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Biomedical subjects

M J Taylor

Publications and source records attributed to M J Taylor.

At least 19 recordsLinked to original sources
PubMed1992

Orientation of the valine-1 side chain of the gramicidin transmembrane channel and implications for channel functioning. A 2H NMR study.

The orientation of the valine-1 side chain of gramicidin was determined by solid-state 2H NMR using valine-1-deuterated (d8) gramicidin. The peptide was incorporated into DMPC bilayers that were oriented between glass plates. When the plates were oriented with their normal perpendicular to the magnetic field, four quadrupolar splittings were observed of 106, 68, 9.7, and 2.0 kHz. These resonances were assigned to C alpha D, C beta D, and the deuterons of each of the C gamma D3 methyl groups, respectively. The average orientation of the various C-D bonds was calculated with respect to the helix axis. The angle obtained for the C alpha-D resonance was consistent with a single-stranded beta 6.3-helical model for the backbone but not with double-helical models. The angles of the side chain were then fitted to a model for the right-handed beta 6.3-helix. Rotation of the valine-1 side chain yielded a set of torsion angles that matched the angles as determined from the 2H NMR measurements. The corresponding orientation of the valine-1 side chain (chi 1 = -5 degrees) was found to be quite unusual, but it explains well the importance of a branched side chain at position 1 for channel formation and stability. A van der Waals interaction between valine-1 of one monomer and alanine-5 of the other helps to stabilize the gramicidin dimer.

Amino Acid Sequence↗
PubMed1992

Molecular and channel-forming characteristics of gramicidin K's: a family of naturally occurring acylated gramicidins.

The gramicidin K family is a set of naturally occurring acylated linear peptides in which a fatty acid is esterified to the ethanolamine hydroxyl of either gramicidin A or C, and possibly also to gramicidin B (Koeppe, R. E., II, Paczkowski, J. A., & Whaley, W. L. (1985) Biochemistry 24, 2822-2826). These acylated gramicidins form membrane-spanning channels in planar lipid bilayers and therefore constitute a model system with which to study the structural and functional consequences of acylation on membrane proteins. This paper serves to characterize further the channels formed by acylated gramicidins A and C and to demonstrate that these channels are structurally equivalent to the channels formed by the standard gramicidins. We also present additional evidence for the ester linkage in the natural acylated gramicidins A and C and identify the fatty acyl chains.

Acylation↗
PubMed1992

An experimental study of the effect of mood on body size perception.

The study presented is an experimental investigation of the effect of mood on body size perception. Female students estimated their body size and indicated their degree of dissatisfaction with their body size before and after the induction of a negative or positive mood state. Compared with women who received the positive induced mood, the induction of low mood led to greater disturbances in body size perception in the form of a tendency to overestimate their body size more and significantly greater dissatisfaction with their body size. Furthermore, among the women who received the negative mood condition, compared with those with little or no concern with their body shape, for those with such concerns the induction of low mood led to greater disturbances in body size perception in the form of overestimating their body size significantly more and a tendency towards greater dissatisfaction with their body size. These findings suggest that depressed mood may play an important role in determining the extent of disturbance in body size perception in clinical populations.

Adult↗
PubMed1992

Inhibition of acute TCDD toxicity by treatment with anti-tumor necrosis factor antibody or dexamethasone.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) acute toxicity is characterized in part by a wasting syndrome with depletion of adipose tissue. Tumor necrosis factor (TNF) induces a similar response during chronic infection. The similarities of these toxic effects led to a hypothesis that TNF plays a role in TCDD acute toxicity. To test this hypothesis pharmacologic doses of an antibody specific for murine TNF and the potent anti-inflammatory agent Dexamethasone (DEX) were used to inhibit TCDD toxicity in mice. TNF antibody treatment resulted in a 54% reduction in TCDD-mediated mortality while DEX treatment, a glucocorticoid agonist that inhibits transcription of TNF, reduced mortality by 92%. Cyp 1A1 induction, the most commonly measured TCDD-mediated response, was not blocked by DEX, demonstrating separation of this biochemical effect from acute toxic responses to TCDD. These data suggest that TCDD-mediated changes in the TNF pathway may be an important mechanism for acute TCDD toxicity.

Animals↗
PubMed1992

Evidence that basal secretion of relaxin by individual cultured large luteal cells is influenced by mobilization of intracellular calcium: analysis by a reverse hemolytic plaque assay.

