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Biomedical subjects

K Williams

Publications and source records attributed to K Williams.

At least 325 records · Page 18Linked to original sources
PubMed1993

Developmental switch in the expression of NMDA receptors occurs in vivo and in vitro.

The properties of many ligand-gated ion channels are altered during development. We have characterized a developmental switch in the sensitivity of NMDA receptors to the novel antagonist ifenprodil using ligand binding assays with rat brain membranes and voltage-clamp recording of Xenopus oocytes expressing NMDA receptors after injection of RNA from rat brain and from cloned subunits of the receptor. In neonatal rat brain, NMDA receptors have a uniformly high affinity for ifenprodil. During postnatal development, a second population of receptors having a 100-fold lower affinity for ifenprodil is expressed and represents 50% of NMDA receptors in adult rat brain. This developmental change also occurred in cortical neurons maintained in primary culture. Ifenprodil potently inhibited responses of homomeric NR1 and heteromeric NR1/NR2B receptors but not NR1/NR2A receptors expressed in oocytes, suggesting that inclusion of different NR2 subunits in native NMDA receptors can control the sensitivity to ifenprodil.

Animals↗
PubMed1993

Massachusetts emergency medicine closed malpractice claims: 1988-1990.

STUDY PURPOSE: To describe the characteristics of malpractice claims against emergency physicians and to identify causes and potential preventability of such claims. POPULATION: Malpractice claims closed in 1988, 1989, and 1990 against emergency physicians insured by the Massachusetts Joint Underwriters Association were compared with claims closed from 1980 to 1987 as investigated in our previous study. METHODS: Retrospective review of malpractice claim files by board-certified emergency physicians. RESULTS: The average indemnity and expense per claim were higher in the current study population than in our previous study population (P = .05). Claims in eight high-risk diagnostic areas (chest pain, abdominal pain, fractures, wounds, pediatric fever/meningitis, subarachnoid hemorrhage, aortic aneurysm, and epiglottitis) accounted for 50.8% of claims in this study and 55.5% of total monetary losses. Four claims in this study were related to two instances of failure of an emergency department radiograph follow-up system. The evaluation of patients who were intoxicated contributed to major monetary losses, especially in cases of fractures and head injury. CONCLUSION: Emergency physicians must have a particular awareness of their great risk exposure for missed myocardial infarction. Addition of dictation or voice-activated record generation systems, departmental protocols for radiograph follow-ups, and holding and re-evaluation of the intoxicated patient will help provide systems supports for reducing the liability of individual emergency physicians.

Costs and Cost Analysis↗
PubMed1993

Amniotic fluid assessment.

Amniotic fluid assessment is a tool for the evaluation of fetal well-being. Because of the uterine cavity being irregular direct evaluation is difficult and subsequently, indirect techniques have been utilized. The three ultrasound techniques currently used for the evaluation of amniotic fluid include 1) maximum vertical pocket, 2) subjective assessment, and 3) amniotic fluid index. A review of these techniques show that the amniotic fluid index technique is valid, and the subjective technique and the amniotic fluid index technique appear to have a good inter- and intraobserver variability. All three techniques have been shown to predict peripartum morbidity and mortality when they define decreased amniotic fluid. Amniotic fluid volume is a weak predictor of morbidity and should be used in conjunction with other fetal biophysical variables to predict perinatal outcome.

Amniotic Fluid↗
PubMed1993

Dentine hypersensitivity: the measurement in vitro of streaming potentials with fluid flow across dentine and hydroxyapatite.

Stimulus transmission across dentine, in conditions such as dentine hypersensitivity, is considered to occur via a hydrodynamic mechanism. This fluid flow in dentine may then induce a mechanoreceptor response in pulpal nerves. However, when fluid flows through a porous structure electrical potentials are also generated. The aim of this study was to develop a reproducible model system to measure streaming potential across dentine and hydroxyapatite and determine the influence of pressure. Using an acrylic cell, with silver electrodes, streaming potentials were recorded across dimensionally standardized dentine and hydroxyapatite specimens, over a pressure range of 1-6 atmospheres. Streaming potentials were found to be directly proportional to pressure and dependent on the electrical conductivity of the saline used in the cell. The results confirm the limited existing data on streaming potentials across dentine and indicate that at these low pressures excitation of pulpal nerves would not occur. However, if, as may be the case, stimuli applied to dentine create very high pressures, the resultant potentials generated could indeed evoke a neural response. The model system is worthy of further use to study this phenomenon and the factors which may influence it.

Dentin↗
PubMed1993

Development of the concept of middleness in children: response time and complexity.

