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Biomedical subjects

J Stone

Publications and source records attributed to J Stone.

At least 163 records · Page 9Linked to original sources
PubMed1995

Multifetal pregnancy reduction and selective termination.

The incidence of multifetal pregnancies has increased dramatically since the advent of assisted reproductive technologies. Preterm delivery accounts for most of the mortality associated with multifetal pregnancies. Multifetal pregnancy reduction is a safe and effective procedure designed to decrease the adverse outcomes associated with very preterm deliveries. The increased incidence of multifetal pregnancies combined with reliable techniques for prenatal diagnosis of genetic and structural fetal anomalies have led to an increase in the diagnosis of abnormal fetal conditions in parents carrying multiple gestations. The development of the procedure of selective termination has provided prospective couples the option of selective termination of the abnormal fetus and continuation of the pregnancy.

Chorion↗
PubMed1995

Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and has implications for retinopathy of prematurity.

Retinopathy of prematurity (ROP) is initiated by hyperoxia-induced obliteration of newly formed blood vessels in the retina of the premature newborn. We propose that vessel regression is a consequence of hyperoxia-induced withdrawal of a critical vascular survival factor. We show that regression of retinal capillaries in neonatal rats exposed to high oxygen, is preceded by a shut-off of vascular endothelial growth factor (VEGF) production by nearby neuroglial cells. Vessel regression occurs via selective apoptosis of endothelial cells. Intraocular injection of VEGF at the onset of experimental hyperoxia prevents apoptotic death of endothelial cells and rescues the retinal vasculature. These findings provide evidence for a specific angiogenic factor acting as a vascular survival factor in vivo. The system also provides a paradigm for vascular remodelling as an adaptive response to an increase in oxygen tension and suggests a novel approach to prevention of ROP.

Animals↗
PubMed1995

The packaging phenotype of the SE21Q1b provirus is related to high proviral expression and not trans-acting factors.

The avian packaging cell line SE21Q1b produces particles which encapsidate cellular RNAs. Such RNAs can be reverse transcribed by endogenous polymerase and integrated into the genomes of newly infected cells (M. Linial, Cell 49:93-102, 1987). Genomic RNA is not packaged because the packaging (psi) region of the provirus is deleted. The provirus also lacks the negative-strand primer binding site, which prevents efficient reverse transcription of randomly packaged genomic RNA. Previous work from our laboratory suggested that the trans-acting defect which allows packaging of cellular mRNA mapped to the provirus but did not map to the nucleocapsid region of the gag gene (D.J. Anderson, P. Lee, K. L. Levine, J. Sang, S. A. Shah, O. O. Yang, P. R. Shank, and M. L. Linial, J. Virol. 66:204-216, 1992). We have found, using proviral recombinants between SE21Q1b and wild-type Rous sarcoma virus, that packaging of cellular RNAs does not map to the gag gene. Rather, the propensity of SE21Q1b particles to package cellular mRNA is a function of the high level of particle production in these cells and not of any specific viral structural proteins.

Amino Acid Sequence↗
PubMed1995

Evidence of constriction of optic nerve axons at the lamina cribrosa in the normotensive eye in humans and other mammals.

The ultrastructure of optic nerve axons was examined in several mammals (human, cat, rat, sheep, ox, pig, guinea pig, rabbit). Human material was obtained from normotensive, glaucoma-free eyes and from eyes with a history of glaucoma and raised intra-ocular pressure (IOP). We describe accumulations of organelles (principally mitochondria) in optic nerve axons where they traverse the lamina cribrosa. Accumulations were most prominent in unmyelinated lengths of axons close to lamellae of the lamina cribrosa. Comparable accumulations were not apparent in axons in the retina or optic nerve, suggesting that axoplasmic flow is constricted at the lamina cribrosa. Accumulations were observed both centrally and peripherally to the lamellae, suggesting that flow is constricted in both ortho- and anterograde directions. Accumulations of organelles were more marked in unmyelinated axons than in adjacent, myelinated axons. In the rabbit, in which most axons are myelinated as they traverse the optic nerve head, organelle accumulations were observed only in a sparse population of unmyelinated axons. In human eyes with a history of raised IOP and glaucoma, the accumulations were abnormally large and frequent and in many axons showed dense-body and fibrillar changes not seen in normotensive eyes. It is suggested that chronic, partial constriction of axoplasmic flow is present at the lamina cribrosa of normotensive eyes in a wide range of mammals, including humans, that the constriction results from the pressure gradient across the lamina cribrosa and that the constriction may be a factor in the many cases of primary glaucoma in which IOP is not raised.

