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Biomedical subjects

A King

Publications and source records attributed to A King.

At least 289 records · Page 16Linked to original sources
PubMed1993

In situ hybridization and northern blot demonstration of HLA-G mRNA in human trophoblast populations by locus-specific oligonucleotide.

Trophoblast cells from normal first trimester pregnancies have been shown to express the nonclassical class I molecule, HLA-G, which is nonpolymorphic and has a heavy chain of 40 kD. In this study, in situ hybridization experiments were performed using a biotinylated HLA-G specific oligonucleotide on sections of normal placenta including the implantation site. HLA-G mRNA was identified in all extravillous trophoblast populations including the cytotrophoblast cell columns, interstitial trophoblast, endovascular trophoblast, and placental bed giant cells. In addition, villous cytotrophoblast and villous mesenchymal cells also contained HLA-G transcripts, but villous syncytiotrophoblast was always negative.

Blotting, Northern↗
PubMed1993

Expression of perforin, granzyme A and TIA-1 by human uterine CD56+ NK cells implies they are activated and capable of effector functions.

At the time the human placenta is established, the uterine mucosal lining (decidua) is infiltrated by abundant CD3- CD56bright natural killer (NK) cells. NK cells circulating in blood are known to contain perforin and granzyme A in their cytoplasmic granules. TIA-1, an RNA-binding protein capable of inducing DNA fragmentation, has also been found in the granules of cytolytic cells. In this paper, we demonstrate the presence of perforin, granzyme A and TIA-1 in the granules of uterine NK cells. Sixteen sections of non-pregnant endometrium throughout the menstrual cycle and six sections of early decidua, together with cytospins of four preparations of isolated decidual leukocytes were stained by both immunohistology and immuno-electron microscopy to localize perforin, granzyme A and TIA-1 to the cytoplasmic granules of CD56+ cells. The presence in vivo of these cytolytic molecules in a normal physiological situation implies that these uterine NK cells may have effector functions in the control of normal placentation.

Antigens, CD↗
PubMed1993

Expression of integrins by human trophoblast and differential adhesion to laminin or fibronectin.

The process of placental implantation involves a series of transformations of trophoblast from a single polarized epithelial layer resting on a basement membrane (villous trophoblast), to cellular aggregates (trophoblast columns) which ultimately disperse to invade uterine decidua as individual cells (interstitial trophoblast). Such tissue re-modelling is associated with changes in the constituents of the extracellular matrix and in the expression of matrix receptors by the cells, the most relevant being the family of integrins which bind to laminin and fibronectin. In this study we show, by immunohistology and flow cytometry, a gradual loss of laminin receptors with the concomitant acquisition of fibronectin receptors as trophoblast is transformed from the villous phenotype, through the cell columns, into the extravillous population. The pattern of staining for the alpha 5, alpha 6, beta 1 and beta 4 subunits indicates that the integrins expressed by trophoblast are predominantly the alpha 5 beta 1 and the alpha 6 beta 4 heterodimers. We have also shown that isolated trophoblast cells assume a flattened, sessile phenotype when cultured on laminin but exhibit a more spreading, motile morphology when plated on fibronectin. In addition, numerous multinucleated giant cells are observed on a fibronectin substrate. Our data suggest that the relative expression of laminin and fibronectin receptors may determine the morphology and behaviour of trophoblast during the process of implantation.

Cell Adhesion↗
PubMed1993

The scanning laser ophthalmoscope and retinal assessment in diabetes.

In order to evaluate the Scanning Laser Ophthalmoscope as a method of assessing diabetic retinopathy, 57 consecutive patients with diabetes were examined through undilated pupils using laser ophthalmoscopy followed by pupillary dilatation and direct ophthalmoscopy. Results of laser scanning were recorded on videotape and analysed independently. Scanning (both eyes) took under 5 minutes per patient. For the 113 eyes studied, the two techniques gave concordant results in 73/113 (65%). Where there was discordance, laser ophthalmoscopic severity was greater than direct ophthalmoscopy in 36/40 (90% of discordant results). In 4/40 eyes conventional ophthalmoscopic appearances were judged more severe than those seen with the laser. The laser ophthalmoscope may have value as a method of assessing diabetic retinopathy, but further work is required to evaluate its efficacy as a screening tool in patients with moderate to severe retinopathy.

Diabetic Retinopathy↗
PubMed1993

In vitro activity of MDL 62,879 (GE2270 A) against aerobic gram-positive and anaerobic bacteria.

