Search PubMed⌕ Search

Biomedical subjects

M J Williams

Publications and source records attributed to M J Williams.

At least 91 records · Page 5Linked to original sources
PubMed1995

Life support courses for all.

Many courses teaching advanced life support skills are now available in this country. These 'provider' courses include those dealing with cardiac, trauma and paediatric resuscitation. The numbers of applicants for all these courses far exceed the places available. There is further demand for places from those who currently hold advanced life support provider certificates and who require re-evaluation to maintain their certification. For many, particularly non-medical staff, obtaining funding or study leave to attend such a course may also be a problem. All these factors lead to delays in providing the training in advanced life support skills that is clearly needed. We here report on the development and success of local 1-day resuscitation courses as a means of introducing all staff who may be expected to cope with an emergency situation to the current principles of resuscitation. We do not suggest that such abbreviated courses are in any way a substitute for the full advanced life support course, but that they can provide tuition that may otherwise be unavailable.

Certification↗
PubMed1995

Performance, carcass yield, and carcass quality characteristics of steers finished on rhizoma peanut (Arachis glabrata)-tropical grass pasture or concentrate.

Steers (n = 156) finished on rhizoma peanut (Arachis glabrata Benth.)-tropical grass pasture in Florida and slaughtered at Central Packing, Center Hill were compared with steers (n = 152) finished on a concentrate diet in Texas and slaughtered at Excel, Plainview. Average daily gain during the growing and finishing periods was lower (P < .001) for forage-finished steers (.49 and .94 kg/d, respectively) than for concentrate-finished steers (.78 and 1.33 kg/d, respectively). Forage-finished steers had less fat over the ribeye (8.3 vs 11.4 mm; P < .01), lighter hot carcass weight (280 vs 346 kg; P < .001), and smaller longissimus muscle area (70.8 vs 86.6 cm2; P < .001) than concentrate-finished steers. Yield grade was not different (2.7 vs 2.6; P > .10), but quality grade was slightly better (low Select vs mid Select; P < .01) for concentrate-finished steers. Lean color of forage-finished steers was darker (P < .001) and fat of forage-finished steers had a creamier color (P < .001), but carcasses were not discounted due to yellow fat color. Shear force values were higher (6.8 vs 4.0 kg; P < .001) for forage-finished than for concentrate-finished steers. Off-flavors were detected by trained sensory panelists in 36% of forage-finished and 14% of concentrate-finished carcasses, but all at barely detectable levels. This research indicates that steers can be finished on rhizoma peanut-tropical grass pastures, but with some reduction in quality grade relative to concentrate-finished steers.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗
PubMed1995

Failure of imprinting at Igf-2: two models of mutation-selection balance.

The failure of maternal imprinting at the insulin-like growth factor II (Igf-2) locus predisposes individuals to several clinical conditions, including Wilms tumor. Having two functional Igf-2 genes, therefore, is selectively disadvantageous, and the condition is probably maintained in human populations by recurrent mutation. We propose two models that predict the expected frequency of functionally diploid individuals in a large population, in terms of a mutation rate, mu, and the selection coefficient against functionally diploid individuals, s. In the first model a mutant Igf-2 allele that cannot be imprinted arises from the standard, imprintable allele at a rate mu. Our second model hypothesizes a second modifier locus at which a recessive allele arises at rate mu. Mothers who are homozygous for this recessive modifier allele fail to imprint their eggs. Both models predict the expected frequency of affecteds to be 2 mu/s(1 + mu), approximately twice that predicted by the standard one-locus model of a recessive allele in mutation-selection balance. This frequency suggests that < or = 25% of the cases of Wilms tumor are due to the failure to imprint the maternal Igf-2 gene.

Diploidy↗
PubMed1994

Further characterization of the NH2-terminal fibrin-binding site on fibronectin.

