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Biomedical subjects

K Williams

Publications and source records attributed to K Williams.

At least 307 records · Page 17Linked to original sources
PubMed1994

Transcranial assessment of maternal cerebral blood flow velocity in normal VS pre-eclamptic women (variation with maternal posture). A preliminary study.

To compare the effect of a change in maternal posture on maternal cerebral blood flow velocity assessed transcranially in a normal vs a pre-eclamptic group 5 normotensive and 5 pre-eclamptic patients had maternal middle cerebral artery (MCA) blood flow velocity assessed in 2 positions supine and sitting upright using a 2 mHz transcranial doppler ultrasound. Comparison was then made of the effect of a change in posture on cerebral blood flow velocity in both groups using paired student-t test. Normotensive women showed minimal change in MCA blood flow velocity while pre-eclamptic women showed a 20% rise in all aspects of MCA blood flow velocity from supine to sitting. In pre-eclamptic patients MCA blood flow velocity which showed a significant rise with change in posture is not accompanied by significant changes in blood pressure and so is not a secondary response to a change in cardiac output by may be a primary effect related to local circulatory changes. Transcranial assessment of maternal cerebral blood flow velocity performed in normotensive and various hypertensive groups showed significant variation with change in posture in the pre-eclamptic group.

Blood Flow Velocity↗
PubMed1994

The expression of CD59 in normal human nervous tissue.

The expression of CD59, a complement regulator of the formation and function of the terminal cytolytic membrane attack complex, was studied in human normal nervous tissue by immunohistochemical markers using two monoclonal antibodies 1F5 and MEM43. CD59 was present on Schwann cells, neurons and endothelial cells in the peripheral nervous system (PNS), and on Schwann cells in culture. In the central nervous system (CNS) CD59 was found predominantly on endothelial cells. There was also a diffuse staining of white and grey matter of the spinal cord and brain, presumably of microglia, oligodendrocytes, astrocytes and neurons, as these cells were CD59 positive in culture. Furthermore, CD59 was detected in the cerebrospinal fluid (CSF) of healthy individuals. CD59 in the PNS and CNS was glycosyl-phosphatidylinositol linked and had a molecular weight of 19,000-25,000. The presence of CD59 on various cells of the nervous system and in the CSF suggests that regulation of complement activation by this protein is important in neural host defence mechanisms.

Adult↗
PubMed1994

Transcranial assessment of maternal cerebral blood flow velocity in normal vs. hypertensive states. Variations with maternal posture.

This study compared the effect of a change in maternal posture on maternal cerebral blood flow velocity assessed transcranially in normal vs. various hypertensive groups. Ten normotensive, 10 preeclamptic and 10 chronically hypertensive patients had maternal middle cerebral artery (MCA) blood flow velocity assessed in three positions--left lateral decubitus, supine and sitting upright--using 2-mHz transcranial Doppler ultrasound. Comparison was then made of the effect of a change in posture on cerebral blood flow velocity in each group using analysis of variance with Student's t test for statistical significance. Normotensive and chronically hypertensive women showed minimal changes in MCA blood flow velocity, while preeclamptic women showed a 30% rise in all aspects of MCA blood flow velocity from the left lateral decubitus to sitting up. In preeclamptic women, MCA blood flow velocity, which showed a significant rise with changes in posture, was not accompanied by significant changes in blood pressure and so is not a secondary response to a change in cardiac output but may be a primary effect of local circulatory changes.

Adult↗
PubMed1994

HLA class II molecules (HLA-DR, -DP, -DQ) on cells in the human CNS studied in situ and in vitro.

Human leucocyte antigen (HLA) class II molecules expressed by antigen-presenting cells (APC) are major restriction elements in the interaction between APC and T cells of the CD4+ subtype. To explore the immune accessory function of cells in the central nervous system (CNS), we studied the expression of HLA-DR, -DP, and -DQ molecules on CNS cells in situ and in vitro. Reactive microglia and perivascular cells in multiple sclerosis lesions expressed all three HLA class II molecules, whereas microglia in the normal CNS expressed HLA-DR only. All three HLA class II molecules were up-regulated on cultured microglia after stimulation with interferon-gamma (IFN-gamma). Microglial stimulation of allogeneic CD4+ T cells in a mixed lymphocyte reaction (MLR) was effectively blocked using anti-HLA-DR monoclonal antibodies (mAb) but not using anti-HLA-DQ mAb. HLA class II-positive astrocytes and endothelial cells were not identified in normal or diseased CNS. Cultured astrocytes stimulated with IFN-gamma could, however, be induced to express HLA class II antigens of all subtypes, although great variability was observed between different donors. Our results indicate that although both microglia and astrocytes are capable of expressing all HLA class II subtypes in vitro, subtype expression differs between normal and pathological states in situ. Such selective expression may be associated with functional properties.