Ca2+ redistribution from an intracellular site(s) is a key biochemical event associated with relaxin (RLX) secretion by large luteal cells (LLCs) of porcine origin. However, the functional significance of internal stores of Ca2+ to basal rates of RLX secretion is not well understood. In addition, the identity of the intracellular storage site(s) for Ca2+ within LLCs is not known, nor is it clear if all RLX-releasing LLCs are equally dependent on this pool. In the present study, release of RLX from 24 h cultured luteal cells derived from early pregnant swine was monitored by a reverse hemolytic plaque assay (RHPA). Incubation of cultures in the presence of graded concentrations of thapsigargin (1 nM-1 microM), a plant sesquiterpene lactone that inhibits endoplasmic reticulum Ca(2+)-ATPase and thereby increases cytosolic Ca2+ concentrations, resulted in a dose-related increase in basal RLX secretion. The stimulatory effect of thapsigargin on RLX production was not abrogated by culture in Ca(2+)-free medium. Suppression of Ca2+ release from the endoplasmic reticulum of LLCs, achieved by incubating monolayers in medium containing dantrolene (1-100 microM), resulted in dose-related inhibition of basal RLX release. Taken together, these results suggest that the endoplasmic reticulum serves as a major storage site for Ca2+ redistribution within LLCs and, furthermore, that mobilization from this site is functionally coupled to basal secretion of RLX.

Animals↗
PubMed1992

Microleakage.

A critical review of techniques used in the assessment of microleakage in dental restorations is presented. These techniques include the use of air pressure, bacteria, radioisotopes, electrochemistry, chemical tracers and dye penetration. Wide variations in methodologies are revealed.

Dental Leakage↗
PubMed1992

Somatosensory evoked potentials and nerve conduction studies in patients with Guillain-Barré syndrome.

Somatosensory evoked potentials, F-waves, and nerve conduction studies (NCS) were performed to determine their usefulness in detecting electrophysiologic abnormalities in 23 children in the acute stage of Guillain-Barré syndrome. The studies were performed on average 8.3 days after the onset of neurological symptoms, before the period of maximal weakness. All patients had at least one abnormal test. Somatosensory evoked potentials (SEP) showed most abnormalities: 91% abnormal recordings with posterior tibial nerve (PTN) stimulation and 68% with median nerve (MN) stimulation. The nerve conduction velocities were abnormal in 76% and 67% with PTN and MN stimulation, respectively. The F-waves were abnormal in 66% (PTN) and 56% (MN). The SEP studies were helpful in detecting proximal and central conduction abnormalities in 26% of patients, and they were more sensitive in detecting an abnormality when compared with F-wave recordings. Furthermore, in one patient with normal NCS and F-waves the prolonged lumbar potential-P35 conduction time of the PTN-SEP was the only abnormality found. SEP can detect an abnormality and thus support the clinical diagnosis of Guillain-Barré syndrome in the acute stage when the results of more conventional tests are inconclusive.

Adolescent↗
PubMed1992

Host strain, H-2 genotype and immunocompetence do not affect the survival or development of Onchocerca lienalis infective larvae implanted within micropore chambers into mice or rats.

The survival, growth and development of Onchocerca lienalis 3rd-stage (L3) larvae implanted into mice within micropore chambers has been studied with a view to developing a vaccination model for studies of protective immunity in onchocerciasis. The influence of host genetics on worm recoveries and development (growth and moulting rate) was analysed in a panel of inbred mice (CBA, BALB/c, DBA/2, SJL, 129J, C57BL/10 (B10), C3H/He and NIH), together with mice of BALB and B10 backgrounds with different major histocompatibility complex (H-2) genes (BALB/c, BALB.K, BALB.B and B10, B10.D2/n, B10.BR, B10.S). Parasite recoveries and development were similar in all mouse genotypes tested. They were unaffected by procedures designed to block or modulate phagocytic cell function with carbon or carrageenan, or to suppress inflammation by treatment with hydrocortisone acetate. A comparison of chambers sealed with membranes designed to admit (5.0 microns pore size) or exclude (0.2 microns pore size) host cells demonstrated no effect on the percentage recovery of living larvae, although dead larvae were more frequently retrieved when cells were excluded. Recoveries and rates of development of larvae implanted into immunodeficient scid mice and athymic Hooded rats were similar to those recorded in immunocompetent controls. We conclude that host genetic factors and immunocompetence are not significant determinants of survival, growth or development of O. lienalis larvae implanted within micropore chambers into naive mice. Despite its limitations, the use of this system merits further investigation as an approach to the study of protective immunity against developing larvae in onchocerciasis.