24 boys and 16 girls ages 4 through 7 years were tested on an apparatus that required children to select the middle of 3, 5, 7, or 9 stimulus lights when arranged adjacent to one another and when spaced symmetrically or asymmetrically. Analysis indicated response time decreased with age and increased as a function of the number of stimulus lights in the task. Time to respond to asymmetrical arrangements was greater than for problems whose stimuli were arranged symmetrically.

Attention↗
PubMed1993

Effects of Agelenopsis aperta toxins on the N-methyl-D-aspartate receptor: polyamine-like and high-affinity antagonist actions.

The effects of synthetic alpha-agatoxins, corresponding to toxins found in the venom of the spider Agelenopsis aperta, on the N-methyl-D-aspartate (NMDA) receptor complex have been investigated by using ligand-binding assays with [3H]MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine] and electrophysiological studies of NMDA receptors expressed in Xenopus oocytes after injection of rat brain RNA. The alpha-agatoxins Agel-489 and Agel-505 (3-30 microM) enhanced the binding of [3H]MK-801 to NMDA receptors on membranes prepared from rat brain. The stimulatory effect of Agel-505 was attenuated by the polyamine antagonists diethylenetriamine and N-(3-aminopropyl)-1,10-diaminodecane. Higher concentrations of Agel-489 and Agel-505 inhibited the binding of [3H]MK-801. A related toxin, Argiotoxin-636, had inhibitory but not stimulatory effects on the binding of [3H]MK-801. In Xenopus oocytes voltage-clamped at -70 mV, Agel-505 inhibited responses to NMDA with an IC50 of 13 nM. This effect of Agel-505 occurred at concentrations approximately 10,000-fold lower than those that cause inhibition of [3H]MK-801 binding. Antagonism of NMDA-induced currents by Agel-505 in Xenopus oocytes was strongly voltage-dependent and may represent an open-channel blocking effect of the toxin, possibly due to an interaction at the Mg++ binding site. Although alpha-agatoxins can interact at the positive allosteric polyamine site on the NMDA receptor, stimulatory effects produced by this interaction may be masked in functional assays due to a separate action of the toxins as high-affinity, noncompetitive antagonists of the receptor.

Animals↗
PubMed1993

Responses to gram negative enteric bacterial antigens by synovial T cells from patients with juvenile chronic arthritis: recognition of heat shock protein HSP60.

OBJECTIVE: To investigate the antigenic specificity of synovial T cells in juvenile chronic arthritis (JCA). METHODS: Synovial fluid and peripheral blood mononuclear cells from 24 patients with JCA were tested for their proliferative responses to recall antigens, enteric organisms associated with reactive arthritis, influenza A and a recombinant preparation of a mycobacterial heat shock protein, HSP65. To investigate further recognition of this last antigen, synovial T cells from one B27+ patient with pauciarticular disease were cloned using HSP65. The specificity of the resultant clones was then examined. RESULTS: Marked synovial T cell responses to enteric organisms and to HSP65 were noted, particularly in HLA-B27+, pauciarticular patients; these were similar to those seen in a B27+ patient with reactive arthritis. Responses to enteric organisms and to HSP65 were significantly correlated, suggesting recognition of an epitope common to these antigen preparations. However, all of the T cell clones obtained using HSP65 proved to recognize E. coli derived antigens contaminating the recombinant HSP65 rather than the mycobacterial antigen; these contaminants included the 60 kDa E. coli HSP, GroEL. The GroEL specific T cells did not respond to heat shocked human cells; this suggests (but does not prove) that they do not crossreact with human HSP60. CONCLUSION: Synovial T cell recognition of antigens from enteric organisms associated with reactive arthritis is a common feature in pauciarticular JCA. Among the target antigens is the GroEL HSP, but T cells recognizing this antigen do not necessarily crossreact with the homologous human HSP60.

Antigens, Bacterial↗
PubMed1993

Ifenprodil discriminates subtypes of the N-methyl-D-aspartate receptor: selectivity and mechanisms at recombinant heteromeric receptors.