Adult↗
PubMed1994

Maternal middle cerebral artery blood flow velocity variation with gestational age.

OBJECTIVE: To assess the variation of the maternal middle cerebral artery blood flow velocity with gestational age in a normotensive pregnant population. METHODS: Middle cerebral artery blood flow velocity was assessed transcranially in 154 normotensive pregnant women using a 2-MHz pulsed probe. We assessed maximum systolic, minimum diastolic, and mean velocity and resistance index. Subjects were classified into seven gestational age categories of 4-week intervals starting from 13 weeks. Analysis of variance was used to indicate a significant difference in cerebral blood flow velocity with gestational age, and Tukey test to assess the significance. RESULTS: Maximum systolic velocity fell significantly in the third trimester (P < .01) to the lowest value (62 cm/second). Minimum diastolic velocity did not change with gestational age (28 cm/second). Mean velocity fell significantly from 25-36 weeks. CONCLUSIONS: Systolic and mean maternal middle cerebral artery blood flow velocity fell significantly with advancing gestational age, even though diastolic velocity did not vary. These changes did not correlate with mean arterial pressure changes with gestational age.

Blood Flow Velocity↗
PubMed1994

Subunit-specific potentiation of recombinant N-methyl-D-aspartate receptors by histamine.

Histamine has numerous functions in the brain and has recently been shown to modulate responses of N-methyl-D-aspartate (NMDA) receptors on hippocampal neurons by a mechanism that does not involve classical histamine receptors. In the present work, voltage-clamp recording was used to study the effects of histamine on recombinant NMDA receptors expressed in Xenopus oocytes, to determine whether histamine acts directly on NMDA receptors and to investigate the subunit specificity of the effects of histamine. Histamine potentiated responses to NMDA at heteromeric NR1/NR2 receptors containing splice variants of the NR1 subunit (NR1A or NR1E) that lack the amino-terminal insert, together with the NR2B subunit but not the NR2A or NR2C subunit. Stimulation by histamine (EC50 = 10 microM) had a novel profile, involving a rapid increase in the magnitude of NMDA-induced currents followed by slow (approximately 1-min) desensitization to a steady state level. Desensitization of the response to histamine was time dependent and could occur in the absence of receptor activation by NMDA. Stimulation by histamine was dependent on the concentration of agonist used to activate NR1A/NR2B receptors and was seen with high but not low concentrations of NMDA and glutamate. The effect of histamine was not blocked by classical histamine receptor antagonists but was mimicked by the histamine metabolite 1-methylhistamine. At a high concentration (1 microM) histamine produced a voltage-dependent inhibition of NMDA currents at NR1A/NR2B receptors and at receptors (NR1B/NR2B) that are not sensitive to stimulation by histamine. The results suggest that histamine acts directly at a novel recognition site on some subtypes of NMDA receptors to increase their activity.

Animals↗
PubMed1994

Mechanisms influencing stimulatory effects of spermine at recombinant N-methyl-D-aspartate receptors.

Stimulatory effects of spermine at heteromeric N-methyl-D-aspartate (NMDA) receptors expressed from cloned subunits were studied by voltage-clamp recording in Xenopus oocytes. At NR1A/NR2B receptors, in the presence of a saturating concentration of glycine, the magnitude of spermine stimulation was dependent on the concentration of NMDA or glutamate. In oocytes voltage-clamped at -25 mV, spermine markedly enhanced the response to 10 microM NMDA but had little or no effect on the response to 10 microM NMDA. This effect was not related to the size of the macroscopic currents, the quantity or ratio of injected receptor subunit RNAs, or a voltage-dependent block by spermine. Spermine induced a small (1.2-1.5-fold) decrease in the affinity of NR1A/NR2B receptors for NMDA and glutamate. This decrease was sufficient to counteract the stimulatory effect of spermine at low concentrations of NMDA and glutamate, resulting in no net effect of spermine or a decrease in macroscopic currents in the presence of spermine with low concentrations of agonist. Spermine did not alter the affinity of NR1A/NR2A receptors for NMDA. Endogenous polyamines could act as a bidirectional gain control at some native NMDA receptors containing the NR1A and NR2B subunits, by dampening the response to low concentrations of glutamate and enhancing the response to high concentrations of glutamate. Alternatively, polyamines could enhance the decay of NMDA receptor-mediated responses by increasing the rate of dissociation of glutamate from the receptor.