Animals↗
PubMed1992

Visual evoked potentials in infants and children.

Visual evoked potential (VEP) studies are of great value in a wide variety of pediatric patients, including those with disorders of the sensory visual pathway and those at risk for visual pathway damage. VEPs are simple, non-invasive, and are particularly appropriate for infants and young children who cannot communicate visual symptoms or cooperate for standard vision assessment. VEPs in pediatric patients have the following main purposes: (1) detecting lesions causing dysfunction of the sensory visual pathways (the VEP is a sensitive indicator of subclinical lesions and can be used to differentiate visual impairment from visual inattention in young infants); (2) confirming functional loss when disorders of the visual system are present; (3) quantifying visual impairment in patients with known visual disorders, accomplished either empirically by noting the severity of the VEP abnormality to flash and pattern stimuli or by visual acuity estimation studies (early quantification of vision loss allows referral to early intervention programs, which can ameliorate the long-term consequences of the disability); (4) monitoring patients who are at risk for visual complications either from diseases (such as hydrocephalus or neurofibromatosis) or as a complication of therapeutic intervention (e.g., neurosurgery, chemotherapy) to help detect and avoid long-term sequelae of such therapies on the developing nervous system; (5) establishing prognosis for visual and systemic recovery based on flash VEPs for specific pediatric disorders including perinatal asphyxia in full-term neonates, acute-onset cortical blindness, and, to a fair extent, in comatose children; and (6) in some cases, contributing to the differential diagnosis. Abnormalities of flash and/or pattern VEPs are generally nonspecific to the type of exact location of the lesion, except in distinguishing prefrom postchiasmal lesions. However, in certain conditions, such as the hereditary ataxias of childhood, VEP abnormalities may help in the diagnosis. Similarly, deterioration in VEPs may help differentiate progressive from static encephalopathies. VEPs have become an indispensable tool in pediatric ophthalmology and neurology. They will probably play an increasingly important role in the future, primarily due to the difficulty in assessing visual system function in young or ill children and the VEP's sensitivity to subclinical damage in this aspect of the central nervous system.

Brain Damage, Chronic↗
PubMed1992

Prognostic reliability of somatosensory and visual evoked potentials of asphyxiated term infants.

The purpose of this study was to determine whether SEPs would improve the predictive power of VEPs for the prognosis of asphyxiated infants. 57 term infants had SEPs and VEPs recorded during the first three days of life, during the first week and at follow-up visits. All survivors have been followed for 18 to 24 months. 34 had a normal outcome, 12 had severe neurological sequelae and 11 died. The SEPs had both high sensitivity (96 per cent) and negative predictive power (97 per cent); normal SEPs virtually guaranteed normal outcome. The VEPs had both a specificity and positive predictive power of 100 per cent; abnormal VEPs guaranteed abnormal outcome. Both together had a higher predictive power than either alone. The combination of VEPs and SEPs yields a powerful means of prognostication for term asphyxiated infants; the results suggest that both be included in the assessment of this population.

Asphyxia Neonatorum↗
PubMed1992

Morphological evidence that activated polymorphs circulate in the peripheral blood of patients with rheumatoid arthritis.

Purified peripheral blood polymorphonuclear leucocytes (PMNs) from patients with rheumatoid arthritis (RA) have been found to differ from purified PMNs from normal subjects in ways that are consistent with their prior activation. However, it is currently contentious whether activated PMNs really circulate in patients with RA, or whether they are produced as an in vitro artefact of purification. Recently developed rapid leucocyte fixation and preparation technique showed that the proportion of polarised (activated) PMNs (36.9 (24.7)%, mean (SD); n = 31) was increased relative to that in control subjects (8.1 (5.6)%; n = 12). Serum cytidine deaminase levels, a biochemical marker of PMN lysis, were also increased in patients with RA (11.59 (7.26) U/ml) compared with those in controls (6.82 (3.78) U/ml), but the proportion of polarised PMNs and the levels of cytidine deaminase activity were unrelated to clinical assessments of inflammatory disease activity. Twelve patients who were not receiving drugs or who were receiving only non-steroidal anti-inflammatory drugs (NSAIDs) had more polarised PMNs than 19 patients receiving second line treatment in addition to NSAIDs (patients receiving NSAIDs, 49.6 (25.9)%; patients receiving second line treatment, 27.5 (21.1)%). Fluorescence activated cytometric analysis of CR1 and CR3 expression on PMNs from a randomly selected subgroup of patients with RA showed that the serum level of cytidine deaminase activity was correlated positively with the expression of CR1 (the C3b receptor) on the cell surface and that the proportion of polarised PMNs was positively correlated with the expression of CR3 (or CD11b/CD18), the iC3b receptor that is upregulated on activation. It is suggested that the polarised PMNs which circulate in blood samples from patients with RA represent cells which have been activated but not yet marginated, or activated cells which have marginated but subsequently returned to the circulating pool.