The fibronectin (Fn) monomer contains two major sites of fibrin binding affinity present within the NH2-terminal and COOH-terminal domains; they consist of five (1F1-5F1) and three (10F1-12F1) consecutive type 1 modules, respectively. Recently, we have reported that the fourth and fifth type 1 module pair (4F1.5F1) of the NH2-terminal domain of fibronectin demonstrated fibrin binding ability (Williams, M. J., Phan, I., Harvery, T. S., Rostagno, A., Gold, L. I., and Campbell, I. D. (1994) J. Mol. Biol. 235, 1303-1311). In an attempt to further localize fibrin binding activity and to characterize the nature of the interaction between different type 1 modules of Fn and fibrin, we have tested a range of recombinant proteins and subtilisin generated proteolytic fragments of Fn in an enzyme-linked immunosorbent assay (ELISA) and by fibrin affinity chromatography. Of the recombinant proteins, we found that only the 4F1.5F1 exhibited significant fibrin binding activity, while 1F1, 1F1.2F1, 7F1, and 10F1 had little to no affinity for fibrin. On a molar basis, 4-5 times more 4F1.5F1 than a proteolytic fragment, corresponding to 1F1-5F1 (25.9 kDa) was required to cause 50% inhibition (IC50) of intact biotinylated Fn binding to fibrin in a competitive ELISA. This suggests that all five type 1 modules in tandem engender higher fibrin binding activity than the 4F1.5F1 alone. Furthermore, since fibrin binding activity of the intact Fn molecule was inhibited, by 70-80%, by the 4F1.5F1, the 25.9-kDa fragment, and a MoAb mapped to an epitope on the 4F1.5F1, the fibrin-binding site within the 4F1.5F1 contributes greatly to the non-covalent interaction of intact Fn with fibrin. These results provide significant insight into the Fn/fibrin interaction, a major component of the processes of wound repair and fibrin matrix assembly.

Amino Acid Sequence↗
PubMed1994

Characterization of the activation-associated isoform of CD43 on murine T lymphocytes.

A rat mAb termed 1B11 recognizes a 130-kDa cell surface glycoprotein expressed on T lymphocytes. Transfection studies using the Cd43 gene transfected into murine L cells, and immunoblots using anti-peptide Abs specific for the CD43 polypeptide identified the 1B11 Ag as the 130-kDa isoform of murine CD43. mAb 1B11 fails to recognize the other major CD43 isoform, 115-kDa CD43, either by Western blotting or by FACS analysis, thus differing from the previously characterized anti-CD43 mAb S7 that recognizes only the CD43 115-kDa isoform and not the CD43 130-kDa isoform. CD43 130-kDa recognized by mAb 1B11 is differentially expressed on T lymphocytes. Whereas most CD4-8-, CD4+8+, and CD4-8+ thymocytes express 130-kDa CD43 constitutively, the Ag is expressed by less than 20% of CD4+ T cells in immature and mature populations. On activation, expression of 130-kDa CD43 is up-regulated dramatically on CD4+ T lymphocytes, and to a lesser extent on CD8+ T lymphocytes. In contrast, T cell activation resulted in only minor up-regulation of 115-kDa CD43. CD43 130-kDa contains sialylated O-linked carbohydrate; however, recognition by mAb 1B11 is not dependent on the presence of sialic acid. Interestingly, removal of sialic acid by neuraminidase treatment of 1B11-negative CD4+ T lymphocytes or 1B11-negative EL4 cells confers 1B11 reactivity, suggesting that the 1B11 epitope is masked by sialic acid residues on the CD43 115-kDa isoform. The isoelectric point (pl) of 130-kDa CD43 was determined to be 6.0, which is higher than the pl reported for 115-kDa CD43. Different molecular properties of 115-kDa and 130-kDa CD43 and their differential expression in T cell subsets may indicate specific roles for these CD43 isoforms in T cell ontogeny and/or T cell function.

Animals↗
PubMed1994

Comparison of exercise echocardiography with an exercise score to diagnose coronary artery disease in women.