Animals↗
PubMed1994

Sensitivity of the N-methyl-D-aspartate receptor to polyamines is controlled by NR2 subunits.

The endogenous polyamine spermine has multiple effects on the N-methyl-D-aspartate (NMDA) receptor. These include an increase in the magnitude of NMDA-induced whole-cell currents that is seen in the presence of saturating concentrations of glycine ("glycine-independent" stimulation), an increase in the affinity of the receptor for glycine ("glycine-dependent" stimulation), and voltage-dependent inhibition. Although many of the properties of native NMDA receptors are seen with homomeric NR1 receptors expressed in Xenopus oocytes, we have found that the effects of spermine are differentially regulated by NR2 subunits in heteromeric NR1/NR2 receptors. Glycine-independent stimulation by spermine occurred at homomeric NR1A receptors, which lack the amino-terminal insert in NR1, and at heteromeric NR1A/NR2B receptors but not at heteromeric NR1A/NR2A or NR1A/NR2C receptors. Glycine-independent stimulation was not seen at homomeric NR1B receptors, which include the amino-terminal insert in NR1, or at heteromeric receptors containing NR1B. Thus, glycine-independent stimulation by polyamines requires the presence of an NR1 variant, such as NR1A, that lacks the amino-terminal insert, but the manifestation of the stimulatory effect is controlled by the type of NR2 subunit present in a heteromeric complex. Glycine-dependent stimulation was seen at NR1A/NR2A and NR1A/NR2B receptors and may therefore involve a second polyamine binding site distinct from that which produces glycine-independent stimulation. The voltage-dependent inhibitory effect of spermine, which is more pronounced at hyperpolarized membrane potentials, occurred with similar magnitudes at NR1A/NR2A and NR1A/NR2B receptors but was absent at NR1A/NR2C receptors. Thus, NR2 subunits control both the stimulatory and inhibitory effects of spermine at NMDA receptors. Stimulation but not inhibition by spermine was seen at NR1A/NR2B receptors in the presence of extracellular Mg2+. Stimulation, seen in the presence of physiological concentrations of Ca2+ and Mg2+, may be the predominant effect of polyamines at NMDA receptors in the intact nervous system.

Animals↗
PubMed1994

Expression of mRNAs encoding subunits of the N-methyl-D-aspartate receptor in cultured cortical neurons.

The expression of mRNAs encoding subunits of the N-methyl-D-aspartate (NMDA) receptor was examined in cortical neurons maintained in primary culture. Cultures were prepared from embryonic day 17 rat neocortex. At this developmental age, levels of NR1, NR2A, NR2B, and NR2C mRNA were low or undetectable. Expression of NR1 mRNA increased progressively between days 1 and 21 in vitro. The amount of NR2A mRNA did not change between days 1 and 7 but increased between days 7 and 21. In contrast, levels of NR2B mRNA increased between days 1 and 7, with little further change after day 7. The level of NR2B mRNA was approximately 4-fold higher than that of NR2A mRNA in 21-day cultures. Using ligand binding assays, the proportion of NMDA receptors having a low affinity for ifenprodil was also found to increase over time in culture. The increase in the expression of receptors having a low affinity for ifenprodil and the increase in NR1 and NR2A mRNAs were reduced or prevented by maintaining cells in medium with a low concentration of serum. The results are consistent with the hypothesis that inclusion of the NR2A subunit in native NMDA receptors is responsible for their low affinity for ifenprodil. Splice variants of NR1 lacking the 5' (amino-terminal) insert were found to be the predominant forms of NR1 in cultured neurons. Variants containing the 5' insert represented only a small (< or = 5%) fraction of total NR1 mRNA, and their proportion was not altered as a function of time in culture. Time-dependent changes in the properties of NMDA receptors and in the expression of subunit mRNA occurring in cultured neurons are similar to changes observed in developing rat brain. Thus, the developmental sequence of NMDA receptor expression that occurs in vivo is partially retained in neurons maintained in vitro.