The effects of the atypical N-methyl-D-aspartate (NMDA) receptor antagonist ifenprodil were investigated by voltage-clamp recording of Xenopus oocytes expressing heteromeric NMDA receptors from cloned NR1 and NR2 subunit RNAs. In oocytes voltage-clamped at -70 mV, ifenprodil inhibited NMDA-induced currents at NR1A/NR2B receptors with high affinity (IC50 = 0.34 microM). The affinity of NR1A/NR2A receptors for ifenprodil (IC50 = 146 microM) was 400-fold lower than that of NR1A/NR2B receptors. The rate of onset of inhibition by low concentrations of ifenprodil acting at NR1A/NR2B receptors was considerably slower than the onset of inhibition seen with high concentrations of ifenprodil acting at NR1A/NR2A receptors. The onset and recovery of blockade by ifenprodil at NR1A/NR2B receptors were not activity dependent. The inhibitory effects of low concentrations of ifenprodil at NR1A/NR2B receptors were not voltage dependent. In contrast, the inhibitory effects of high concentrations of ifenprodil at NR1A/NR2A receptors were partially voltage dependent, and a greater inhibition of NMDA-induced currents was seen at hyperpolarized membrane potentials than at depolarized membrane potentials. The reversal potential of NMDA currents was not altered in the presence of ifenprodil. Ifenprodil may act as a weak open-channel blocker of NR1A/NR2A receptors. The degree of inhibition seen with 100 microM ifenprodil at NR1A/NR2A receptors was not altered by changes in the concentration of extracellular glycine. However, the inhibitory effect of 1 microM ifenprodil at NR1A/NR2B receptors was reduced by increasing the concentration of glycine. Thus, part of the mechanism of action of ifenprodil at NR1A/NR2B receptors may involve noncompetitive antagonism of the effects of glycine. These results indicate that the mechanism of action of ifenprodil, as well as the potency of this antagonist, is different at NR1A/NR2B and NR1A/NR2A receptors expressed in Xenopus oocytes.

Adrenergic alpha-Antagonists↗
PubMed1993

The tooth-denture base bond: stress analysis using the finite element method.

Although acrylic resin teeth are the most popular artificial teeth used for denture construction, a high number fracture away at the tooth-denture base interface. Various causes have been documented for this failure; however, it is logical that eventual fracture occurs due to localised tensile stresses at this interface. Examination of these stresses using the finite element method showed that on load application to the upper incisors, the maximum tensile stresses were concentrated within the body of the tooth and not at the tooth-denture base interface. Stresses encountered at the interface were relatively low and introduction of a crack made no significant difference to their magnitude.

Acrylic Resins↗
PubMed1993

Effect of captopril on changes in rats' hearts induced by long-term irradiation.

The aim of this study was to test the efficacy of captopril, an angiotensin-converting enzyme inhibitor and a known suppressor of fibrosis, in preventing late radiation-induced cardiac pathology. Myocardial functional, histochemical and ultrastructural-morphometric studies were done on perfused hearts of rats isolated 3 and 6 months after 60Co gamma irradiation with 20 Gy and age-matched controls. At each time the animals were divided into the following groups: nonirradiated controls; irradiated once with 20 Gy; irradiated as above and given daily doses of captopril; daily doses of captopril without irradiation. The results showed that captopril, while ameliorating the decrease in the indices of capillary function, increase in mast cells, fibrosis, number of atrial granules, and changes in nerve terminals, failed to prevent the progressive functional deterioration of the hearts after irradiation. These findings suggest that an intramyofiber derangement may be involved in the long-term myocardial complications of irradiation.

Animals↗
PubMed1992

Correlation of subjective assessment of amniotic fluid with amniotic fluid index.

We assessed the correlation between abnormal amniotic fluid volumes as defined by the two techniques of (1) subjective evaluation and (2) the amniotic fluid index. Ultrasound evaluation of amniotic fluid volume was conducted on 420 pregnant women with known gestational age greater than twenty weeks but less than 42 weeks. Amniotic fluid was evaluated subjectively and placed into one of three categories: normal, oligohydramnios or polyhydramnios. After fetal biometry was performed, the amniotic fluid volume was assessed semi-quantitatively by the amniotic fluid index technique and assigned to similar categories. We analyzed the data with 2 x 2 contingency tables, using amniotic fluid index as the 'gold standard test'. Our study demonstrates that there was moderate agreement (kappa.5) between both amniotic fluid techniques in the identification of oligohydramnios. However, agreement between the techniques was poor for the identification of polyhydramnios (kappa.16).

Amniotic Fluid↗
PubMed1992

Low temperature-induced fatty acid desaturation in Brassica napus: thermal lability of the process.

The leaves of Brassica napus plants grown at 5 degrees C have a higher rate of fatty acid desaturation in both the cytosolic and chloroplastic pathways of diacylglycerol biosynthesis than plants grown at higher (up to 30 degrees C) temperatures. This physiological response to low growth temperature results in higher levels of unsaturated fatty acids in the leaf membrane lipids. These data suggest that this low temperature-induced desaturation process is thermolabile and can be inactivated by placing the leaves at temperatures of 30 degrees C for 4-8 h. Our evidence suggests that it is an additional rapid process to the normal 'basal' desaturation which occurs at a relatively slower rate. The data also show that the C16 and C18 fatty acids in the cytosol are desaturated at different rates and react differently to the high temperature treatment, suggesting that they are separate processes and are controlled independently.

Brassica↗