This study compares the accuracy of the routine exercise electrocardiogram, exercise score, and exercise echocardiography for the diagnosis of coronary artery disease (CAD) in women. Seventy women with a pretest probability of 53 +/- 30% for CAD were stressed using a maximal symptom-limited bicycle exercise protocol. Significant ST-segment change was defined by a depression of > 0.1 mV 0.06 second after the J point. The exercise score was calculated from ST response, heart rate, and workload using an equation derived from a multivariate model. A positive stress echocardiogram was defined by development of a new or worsening wall motion abnormality. The results were compared with the presence or absence of significant (> 50% diameter) stenoses at angiography. Exercise echocardiography identified 29 of the 33 patients (88%) with CAD, compared with 22 (67%) using ST analysis alone, and 20 (61%) using the exercise score (both p < 0.05 vs exercise echocardiography). The specificity of exercise echocardiography (84%) and the multivariate score (73%) were comparable, and exceeded that of the ST analysis (51%) in 37 patients without CAD (p < 0.01). The accuracy of exercise echocardiography (86%) exceeded that of the exercise score (67%, p = 0.01) and ST analysis (59%, p < 0.01). Among all 70 patients, an intermediate (20% to 80%) probability of coronary disease was identified in 21 patients on the basis of exercise echocardiography, in 38 based on the multivariate score, and in 38 based on the ST analysis alone. Exercise echocardiography is more sensitive than the exercise score, and more sensitive and specific than ST-segment analysis for the diagnosis of CAD in women.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Design and chemical synthesis of a neoprotein structural model for the cytoplasmic domain of a multisubunit cell-surface receptor: integrin alpha IIb beta 3 (platelet GPIIb-IIIa).

Integrins are a class of heterodimeric cell adhesion receptors involved in cell migration, cell anchorage, and cell-cell interactions. The cytoplasmic domains of integrins are of key importance in these activities. We have designed and chemically synthesized a 126 amino acid model protein (MP-1) containing both cytoplasmic tails of the platelet-derived integrin alpha IIb beta 3 covalently linked via a helical coiled coil. The coiled-coil tertiary structure was incorporated to mimic the membrane-spanning domain of the integrin and to act as a topological constraint fixing the two cytoplasmic tails in a parallel arrangement. This molecule, which contains two C-termini, was constructed by chemical dovetailing. The bromoacetylated and cysteinyl peptide synthons were unambiguously ligated through the formation of a thioether linkage. Ultraviolet circular dichroism (CD) spectroscopy has been performed on MP-1 and related compounds, confirming that a helical coiled coil is present within the MP-1 molecule. Significantly, the helicity apparently extends beyond the predicted amphiphilic region of MP-1. Fluorescence measurements suggest that a defined tertiary structure has formed by the association of the two cytoplasmic domains. We conclude that this is a practical design strategy for the study of the cytoplasmic domain of multisubunit cell-surface receptors.

Amino Acid Sequence↗
PubMed1994

Solution structure of a pair of fibronectin type 1 modules with fibrin binding activity.

The tertiary structure of the fourth and fifth type 1 module pair from the N terminus of human fibronectin, has been determined by two-dimensional homonuclear 1H nuclear magnetic resonance (NMR) spectroscopy. Comparison of each module fold with those of two other type 1 modules shows that the type 1 "consensus" structure is conserved in the pair. The modules connect end-to-end to form an elongated structure with a limited clockwise twist around the long axis, from N to C terminus. The short five residue linker sequence forms a tight loop and the relative orientation of the two modules is maintained by fixed and intimate hydrophobic contacts, dominated by a non-conserved tryptophan residue from the fourth type 1 module. The protein binds specifically to fibrin in an ELISA and surface accessible residues that may be involved in this and other protein interactions can be identified. The structure provides an insight into how chains of type 1 modules may link up in intact fibronectin.

Amino Acid Sequence↗
PubMed1994

Coronary artery ectasia: local pathology or diffuse disease?