Animals↗
PubMed1994

The effect of impurities on the stress distribution at the tooth/denture base resin interface.

The most common cause of teeth detaching from the denture base is the presence of impurities along the tooth denture-base interface. However detachment after a period of wear of the denture probably occurs due to the presence of stress concentrations along the interface from which cracks may initiate. The presence of the impurity will inevitably lower the stress threshold for cracks to propagate thereby increasing the risk of tooth detachment. Although this is obvious, there is no evidence to show the effect of impurities on the stress distribution at this interface. This pilot study utilised the finite element method to examine stresses at the tooth-denture base interface in the presence of simulated impurities interspersed along different positions on the interface. Within the limitations of the two-dimensional model used, it was concluded that the presence of an impurity at the edge of the palatal aspect of the interface has a significant effect on the stress magnitude. However, the presence of impurities elsewhere along the interface had no significant effect on the stress magnitude. This would have important implications during the processing of dentures.

Acrylic Resins↗
PubMed1993

Cloning of glycoprotein D cDNA, which encodes the major subunit of the Duffy blood group system and the receptor for the Plasmodium vivax malaria parasite.

cDNA clones encoding the major subunit of the Duffy blood group were isolated from a human bone marrow cDNA library using a PCR-amplified DNA fragment encoding an internal peptide sequence of glycoprotein D (gpD) protein. The open reading frame of the 1267-bp cDNA clone indicated that gpD protein was composed of 338 amino acids, predicting a M(r) of 35,733, which was the same as a deglycosylated gpD protein. Portions of the predicted amino acid sequence, matched with six CNBr/pepsin peptides obtained from affinity-purified gpD protein. In ELISA analysis, an anti-Duffy murine monoclonal antibody reacted with a synthetic peptide deduced from the cDNA clone. Hydropathy analysis suggested the presence of 9 membrane-spanning alpha-helices. In bone marrow RNA blot analysis, the gpD cDNA detected a 1.27-kb mRNA in Duffy-positive but not in Duffy-negative individuals. It also identified the same size mRNA in adult kidney, adult spleen, and fetal liver; in brain, it detected a prominent 8.5-kb and a minor 2.2-kb mRNA. In Southern blot analysis, gpD cDNA identified a single gene in Duffy-positive and -negative individuals. Duffy-negative individuals, therefore, have the gpD gene, but it is not expressed in bone marrow. The same or a similar gene is active in adult kidney, adult spleen, and fetal liver of Duffy-positive individuals. Whether this is true in Duffy-negative individuals remains to be demonstrated. A GenBank sequence search yielded a significant protein sequence homology to human and rabbit interleukin-8 receptors.

Amino Acid Sequence↗
PubMed1993

Induction of primary T cell responses by human glial cells.

Glial cells of the central nervous system (CNS) are postulated to function as immune accessory cells which may regulate immune reactivity occurring within the CNS, activating or alternatively inhibiting T cell responses. We have utilized surgically resected cerebral tissue derived from young adult humans to prepare dissociated cultures of glial cells (mixed astrocyte-microglia-oligodendrocyte cultures) and demonstrate that such cells are capable of acting as stimulators of primary T cell responses, using proliferation of T cells to allogeneic determinants on the glial cells as the test system. Studies of resected adult cerebral tissue indicated major histocompatibility complex (MHC) class II antigen expression on microglia in situ. Using a mixed lymphocyte reaction (MLR), we observed that enriched microglial cultures alone were capable of stimulating primary responses of freshly isolated T cells or the CD4+ T cell subset, a response which could be inhibited with an anti-MHC class II blocking antibody. In agreement with previous studies using rodent-derived astrocytes, we found that human astrocytes (fetal), could not initiate a primary T cell response even after up-regulation of MHC class II antigen expression with interferon gamma (IFN gamma) and tumor necrosis factor alpha (TNF alpha). Our results indicate that a primary T cell response, as well as a secondary response to a recall antigen, can occur within the CNS; our data implicate microglia as the central cell involved in the former.

Adolescent↗
PubMed1993

Intraobserver reliability of amniotic fluid volume estimation by two techniques: amniotic fluid index vs. maximum vertical pocket.

