sites of LIF production are the endometrial glands of the uterus. These synthesize and secrete LIF at implantation, with LIF synthesis essential for implantation. Preliminary evidence indicates that LIF synthesis is required both by the uterus for it to undergo decidualization and by the blastocyst for implantation. These data indicate that the maternal environment plays a crucial role in the development and growth of the pre-implantation embryo, by supplying factors that regulate these processes in the embryo.

Animals↗
PubMed1994

Stem cells from primordial germ cells can reenter the germ line.

Embryonic stem (ES) cells are totipotent cells derived from cultured preimplantation blastocysts. When injected into embryos, they can give rise to all somatic lineages as well as functional gametes. Embryonal carcinoma (EC) cells are pluripotent cells, derived from teratocarcinomas, which contribute to somatic lineages, but only rarely to the germ line. A novel source of pluripotent cells, remarkably similar to both ES and EC cells, has been identified. These are EG cells, derived by culturing primordial germ cells isolated from postimplantation embryos, but it is not known whether they resemble ES or EC cells in their ability to contribute to the germ line. Here we show that EG cells of both sexes can form functional gametes. The derivation of such cell lines offers a new route to deriving totipotent cells and also provides insights into the timing of X-chromosome inactivation/activation and genomic imprinting in the germ line.

Animals↗
PubMed1994

Targeted disruption of NMDA receptor 1 gene abolishes NMDA response and results in neonatal death.

In vitro studies have suggested that the NMDA receptor consists of an essential subunit, NR1, and various modulatory NR2 subunits. To test this hypothesis directly in vivo, we generated mice carrying a disrupted NR1 allele. NMDA-inducible increases in intracellular calcium and membrane currents were abolished in neurons from homozygous null mutants (NR1-/-). Thus, NR1 has a unique role, which cannot be substituted by any other subunit, in determining the activity of the endogenous NMDA receptor. A concomitant reduction in levels of NR2B but not NR2A occurred in NR1-/- mice, demonstrating that there is an interdependence of subunit expression. NR1-/- mice died 8-15 hr after birth, indicating a vital neonatal function for the NMDA receptor. Although the NMDA receptor has been implicated in several aspects of neurodevelopment, overall neuroanatomy of NR1-/- mice appeared normal. Pathological evidence suggested that respiratory failure was the ultimate cause of death.

Animals↗
PubMed1993

IgG and IgA classes of anti-neutrophil cytoplasmic autoantibodies in a 13-year-old girl with recurrent Henoch-Schonlein purpura.

We describe a 13-year-old girl with recurrent Henoch-Schonlein purpura whose symptoms were precipitated by upper respiratory tract infections. Her serum was positive for both IgG and IgA classes of anti-neutrophil cytoplasmic autoantibodies by immunofluorescence. The titers of both autoantibodies correlated with disease activity. The immunopathology underlying these findings is discussed.

Adolescent↗
PubMed1993

Effect of an ultrasonic device on temperatures generated in bone and on bone-cement structure.

Cement removal during revision arthroplasty can be a tedious, time-consuming process. The usual methods of removing cement include high-speed drills, chisels, saws and reamers, which are often associated with fracture and/or perforation of the femoral shaft. Ultrasound has been used in dentistry to remove plaque and in ophthalmology to remove cataracts and is now applied to cement removal in orthopaedic surgery. There is little data available on the effect of ultrasound on temperatures generated in bone and on its effects on the structure of bone-cement. A cement mantle was constructed in the intramedullary canal in each of six 10 cm lengths of human cadaver femora. A temperature probe was then inserted into predrilled holes and temperatures generated by the ultrasonic device were recorded under a variety of conditions. In addition, a cement cylinder was microscopically evaluated after an ultrasonic tool had been inserted. Temperatures generated by the ultrasonic tool in cadaver bone were no higher than previously reported temperatures of 140 degrees C generated by high-speed drills. Furthermore, temperatures at the bone-cement interface never exceeded 60 degrees C when saline irrigation was used in conjunction with the ultrasonic tools, and were below 40 degrees C 1 minute after deactivation of the device. Microscopic examination shows that ultrasound produced local changes in the structure of bone-cement converting it from a microscopically spherical interlocked material to one that appears homogeneous and granular.

Bone Cements↗