It is not known whether general or local factors influence the pathogenesis of coronary ectasia. We analyzed prospectively coronary angiograms from 2,186 consecutive patients with 32 patients (1.5%), identified as having coronary artery ectasia. Sixteen subjects had coronary ectasia in more than one segment of the same or a different artery. In 20 of 72 (28%) ectatic segments there was a proximal, related stenosis. In these cases ectasia was more often saccular than fusiform (16 vs. 4) compared to ectasia without a proximal, related stenosis (21 vs. 31, P = 0.003), and the mean length of the ectatic segment was shorter (8.0 vs. 15.1 mm, P = 0.013). Subjects with ectasia after a stenosis often had other ectatic segments unrelated to stenoses. The high incidence of multisegment involvement suggests that coronary ectasia results from a diffuse abnormality of the vessel wall. In predisposed individuals localized ectasia may follow a stenosis, suggesting poststenotic dilatation.

Constriction, Pathologic↗
PubMed1994

A review of the management of a major incident involving predominantly paediatric casualties.

On 27 September 1993 a double-decker bus full of secondary school children was involved in a collision with a lorry. A total of 58 people were injured, including two fatalities. All except two of the casualties were children. Forty-two casualties, including all of the seriously injured, were taken to the Accident & Emergency Department at York District Hospital. Fifteen casualties were admitted, the majority with closed head injuries. Most of the injuries were of a minor nature, predominantly soft-tissue damage and superficial lacerations. This paper reviews these injuries and the implementation of the hospital major accident (MAJAX) plan. It identifies specific problems encountered with this incident. It also describes the measures taken retrospectively to upgrade the MAJAX plan. It highlights the difficulties encountered by medical staff called to the incident who were unfamiliar with managing injuries and describes retrospective attempts to improve the awareness of trauma management skills.

Accidents, Traffic↗
PubMed1994

The inner world of cell adhesion: integrin cytoplasmic domains.

Many of the interactions between cells and their environment are mediated by the integrin family of heterodimeric transmembrane receptors. The past decade has been a broad-based effort to decipher the rules by which integrins function. Integrins bind both intracellular and extracellular ligands and thus transfer signals across the membrane in both directions. The cytoplasmic domains of these receptors play a key role in this bidirectional flow of information and in the formation of direct physical linkages between protein structures on the inside and outside of the cell.

Journal Article↗
PubMed1994

Differential regulation of CD43 glycoforms on CD4+ and CD8+ T lymphocytes in graft-versus-host disease.

Two distinct T-cell glycoforms of CD43 result from differential glycosylation of a single gene product in vivo. The 115 kDa glycoform carries mainly tetrasaccharides and is a pan T-cell marker, whereas the 130 kDa glycoform carries mainly hexasaccharides and is associated with T-cell activation. CD43 has been shown to play a role both in enhancing and inhibiting cell adhesion; however, the function of the individual glycoforms is unknown. We have examined the distribution and regulation of the CD43 glycoforms in a murine model of acute graft-versus-host disease (GVHD) using monoclonal antibodies (mAbs) S7 and 1B11 specific for the 115 and 130 kDa CD43 glycoforms, respectively. An increase in T-lymphocyte CD43 130 kDa expression occurred during GVHD from day 4 onwards and coincided with splenomegaly and upregulation of the beta 1-6GlcNAc transferase (C2GnT), the key enzyme responsible for the addition of complex O-glycan branching to CD43. When T-lymphocyte subsets were examined for CD43 expression, we found that in GVHD, both CD43 glycoforms were upregulated on CD4+ T cells. However, in CD8+ T cells, CD43 115 kDa was downregulated while CD43 130 kDa was dramatically upregulated, such that two distinct CD8+1B11+ T-cell subsets were observed. These data demonstrate differential expression of the CD43 glycoforms in both resting and activated CD4+ and CD8+ T cells, and suggest that glycosylation differences between the CD43 glycoforms may reflect participation in the different functions of these T-cell subsets in immune disorders in vivo.

