PubMed Health⌕ Search

Biomedical subjects

D Nesbitt

Publications and source records attributed to D Nesbitt.

7 recordsLinked to original sources
PubMed2001

Inhibition of choroidal neovascularization by intravenous injection of adenoviral vectors expressing secretable endostatin.

Endostatin is a cleavage product of collagen XVIII that inhibits tumor angiogenesis and growth. Interferon alpha2a blocks tumor angiogenesis and causes regression of hemangiomas, but has no effect on choroidal neovascularization (CNV). Therefore, inhibitors of tumor angiogenesis do not necessarily inhibit ocular neovascularization. In this study, we used an intravenous injection of adenoviral vectors containing a sig-mEndo transgene consisting of murine immunoglobulin kappa-chain leader sequence coupled to sequence coding for murine endostatin to investigate the effect of high serum levels of endostatin on CNV in mice. Mice injected with a construct in which sig-mEndo expression was driven by the Rous sarcoma virus promoter had moderately high serum levels of endostatin and significantly smaller CNV lesions at sites of laser-induced rupture of Bruch's membrane than mice injected with null vector. Mice injected with a construct in which sig-mEndo was driven by the simian cytomegalovirus promoter had approximately 10-fold higher endostatin serum levels and had nearly complete prevention of CNV. There was a strong inverse correlation between endostatin serum level and area of CNV. This study provides proof of principle that gene therapy to increase levels of endostatin can prevent the development of CNV and may provide a new treatment for the leading cause of severe loss of vision in patients with age-related macular degeneration.

Adenoviridae↗
PubMed1996

Prolonged induction to delivery time in termination of pregnancy using 16, 16-dimethyl-PGE1-methyl ester (gemeprost) for fetuses with a neural tube defect or hydrocephalus.

A retrospective study is reported comparing the induction to delivery interval using gemeprost for termination of pregnancy, in the second trimester, in 3 groups of patients. It was observed that the mean induction to delivery interval was significantly longer in 75 pregnancies where there was a fetus with a neural tube defect and or hydrocephalus (31.7 hours) compared with 88 pregnancies with other fetal abnormalities (19.7 hours) and 84 pregnancies where there was an intrauterine death (11.3 hours). There was also an increase in the requirements for further intervention to obtain delivery in the group with a neural tube defect or hydrocephalus (n = 33) compared with where there was an intrauterine fetal death (n = 4) and other abnormality (n = 14). We believe these results should be considered when counselling patients who have requested termination of pregnancy for fetal abnormalities.

Abortifacient Agents, Nonsteroidal↗
PubMed1995

Cytoskeletal organization in clusters of isolated polarized skate hepatocytes: structural and functional evidence for microtubule-dependent transcytosis.

Isolated hepatocytes from the marine vertebrate Raja erinacea (the little skate) retain their structural and functional integrity as clusters of cells formed around a single tubular bile canaliculus, and therefore can be used as a model of polarized hepatocytes in situ. In this study we used confocal and conventional epifluorescence microscopy in conjunction with fluorescent markers and immunocytochemistry to examine the structure and function of the cytoskeleton in these cells. Actin filaments in the hepatocyte clusters were found cortically and also concentrated in a pericanalicular array, while microtubules appeared to radiate away from a concentration near the apical membrane of the biliary pole towards the basolateral sinusoidal surfaces. Treatment of clusters with the microtubule disrupting agent, nocodazole, resulted in the microtubules depolymerizing from the basolateral surfaces towards the apical surface, indicating that the microtubules were oriented with their plus ends at the basolateral surface and their minus ends at the apical surface. Nocodazole was also found to disrupt the ability of clusters to transcytose a fluorescent bile salt derivative into their canalicular lumens. We detected cytoplasmic dynein in skate hepatocyte homogenates by Western blotting using an anti-dynein intermediate chain antibody, and immunofluorescent staining of intact hepatocytes revealed a punctate vesicular pattern. The polarized arrangement of microtubules, the presence of cytoplasmic dynein, and the inhibition of bile salt secretion by nocodozole are consistent with the microtubule cytoskeleton playing a fundamental role in the mediation of transcytosis, endocytosis, and bile excretory function in these hepatocytes. These polarized isolated skate hepatocytes represent an excellent experimental model for the in vitro study of hepatic transport, and allow for important comparative studies aimed at elucidating the evolutionarily conserved nature of various hepatocyte structures amongst the vertebrates.

Actins↗
PubMed1992

Immunolocalization of kinesin in sea urchin coelomocytes. Association of kinesin with intracellular organelles.

We have recently used domain-specific monoclonal antibodies (mAbs) to immunofluorescently localize kinesin to vesicle-like structures in the cytoplasm of sea urchin coelomocytes. In order to characterize further these localization patterns we have examined the distribution of kinesin with respect to the arrangement of microtubules (MTs) and various organelles. In double-label experiments involving the immunofluorescent staining of kinesin (using a mixture of the mAbs SUK2, 4 and 5), MTs were labeled with an antiserum against sea urchin tubulin, the endoplasmic reticulum (ER) was labeled with an antiserum against a luminal calsequestrin-like protein, the Golgi apparatus was labeled with rhodamine-wheat germ agglutinin (WGA) or NBD-ceramide, mitochondria were labeled with rhodamine 123, endosomes were labeled with Texas Red-ovalbumin, and lysosomes were labeled with Lucifer yellow or acridine orange. Kinesin-labeled vesicle-like structures were found in the same regions of the cells as MTs and the ER, being widely distributed in motile cells, but restricted to the perinuclear regions of stationary cells. There also appeared to be a correlation between the distribution of endosomes and kinesin staining in a subpopulation of cells. The kinesin binding structures were found occasionally to align in linear arrays, consistent with the idea that kinesin may transport ER and endosomes along linear MT tracks. No clear correlations were observed between the kinesin staining and the distribution of mitochondria, the Golgi apparatus or lysosomes, suggesting that kinesin may specifically associate with only a subclass of organelles in coelomocytes.

Animals↗
PubMed1986

Medical Communication Behavior System. An interactional analysis system for medical interactions.

The study assessed the psychometric properties of the Medical Communication Behavior System. This observation system records time spent by the physicians and patients on specific behaviors in the categories of informational, relational, and negative situation behaviors by using hand-held electronic devices. The study included observations of 101 genetic counseling sessions and also assessed the outcome measures of patient knowledge and satisfaction. In addition, 41 of the sessions were rated using the Roter Interactional Analysis System, and 20 additional control subjects completed the post-counseling information without being observed to examine the effects of recording the session. Results showed good interobserver reliability, and evidence of concurrent, construct, and predictive validity. No differences were found between the observed and unobserved groups of any of the outcome measures.

Behavior↗
PubMed1976

Indomethacin induces rat uterine contractions in vitro and alters reactivity to calcium and acetylcholine.

The initial contractions of uteri in vitro from castrated, estrogen-treated rats, were markedly diminished following replacement with fresh bathing medium. Indomethacin and aspirin (10(-5) to 10(-4)M) strongly stimulated such quiescent preparations and reduced their subsequent responsiveness to Ca++. Reintroducing the initial bathing medium (which contained prostaglandin-like material), or adding prostaglandin F2alpha to the fresh medium, initiated uterine contractions and restored responsiveness to calcium ion. Injections of indomethacin into castrated, estrogen-treated rats reduced initial in vitro uterine motility, abolished production of prostaglandin-like compounds, and prevented either indomethacin, aspirin, or Ca++ from stimulating uterine contractions. Uterine responsiveness to acetylcholine in vitro was significantly reduced in rats pretreated with indomethacin.

Acetylcholine↗