Adult↗
PubMed1995

Development of retinal vasculature is mediated by hypoxia-induced vascular endothelial growth factor (VEGF) expression by neuroglia.

We have studied the role of the hypoxia-inducible angiogenic growth factor vascular endothelial growth factor (VEGF) in the induction and control of vessel growth in the developing retina of rats and cats, using in situ hybridization techniques. VEGF is expressed successively in two layers of neural retina, the innermost (axon) layer and the inner nuclear layer (INL). In the axon layer, VEGF is expressed transiently by astrocytes as they spread across the layer, closely preceding the formation of superficial vessels. In the INL, VEGF is expressed transiently by somas at the middle of the layer (presumably Müller cells), closely preceding the formation of the deep layer of retinal vessels. We propose that hypoxia caused by the onset of neuronal activity is detected by strategically located populations of neuroglia, first astrocytes, then Müller cells. In response they secrete VEGF, inducing formation of the superficial and deep layers of retinal vessels, respectively. As the vessels become patent, they relieve the hypoxic stimulus, so vessel formation is matched to oxygen demand. This hypothesis was tested experimentally in three ways. Expression of the high affinity flk-1 receptor for VEGF was demonstrated in newly formed retinal vessels, confirming that the secreted VEGF acts on the vessels, in a paracrine fashion. Direct hypoxic regulation of VEGF expression by macroglia was demonstrated in primary cultures of astrocytes and in cells of a glioma line. Hypoxic regulation of VEGF expression in the intact developing retina was demonstrated by showing that oxygen-enriched atmospheres that inhibit vessel formation also suppress endogenous VEGF production.

Animals↗
PubMed1995

The effect of oxygen on vasoformative cell division. Evidence that 'physiological hypoxia' is the stimulus for normal retinal vasculogenesis.

PURPOSE: To assess the role of oxygen in normal retinal vasculogenesis. METHODS: A new preparation for studying cytogenesis in retinal wholemounts was developed. Nuclei of dividing cells were labeled with a monoclonal antibody to bromodeoxyuridine (BrdU), and vascular cells were covisualized with Griffonia simplicifolia lectin. The topography and time course of vasculogenic cell division and vessel formation were determined in the kitten retina during normal development and under experimental hyperoxia and hypoxia. RESULTS: During normal development, vasculogenic cell division was maximal at the leading edge of the forming vessels. Normal vessel formation was initially proliferative, and cell division was high. However, after vessel formation occurred, which presumably relieved tissue hypoxia, the mitogenic process was markedly reduced, and many excess capillary segments underwent retraction. The rate of vasculogenic cell division and vessel formation increased when the inner layers of the retina were made avascular after exposure to hyperoxia, and it decreased when there was an increase in inspired oxygen. CONCLUSIONS: The authors have shown that between 17% and 45% oxygen, the extent of vasculogenic cell division is inversely proportional to the level of oxygen in the inspired gas mixture. They have further shown that dividing vascular cells have a peak density in a region proximal to the edge of the forming vasculature. The density is maximal between P7 and P8, a time when formation of photoreceptor outer segment begins, only a few days before the onset of retinal function. These results led the authors to conclude that the stimulus for normal vasculogenesis is a transient but physiological level of hypoxia induced by the increasing activity of retinal neurons.