Adult↗
PubMed1992

Leucocyte integrin and CR1 expression on peripheral blood leucocytes of patients with rheumatoid arthritis.

Expression of the leucocyte integrins (CD11a, b, c/CD18) and of CD35 (CR1) on leucocytes from the peripheral blood of patients with rheumatoid arthritis (RA) (n = 14) and control subjects (n = 12) was measured by flow cytometry using a rapid fixation and leucocyte preparation procedure. The mean (SE) percentages of lymphocytes expressing CD11a (RA 93.4 (1.7)%; controls 97.2 (1.8)%) and CD18 (RA 91.3 (2.3)%; controls 97.0 (2.6)%) were lower and the percentage of monocytes expressing CD11b (RA 86.9 (11.4)%; controls 78.4 (11.9)%) and CR1 (RA 62.6 (15.5)%; controls 36.6 (17.6)%) were higher in patients with RA than in controls. In addition, the mean fluorescence intensity of CD18 (RA 22.1 (2.3); controls 30.7 (2.5)) on lymphocytes was decreased and that of CD11b (RA 4.5 (0.8); controls 2.9 (0.9)) and CR1 (RA 2.4 (0.4); controls 1.5 (0.5)) on monocytes was increased in patients with RA compared with controls. The functional importance (if any) of the altered expression of the antigens on lymphocytes is not yet known. Altered expression on monocytes is consistent with activation within the circulation.

Adult↗
PubMed1992

Basic fibroblast growth factor inhibits basal and stimulated relaxin secretion by cultured porcine luteal cells: analysis by reverse hemolytic plaque assay.

The role of the basic fibroblast growth factor (basic FGF) in the control of secretion of the ovarian protein hormone relaxin (RLX) by porcine large luteal cells (LLCs) was examined by use of a reverse hemolytic plaque assay. In this assay, luteal cells were cocultured in monolayers with protein-A-coupled sheep erythrocytes. In the presence of complement and porcine relaxin antiserum, a zone of hemolysis (a plaque) developed around a RLX-releasing LLC. The rate of plaque development in time-course experiments was used as an index of the rate of RLX secretion. Monolayers were bathed in medium containing graded concentrations of basic FGF in the presence or absence of a stimulatory secretagogue [0.01 microM prostaglandin E2 (PGE2)]. Exposure of luteal cell-containing monolayers to basic FGF resulted in a significant reduction (P less than 0.05) in the rate of RLX-induced plaque formation, evidence of an inhibitory effect of basic FGF on the rate of basal RLX secretion. This suppressive effect was variable in onset (1-3 h of incubation) and dose related. Minimally and maximally effective doses were about 10 and 30 ng/ml basic FGF, respectively. Higher doses of basic FGF (20 and 30 ng/ml) entirely suppressed RLX from a substantial subset of LLCs (10-20% of all LLCs), an indication of a differentially sensitive subpopulation. Addition of basic FGF (30 ng/ml) to monolayes also treated with PGE2 resulted in a significant (P less than 0.05) attenuation of the stimulatory effect of PGE2 on RLX secretion, evidence that these agents functionally interact in the modulation of RLX. We conclude that these results taken in association with the prior demonstration of the presence of basic FGF in luteal tissue suggest that basic FGF serves as a local inhibitory mechanism that regulates RLX secretion. Furthermore, the ability of basic FGF to counteract the effect of PGE2 implies that intraluteal stimulatory/inhibitory agents may act in concert to achieve fine control of RLX secretion. The observation of a preferentially responsive subpopulation is consistent with the possibility that basic FGF is implicated in heterogenous RLX secretion. Nevertheless, the physiological role(s) of basic FGF in the control of RLX secretion and the interrelationships of basic FGF with other local and systemic secretagogues remain to be clearly defined.

Animals↗
PubMed1992

Discordant secretion of relaxin by individual porcine large luteal cells: quantitative analysis by a reverse haemolytic plaque assay.