Acute Disease↗
PubMed1993

Activation of the medial septal area attenuates LTP of the lateral perforant path and enhances heterosynaptic LTD of the medial perforant path in aged rats.

Age-related memory impairments may be due to dysfunction of the septohippocampal system. The medial septal area (MSA) provides the major cholinergic projection to the hippocampus and is critical for memory. Knowledge of the neurobiological mechanisms by which the cholinergic system can attenuate age-related memory loss can facilitate the development of effective cognitive enhancers. At present, one of the best neurobiological models of memory formation is long-term potentiation/long-term depression (LTP/LTD). In previous studies, intraseptal infusion of the muscarinic agonist oxotremorine, which excites MSA neurons, improved memory in aged rats. The present study examined LTP and LTD in aged Fisher 344 rats following intraseptal infusion of oxotremorine. LTP and LTD were assessed using the slope of the EPSP recorded from the hilar region of the dentate gyrus. Induction of LTP was blocked in the lateral perforant path, but not in the medial perforant path, following intraseptal infusions of oxotremorine. The generation and amplitude of heterosynaptic LTD was enhanced in the medial perforant path, but not in the lateral perforant path. The results provide evidence that pharmacological activation of the MSA can modulate LTP and LTD in the hippocampus of aged rats. The implications of these results with respect to memory and synaptic plasticity in the hippocampus are discussed.

Aging↗
PubMed1993

Secondary structure of a pair of fibronectin type 1 modules by two-dimensional nuclear magnetic resonance.

The fourth and fifth type 1 module pair, corresponding to residues 151-244 from the amino terminus of human fibronectin, has been produced as a recombinant protein using a yeast expression system and studied by two-dimensional homonuclear 1H nuclear magnetic resonance (NMR) spectroscopy. The sequence-specific resonance assignment of the 1H NMR spectrum has been completed using a combination of 2D 1H nuclear Overhauser effect (NOE) spectroscopy, homonuclear Hartmann-Hahn, and correlated spectroscopy spectra recorded under a variety of pH and temperature conditions. Slow exchanging amide protons have been identified and estimates of many backbone 3JNH-C alpha H coupling constants were obtained by line shape fitting. The secondary structures of each module conform closely to the "consensus" fibronectin type 1 module structure determined previously for two other single type 1 modules. In the module pair described here, the two modules are linked by a short five-residue linker which appears to form a turn. The intermodule interface is defined by NOEs observed between a hydrophobic three-residue sequence from the fourth type 1 module and residues in the first double-stranded beta-sheet of the fifth type 1 module. The interaction is dominated by a tryptophan residue (unconserved in other type 1 sequences) within the fourth module, which causes large upfield ring current shifts for several proton resonances from the beta-sheet of the fifth module. The NMR data indicate that there is little or no relative reorientation of the two modules about the linker region but rather that the two modules combine with a fixed and intimate hydrophobic contact.

Amino Acid Sequence↗
PubMed1993

Nucleus basalis magnocellularis and attention: effects of muscimol infusions.

The basal forebrain is important in cognitive processing. Most studies have focused on the importance of this area in mnemonic processing. However, the nucleus basalis magnocellularis (NBM), which is a major component of the basal forebrain, may also be involved in attentional processes. Attention can influence the sensitivity of perceptual processes, as assessed by discriminability, or the selection of response strategies, as assessed by bias. This experiment examined whether temporary inactivation of the NBM, using the GABA agonist muscimol, would interfere with attention. Each rat was tested in a 2-choice reaction time (RT) task in which stimulus frequency was varied. RT and error rate increased, and discriminability decreased following muscimol infusions into the NBM. Bias was unchanged. The pattern of results provides evidence that the NBM is important in attention, and this influence of the NBM acts primarily on perceptual aspects of attention.

Animals↗