Animals↗
PubMed1995

Supplemental oxygen therapy. Basis for noninvasive treatment of retinopathy of prematurity.

PURPOSE: To determine the effectiveness of supplemental oxygen therapy (SOT) in ameliorating the proliferative vasculopathy characteristic of the feline model of retinopathy of prematurity (ROP). METHODS: Kittens were exposed to high (70% to 80%) oxygen for the first 4 days of life to induce obliteration of the retinal circulation. The level of inspired oxygen at successive stages after hyperoxia were varied systematically, and the retinas were examined for the extent of revascularization, astrocyte survival, intactness of the blood-retinal barrier, and extent of preretinal vessels. RESULTS: The level of inspired oxygen required to protect the retina from hypoxic damage and yet provide a stimulus for growth of the vasculature varied during a 6-week period. The rate of revascularization of the retina increased as the oxygen content of the inspired gas mixture decreased, with a consequential increase in the pathology observed. However, a regimen that produced a quicker rate of revascularization with a slightly higher level of pathology actually offered the retina greater protection in the long term. The formation of preretinal vessels was effectively prevented by SOT. Supplemental oxygen therapy could be terminated once a significant portion of the retina was revascularized. CONCLUSIONS: The proliferative vasculopathy of a kitten model of ROP can be significantly reduced by a regimen of SOT, which attempts to mimic physiological levels of hypoxia in the retina during its revascularization. Optimal revascularization requires a balance between the rate and quality of vessel growth. With further refinement of the protocol, SOT could provide noninvasive treatment of ROP in neonates.

Animals↗
PubMed1994

Interactions of living astrocytes in vitro: evidence of the development of contact spacing.

We have studied the behaviour of living, process-bearing astrocytes in vitro, observing groups of cells at daily intervals for up to 7 days. Each cell initially formed two processes, appearing bipolar in shape, and with further time in culture, grew additional processes and appeared stellate. As their processes grew, the interactions between astrocytes underwent characteristic changes. While bipolar, the cells appeared to avoid making contact, lying parallel to each other. As they became stellate, the astrocytes made extensive contact with neighbours, gradually forming extended, contacting networks in which their somas were regularly spaced (as previously described). The interactions which led to the establishing of such arrays were also evident. If two cells were initially close or adjacent, they extended short processes to contact each other; then, as their processes grew, their somas moved apart, until they were separated by 60-120 microns. If two cells were initially well separated, each directed processes towards the other until contact was made, often with striking precision, and their somas then moved together, until they were separated by 60-120 microns. These behaviours of contact, separation, and approach caused astrocytes to form clusters, within which their somas appeared regularly spaced, and may represent the interactions which occur among astrocytes during normal development to produce the regularly spaced arrays of astrocytes described in earlier studies of intact central nervous tissue.

Animals↗
PubMed1994

Breast implant endoscopy. Detecting leaks in silicone-gel breast implants.

Until the development of implant endoscopy, the only method available to evaluate silicone-gel breast implants accurately for silicone leaks involved making a wide incision and visually inspecting the implant. Endoscopic magnification, however, allows an accurate diagnosis to be achieved rapidly and safely by using a tiny incision that does not endanger the implant. As breast implant endoscopy becomes more common, perioperative nurses should be able to discuss the procedure with patients. The information provided in this article is intended to educate nurses on the procedure and prepare them to counsel patients undergoing the procedure.

Endoscopy↗
PubMed1994

Neuropsychological functioning in older insomniacs with or without obstructive sleep apnea.