The in vitro activity of MDL 62,879, a new peptide antibiotic that inhibits protein synthesis through an interaction with elongation factor Tu, against a wide range of recent clinical isolates of common aerobic gram-positive and anaerobic organisms was determined. MDL 62,879 was highly active against staphylococci (MIC for 90% of isolates [MIC90], 0.125 microgram/ml), streptococci (MIC90, 1 microgram/ml), and enterococci (MIC90, 0.03 microgram/ml). All isolates of peptostreptococci and Mobiluncus spp. were susceptible, as were most isolates of clostridia. MDL 62,879 was not active against isolates of fusobacteria or Bacteroides spp., but some isolates of Prevotella spp. and Porphyromonas asaccharolytica were susceptible.

Anti-Bacterial Agents↗
PubMed1993

Value of cerebrospinal fluid examination in the diagnosis of meningitis in the newborn.

Between 1 October 1988 and 30 September 1991 the results of all 896 cerebrospinal fluid examinations from 736 neonates were correlated with clinical diagnosis, treatment, and outcome. The prevalence of fungal or bacterial meningitis in babies requiring lumbar puncture was only 0.95%. Gram staining had a sensitivity of 68% and a positive predictive value of only 46% for the diagnosis of meningitis. Primary cultures directly onto agar plates had a sensitivity of 81% and positive predictive value of 46%. Broth enrichment cultures did not improve sensitivity and were frequently found to be false positive. Empirical treatment should not be altered unless more than a few organisms are seen on Gram staining. Primary cultures are adequate for the diagnosis of fungal and bacterial meningitis. Enrichment cultures should be performed only when the Gram stain and/or cell count suggests meningitis is likely. Clinicians should be aware that diagnostic tests performed in populations with a low prevalence of disease are likely to generate many false positive results and have a low positive predictive value.

Bacteriological Techniques↗
PubMed1993

The effect of leukemia inhibitory factor on bone in vivo.

The local effects of leukemia inhibitory factor (LIF) on bone turnover in vivo have been examined. Recombinant murine LIF (0.2 micrograms) or vehicle was injected daily for 5 days over the right hemicalvaria, and the mice were killed on day 6 or 13. Effects on calvarial bone morphology were assessed using quantitative histomorphometry of nondecalcified bone tissue. Increased bone resorption was present in LIF-treated hemicalvaria compared with that in the noninjected hemicalvaria or calvaria from mice injected with vehicle alone at both 6 and 13 days. Significant increases in LIF-treated animals were as follows. Eroded surface increased 10-fold (P = 0.022), osteoclast surface increased 5-fold (P = 0.003), osteoclast numbers increased 3-fold (P = 0.002), and the number of osteoclast nuclei increased 3-fold (P = 0.009). Fibrotic tissue was laid down in the resorption defects, and there was an accompanying thickening of the periosteum (3 times greater in LIF-injected animals; P = 0.003), causing the overall thickness of the treated bones to be almost doubled (P = 0.045). Indices of bone formation were increased in animals treated with LIF. Osteoblast numbers, osteoblast surface, and osteoid area were doubled (P = 0.012, 0.016, and 0.058, respectively). Similar effects of LIF were seen in indomethacin-treated animals. Small but statistically significant morphological changes were also seen in the left noninjected hemicalvariae when LIF-treated animals were compared to controls. LIF increased periosteal area (P = 0.01) and total mineralized bone area (P = 0.002). In conclusion, LIF accelerated bone turnover locally in a prostaglandin-independent manner in normal mice, demonstrating its potential to modify in vivo bone cell function dramatically.

Animals↗
PubMed1993

Expression of the colony stimulating factor-1 receptor (c-fms product) by cells at the human uteroplacental interface.

BACKGROUND: The hematopoietic growth factor colony-stimulating factor-1 (CSF-1) and its receptor (encoded by the proto-oncogene c-fms) are implicated in the regulation of human placental development. EXPERIMENTAL DESIGN: In this study, we have performed a detailed immunohistochemical localization of the CSF-1 receptor (CSF-1R) on cells of the uteroplacental interface in human first trimester pregnancy, supplemented by Northern blot, in situ hybridization, and flow cytometric analysis. CSF-1R expression by JEG-3 and JAR choriocarcinoma cells was also investigated. RESULTS: c-fms mRNA was detected in primary cultures of first trimester trophoblast and was localized to the extravillous cytotrophoblast columns streaming off the anchoring villi. CSF-1R was expressed by fetal Hofbauer cells in the mesenchyme of the chorionic villi, and this expression increased considerably from first trimester to term. No expression was seen on first trimester and term villous cytotrophoblast. CSF-1R expression on villous syncytiotrophoblast was absent at 6 weeks, strongest at 8-10 weeks, and faded by 12 weeks. First trimester extravillous cytotrophoblast columns were strongly and consistently positive for CSF-1R expression, as was the superficial shell of extravillous trophoblast over the maternal decidua. However, with deeper invasion and terminal differentiation into placental bed giant cells, this expression became weak or absent. Endovascular trophoblast was also only weakly positive for CSF-1R. At the implantation site itself, large numbers of decidual macrophages and CD3-, CD56bright large granular lymphocytes were seen. The macrophages expressed CSF-1R strongly, but large granular lymphocytes, decidual stromal cells, glandular epithelium, and endothelial cells were found to be negative for CSF-1R expression. No CSF-1R expression was detected in JAR choriocarcinoma cells, but CSF-1R was present in first trimester cultured trophoblast and JEG-3 choriocarcinoma cells, although this was shown to be intracellular. CONCLUSIONS: These results suggest that CSF-1 may regulate invasion and differentiation of human placental trophoblast, depending upon the spatial and temporal distribution of its receptor. CSF-1 may also influence placental development and function by acting via decidual and fetal macrophages, which are the other cell populations expressing the receptor.