Individual large luteal cells (LLC) derived from pregnant swine differ conspicuously in their ability to secrete the peptide hormone relaxin under basal and stimulated conditions--the phenomenon of functional heterogeneity. The purpose of this study was to quantitate knowledge of this phenomenon through use of a reverse haemolytic plaque assay, a technique that utilizes antibody-directed, complement-mediated erythrocyte lysis to detect hormone secretion by single LLCs in culture. Measurement of individual plaque areas (an index of the amount of relaxin secreted) demonstrated an approximate 100-fold range in the amount of relaxin secreted by a single cell under basal conditions. This range was doubled by exposure to the phorbol ester, 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA; 50 nmol/l). Under basal conditions, 50 and 80% of the total amount of relaxin was secreted by approximately 10 and 30% of all LLCs respectively. The size of these fractions was not influenced by the time of incubation (1-8 h), or by the presence of either of two non-specific stimulatory relaxin secretagogues, PMA (50 nmol/l) or arachidonic acid (1 mumol/l). The unimodal frequency distribution of plaque areas (under basal or stimulated conditions) suggests that relaxin-secreting LLCs comprise a discrete functional population of secretory cells, at least under these experimental conditions. We conclude that a remarkably small fraction of LLCs secretes the majority of relaxin, and that the size of this fraction was not influenced by time or secretagogues.

Animals↗
PubMed1992

Transforming growth factor-beta is a potent inhibitor of basal and stimulated relaxin release by porcine luteal cells maintained in monolayer culture.

The effect of transforming growth factor-beta (TGF-beta) on relaxin release by porcine large luteal cells (LLC) was examined by use of a reverse haemolytic plaque assay. In this assay, mixed luteal cells were co-cultured in monolayers with protein A-coupled sheep erythrocytes. In the presence of complement and porcine relaxin antiserum, a zone of haemolysis (a plaque) developed around relaxin-releasing LLCs. The rate of plaque development in time-course experiments and the average size of plaque areas were used to monitor the rate of relaxin release and cumulative amounts of hormone respectively. Monolayers were bathed in medium containing TGF-beta alone, or in the co-presence of a stimulatory secretagogue (prostaglandin E2; PGE2). Exposure of luteal cell-containing monolayers to TGF-beta (1 ng/1-100 micrograms/1) elicited a dose-related inhibition in the rate of basal relaxin release. Minimal and maximal concentrations were approximately 10 ng/1 and 10 micrograms/1 respectively. Treatment with 1 microgram TGF-beta/1 reduced the cumulative amount of relaxin released to 63 +/- 6% of control values (mean +/- S.D., P < 0.05, n = 6; averaged over the whole course of the experimental incubation). Exposure of monolayers treated with TGF-beta to the relaxin-stimulatory secretagogue PGE2 (0.1 mumol) resulted in a significant (P < 0.05) increase in the amount of relaxin released by TGF-beta-suppressed LLCs, and restored rates of hormone release to control levels. This is evidence that TGF-beta and PGE2 interact antagonistically in the modulation of relaxin. The effect of TGF-beta was strictly time-dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Increased endotoxin sensitivity following T-2 toxin treatment is associated with increased absorption of endotoxin.

Oral exposure to T-2 Toxin (T-2) in experimental animals results in a syndrome similar to that observed in endotoxemia. Endotoxins are lipopolysaccharide, outer-membrane components of gram-negative bacteria which induce acute, inflammatory responses. In the present study, several aspects of endotoxin pathophysiology were investigated in mice following simultaneous exposure to T-2 and endotoxin, including mortality, hypothermia, tumor necrosis factor-alpha (TNF-alpha) and corticosterone production, and thymic weight. The disposition of endotoxin was also assessed, Acute, simultaneous exposure to T-2 (4 mg/kg, po) and endotoxin (3 micrograms/mouse, ip) resulted in increased mortality, hypothermia, TNF-alpha production, and thymic atrophy compared to treatment with either T-2 of endotoxin alone. Pretreatment of mice with endotoxin, a regime that renders the animals resistant to the effects of endotoxin, reduced many endotoxin effects in animals treated simultaneously with T-2 and endotoxin. Upon further investigation, it was observed that T-2 increased the absorption rate of endotoxin: as the peak height of serum endotoxin increased, the time-to-peak decreased, and the area under the curve was unchanged in animals treated simultaneously with T-2 and endotoxin. It was concluded that increased endotoxin absorption accounted for the increases in mortality, hypothermia, and TNF-alpha associated with T-2 exposure.

Animals↗