The relationships between neuropsychological functioning and sleep loss, sleep apnea, and hypoxemia were examined. Forty-five older insomniacs (M age = 64.6 years) with or without sleep apnea were administered neuropsychological tests after 1 night of nocturnal monitoring in a sleep laboratory. The results showed few differences on cognitive and psychomotor performance between individuals with sleep disruptions alone compared with those whose insomnia was associated with sleep apnea and hypoxemia. There were no significant relationships between nocturnal sleep and respiratory variables and daytime functioning. Furthermore, cognitive and psychomotor performance in older insomniacs with or without sleep apnea revealed minimal impairment compared with age-matched normative data. The results suggest that when the severity of sleep disruptions is controlled, there are minimal differences in neuropsychological functioning of older adults with mild to moderate sleep apnea compared with those without apnea.

Aged↗
PubMed1994

Association of an estrogen receptor variant with increased height in women.

There is an association between a B region allele (here called the B' allele) of the estrogen receptor (ER) and a history of spontaneous abortion in women with ER positive breast cancer, but no such association for women with ER negative tumors or women without breast cancer. In this study we compared the heights of women carrying the B and B' alleles. The B' allele was identified by polymerase chain reaction to amplify genomic DNA around the polymorphic region of the ER gene, followed by allele specific oligonucleotide hybridization. This analysis used DNA obtained from blood lymphocytes. Women carrying the B' allele were significantly taller than those carrying the wild type allele (B allele). Multiple linear regression also demonstrated that this association remained (p = 0.017), controlling for the effects of age and race. Since the B' ER allele results from a silent mutation, a second mutation, segregating with it, no doubt plays a role in producing the high incidence of spontaneous abortion we reported previously and the height difference we report here. This second mutation might lie within the estrogen receptor itself or within one of the genes nearby.

Adolescent↗
PubMed1994

Multifetal pregnancy: risks and methods of reduction.

Multifetal pregnancy reduction offers an acceptable option to patients faced with the significant risk of long-term morbidity associated with multifetal gestation, especially gestation involving 4 or more fetuses. Until advances in reproductive technology eliminate the iatrogenic occurrence of multifetal gestation, and until progress in perinatal care decreases the threat of preterm delivery, multifetal pregnancy reduction offers hope for a good outcome in an otherwise dismal situation.

Female↗
PubMed1994

Wide-band transabdominal cerclage for a foreshortened, incompetent cervix.

BACKGROUND: The role of cervical cerclage in the prevention of fetal wastage due to cervical incompetence is well established. The transvaginal approach and, failing that, the transabdominal approach, provide sufficient treatment in most cases. However, the traditional techniques require adequate cervical length for placement and maintenance of the suture. CASE: We report a new technique used for a patient with a markedly foreshortened cervix and a history of multiple second-trimester pregnancy losses despite placement of McDonald cerclages. To improve the performance of the cervix, we included the lower portion of the uterus in a 3-cm-wide Prolene mesh cerclage. During the patient's subsequent pregnancy, the mesh band funneled the lower uterine segment, creating a functionally longer cervix. The patient successfully carried the pregnancy to term and was delivered by cesarean. CONCLUSION: This variation on the transabdominal approach is useful in the management of patients with cervical incompetence who demonstrate a foreshortened cervix incapable of maintaining a traditional cervical suture.

Adult↗
PubMed1993

Contact-spacing among astrocytes is independent of neighbouring structures: in vivo and in vitro evidence.

We have examined the morphology of astrocytes and the arrays they form in two situations, in retinas from which ganglion cells and blood vessels have been caused to degenerate, and in vitro. These observations were made to test whether the regularity of the spacing of astrocytes within normal central nervous tissue results from interaction among astrocytes, or from interaction between astrocytes and other elements of that tissue. Both in the partially degenerated cat retina, and in cultures of astrocytes from neonatal rat cortex, astrocytes make and maintain contact with neighbouring astrocytes, yet space their somas apart, giving regularity to the arrays. These results support the hypothesis that the regularity observed in arrays of astrocytes in intact tissue results from an interaction among astrocytes, independent of neighbouring structures, and lead us to suggest that the cell-cell interactions involved in contact spacing serve to distribute astrocytes through the central nervous system, and may, in other tissues, underlie the formation of epithelia.

Animals↗