Blotting, Northern↗
PubMed1992

Crystallization and preliminary X-ray analysis of three serotypes of foot-and-mouth disease virus.

Foot-and-mouth disease viruses from serotypes O, A and C have been crystallized. The particular strains studied include O1K, A10(61), A22 Iraq 24/64, A24 Cruzeiro and C-S8c1. In addition, crystals have been grown of G67, a monoclonal antibody neutralization escape mutant derived from O1K, and of virus R100, recovered after the establishment of a persistent infection in baby hamster kidney cells with C-S8c1. Empty particles, capsids which lack the RNA genome, have also been crystallized for subtypes A22 Iraq 24/64 and A10(61). In almost all cases, crystals suitable for high resolution structure determination were obtained from (NH4)2SO4 or mixtures of polyethylene glycol and NH4Cl.

Aphthovirus↗
PubMed1992

Agonist activity of sumatriptan and metergoline at the human 5-HT1D beta receptor: further evidence for a role of the 5-HT1D receptor in the action of sumatriptan.

We have recently cloned a novel human 5-HT1D receptor subtype termed 5-HT1D beta. CHO K1 cells expressing the human serotonin 5-HT1D beta receptor were assayed to determine the second messenger system of this receptor. Cyclic AMP radioimmunoassays revealed that the 5-HT1D beta receptor is negatively coupled to adenylate cyclase in this cell system. A maximum of 50% inhibition of forskolin stimulated cAMP production was obtained with 5-HT1 receptor agonists which was blocked by the non-selective 5-HT receptor antagonist methiothepin (pKB = 100 nM). The novel anti-migraine drug sumatriptan, a putative 5-HT1D selective compound, acted as an agonist at the 5-HT1D beta receptor. Most notably metergoline, a putative 5-HT1 receptor antagonist, did not block the effects of 5-HT and was found to be acting as a full agonist at the 5-HT1D beta receptor. The ability of metergoline to act as an agonist at the 5-HT1D beta receptor may explain why it does not inhibit 5-HT and sumatriptan induced contraction of dog saphenous vein and other large conducting arteries. These results suggest that the 5-HT1D beta receptor may be the site of action of sumatriptan in preventing migraine, and that metergoline's actions on the dog saphenous vein are not contradictory to that hypothesis, as previously reported.

Cells, Cultured↗
PubMed1992

Elevated arterial blood pressure in cardiac tamponade.

BACKGROUND: In cardiac tamponade cardiac output falls, but peripheral vascular resistance increases, so that systemic blood pressure may be maintained at normal or near-normal levels. We recently observed a patient with cardiac tamponade whose blood pressure was markedly elevated. METHODS: To determine the frequency of elevated blood pressure in patients with cardiac tamponade and their hemodynamic characteristics, we studied 18 consecutive patients with cardiac tamponade from a variety of causes using right heart catheterization. RESULTS: Six of the 18 patients had systolic arterial blood pressures ranging from 150 to 210 mm Hg (mean [+/- SD], 176 +/- 26) and diastolic pressures ranging from 100 to 130 mm Hg (mean, 113 +/- 14). All six had previously been hypertensive. After pericardiocentesis there was a significant decrease in blood pressure (to 139 +/- 13 mm Hg systolic, P less than 0.05; and 83 +/- 6 mm Hg diastolic, P less than 0.01) and peripheral vascular resistance (from 2150 +/- 588 to 1207 +/- 345 dyn.sec.cm-5, P less than 0.01). Cardiac output increased in all six. The other 12 patients, 3 of whom had a history of hypertension, had significant increases in cardiac output and systolic blood pressure (from 119 +/- 13 to 127 +/- 7 mm Hg, P less than 0.05) after pericardiocentesis, whereas peripheral vascular resistance decreased. Both groups had similar degrees of cardiac tamponade, as indicated by measurements of cardiac output and intrapericardial, right atrial, and pulmonary-artery wedge pressures. CONCLUSIONS: Elevated blood pressure may occur in some patients with cardiac tamponade who have preexisting hypertension. Moreover, blood pressure may fall after pericardiocentesis in patients who have elevated blood pressure associated with tamponade.

Adult↗