We evaluated the intraobserver agreement of two techniques of amniotic fluid assessment: amniotic fluid index and maximum vertical pocket. The intraobserver variation of the two forms of amniotic fluid assessment was obtained by evaluating amniotic fluid prior to fetal biometry (post-biometry value) and after fetal biometry (pre-biometry value). Between January and June 1990, this amniotic fluid assessment was by the maximum vertical pocket technique, and between July and December 1990, by the amniotic fluid index technique. In the Grace Maternity Hospital, Vancouver, 352 subjects were evaluated by the maximum vertical pocket technique, and 184 subjects by the amniotic fluid index technique.Amniotic fluid volumes were categorized into normal, oligohydramnios, and polyhydramnios, and the pre-biometry and post-biometry categories of amniotic fluid index and maximum vertical pocket techniques were compared by kappa statistics. The maximum vertical pocket technique showed poor intraobserver agreement (kappa = 0.33), but the amniotic fluid index technique showed good agreement (kappa = 0.72). With the poor reproducibility of the maximum vertical pocket technique in assessing extremes of amniotic fluid volume, it is difficult to support its use as a component of fetal assessment.

Journal Article↗
PubMed1993

The sensitivity and specificity of subjective and a semi-quantitative technique of amniotic fluid volume assessment in predicting intrapartum morbidity.

The aim of this study was to evaluate the ability of two techniques of amniotic fluid volume assessment to predict intrapartum morbidity in a high-risk population. A total of 213 pregnant women at the Grace Maternity Hospital, Vancouver, Canada were examined ultrasonically and the amniotic fluid volume was assessed subjectively and using the amniotic fluid index. Both techniques showed high specificity and negative predictive values for all outcome measures, but had an associated poor sensitivity and positive predictive value. Both techniques were similar in their ability to identify situations involving intrapartum morbidity. It is concluded that amniotic fluid assessment is a weak predictor of intrapartum morbidity but may be useful in certain conditions such as when the pregnancy is post-dates.

Journal Article↗
PubMed1993

Intestinal intraepithelial lymphocytes are activated and cytolytic but do not proliferate as well as other T cells in response to mitogenic signals.

Compared with T lymphocytes from other organs, intestinal intraepithelial lymphocytes (IEL) proliferate weakly in response to CD3/TCR ligation, and they do not respond at all to treatment with other mitogenic stimuli. These signals also failed to induce expression of the IL-2R alpha-chain on the surface of most IEL. IEL from germ-free mice, from V gamma 1.1-transgenic mice, and from beta 2-microglobulin-deficient mice also gave a weak proliferative response. Therefore, the low proliferative response is not linked to the level of exposure to gut bacterial flora, the V gamma region expressed by the TCR-gamma delta + IEL, or the presence of class I molecules that may be recognized by CD8+ IEL. The relatively small amount of proliferation in response to TCR signaling, therefore, is not likely to be the result of induction of anergy caused by previous contact with Ag. In contrast, ligation of the CD3/TCR complex could elicit a rapid cytotoxic response and serine esterase release by IEL. The unusual functional capabilities and the activation state of IEL are independent of the TCR isotype expressed by these cells. Freshly isolated IEL have a high intracellular microtubule-associated protein kinase-2 (MAP-2K) activity level, further suggesting that these cells are activated despite their weak proliferative response. Consistent with this, MAP-2K is tyrosine-phosphorylated in both untreated and PMA-treated IEL. In contrast, MAP-2K activation and tyrosine phosphorylation occur in other T cells only when they are activated by PMA or other treatments. MAP-2K activity also is elevated in IEL from germ-free mice, demonstrating that activation does not depend on normal levels of exposure to bacterial flora. The activation of protein kinases such as MAP-2K could reflect the differentiation state of IEL or Ag receptor stimulation of some of these cells by epithelial cells in the preparation.

Animals↗
PubMed1993

Developmental precise excision of Oxytricha trifallax telomere-bearing elements and formation of circles closed by a copy of the flanking target duplication.

The 4.1 kbp TBE1 elements of Oxytricha fallax and Oxytricha trifallax are deduced to transpose into a centrisymmetric target, CAnTG, and to duplicate the central AnT. Despite conserved C(A4C4)2 telomeric repeats at their tips, free TBE1s found during macronuclear development are not linear but 4.1 kbp circles closed on one copy of the AnT target duplication. The macronucleus-destined flanks are rejoined to regenerate the target, effecting efficient and precise somatic reversion of the germline transpositional mutation. A model is presented in which transposase catalyzes concerted precise rejoining of the flanks and cyclization of the excised element.

Animals↗