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Biomedical subjects

S J Lane

Publications and source records attributed to S J Lane.

At least 55 records · Page 3Linked to original sources
PubMed1994

Prediction of preschool sensory and motor performance by 18-month neurologic scores among children born prematurely.

OBJECTIVES: Premature birth places a child at risk for a number of academic and behavioral deficits. The challenge currently facing interventionists is to identify at an early age those preterm children who will develop such deficits. Identified children can then be targeted for intervention to forestall deficits at school age. METHOD: This study examined the use of a neurologic assessment, administered at 18 months of age, to identify children who will have difficulties at preschool age. Premature children identified as neurologically normal or neurologically suspicious at the age of 18 months were tested with the Miller Assessment for Preschoolers. RESULTS: Although there was some variability in performance, as a group the children classified as neurologically suspicious at 18 months continued to fall into a risk category at 4 years of age. CONCLUSION: Because such categorization may predict inadequate performance during the school-age years, monitoring of the child's development is warranted.

Brain Damage, Chronic↗
PubMed1994

Selective enhancement of GM-CSF, TNF-alpha, IL-1 beta and IL-8 production by monocytes and macrophages of asthmatic subjects.

Previous work has demonstrated an increase in the production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by monocytes derived from asthmatic individuals. We have suggested that monocytes and macrophages enhance airways inflammation by augmented cytokine production. We tested this hypothesis by measuring the production of GM-CSF and macrophage-derived cytokines, namely interleukin-1 beta (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8), from unstimulated and lipopolysaccharide (LPS)-stimulated peripheral blood monocytes and alveolar macrophages in 31 asthmatic and 11 normal, control subjects. The basal production of GM-CSF was four fold higher in the monocytes of asthmatic individuals, but there was no significant difference in the basal production of TNF-alpha, IL-1 beta and IL-8. After stimulation with LPS, asthmatic monocytes produced twofold more GM-CSF and fourfold more IL-1 beta than the monocytes from control subjects. Unstimulated macrophages from asthmatic subjects produced significantly less GM-CSF and TNF-alpha than macrophages from controls, and there was no difference in either IL-1 beta or IL-8 production. When stimulated by LPS, macrophages from asthmatic subjects produced twofold more GM-CSF, threefold more TNF-alpha and fourfold more IL-8. The levels of IL-8 produced by both monocytes and macrophages were at least 20 fold higher than those of the other cytokines measured. There is selectivity in the upregulation of cytokine production by monocytes and macrophages in asthma.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Startle modulation studies in autism.

We studied acoustic startle response and its modulation by prestimulation and by short-term and long-term habituation in 54 autistic patients and 72 normal age-matched controls. The startle response was measured as the amplitude and onset latency of the integrated orbicularis oculi EMG. There were no consistent significant differences between the autistic and control subjects in startle modulation by inhibitory or facilitatory prestimulation, short-term habituation of startle amplitude, long-term habituation of either startle amplitude or latency, or unmodulated startle amplitude. Differences between autistic and control subjects were limited to prolongation of unmodulated startle onset latencies in the autistics in all of the experimental paradigms (significant p = .005 only in the context of short-term habituation) and a statistically significant (p < .05) slower rate of short-term habituation of startle onset latency in the autistic patients, relative to the controls. Results provide only limited support for hypotheses of brainstem pathophysiology and no support for hypotheses of cerebellar pathophysiology in autism.

Acoustic Stimulation↗
PubMed1993

Differential in vitro regulation by glucocorticoids of monocyte-derived cytokine generation in glucocorticoid-resistant bronchial asthma.

We previously described a 3 kD neutrophil priming activity (NPA) derived from peripheral blood monocytes that is suppressed by glucocorticoid treatment of monocytes derived from individuals with corticosteroid-sensitive (CS) but not corticosteroid-resistant (CR) asthma. We compared the effects of glucocorticoids on the in vitro generation of other cytokines by monocytes of CS and CR asthmatic individuals. A total of 11 CS and 8 CR asthmatic subjects were studied. Monocytes were cultured overnight in the presence or absence of 5 micrograms/ml of lipopolysaccharide (LPS) with or without hydrocortisone (HC) or dexamethasone. TNF-alpha, IL-1 beta, and GM-CSF were measured by ELISA, mRNA for these cytokines were detected by northern analysis, and NPA was identified by its capacity to enhance ionophore-induced LTB4 generation from neutrophils. In the absence of LPS there was no significant difference in the generation of cytokines between monocytes derived from CS and CR individuals. Treatment of monocytes by 10(-6) M HC suppressed NPA generation from CS (72%, p = 0.002) but not CR subjects (10%, p = 0.47). In contrast there was no effect of glucocorticoids on the generation of other cytokines from monocytes of either CS or CR subjects. In the absence of LPS, mRNA for IL-1 beta and GM-CSF were not detected by northern analysis, and glucocorticoids had no significant effects on mRNA for TNF-alpha in either group. LPS at 5 micrograms/ml enhanced cytokine but not NPA generation and markedly increased cytokine mRNA in monocytes of both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Detection of GM-CSF in asthmatic bronchial epithelium and decrease by inhaled corticosteroids.

The presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) in airway epithelial cells in vivo was assessed in 15 asthmatic and 9 normal subjects. GM-CSF was analyzed using immunohistochemistry with a polyclonal and a monoclonal antibody. Hue saturation intensity color image analysis was used to quantify staining. Asthmatic airway epithelial cells stained significantly more with anti-GM-CSF than those from normal subjects (p = 0.0013 and p = 0.0003 for the polyclonal and monoclonal antibodies, respectively). Additionally, 8 asthmatic individuals inhaled 1,000 micrograms beclomethasone diproprionate per day for 8 wk and 6 asthmatic patients inhaled matching placebo. There was a significant reduction of GM-CSF in the epithelium in the patients who were given corticosteroids (p = 0.014), whereas the group of subjects who were given placebo showed no significant change in GM-CSF staining. There was a correlation between the percentage suppression of GM-CSF staining by inhaled corticosteroids and the percentage increase in FEV1 (r = 0.61, p < 0.05) and percentage decrease in carbachol responsiveness (r = 0.80, p < 0.01). These findings suggest that GM-CSF may play a role in the inflammatory processes of bronchial asthma and that the epithelial cell may be a target cell for drug action.

Administration, Inhalation↗
PubMed1993

Limitations of corticosteroid effects in asthma: biochemical approach.

Glucocorticosteroids (GCS) are the most effective treatment for bronchial asthma. Their mechanism of action, however, remains unknown, and a small proportion of asthmatic sufferers do not respond to their effects. GCS resistance in bronchial asthma may be secondary to altered bioavailability, a consistent polymorphism in the glucocorticoid receptor (GR), defective interaction with other transcription factors and/or deoxyribonucleic acid (DNA), or to a specific gene defect. Corticosteroid resistant bronchial asthma (CR asthma) cannot be explained on the basis of altered pharmacokinetics, or defective nuclear translocation or ligand binding of the GR, in CR subjects. Furthermore, peripheral blood monocytes (PBM) derived from asthmatic subjects generate a 3 Kd activity, which is proinflammatory in vitro for neutrophils and which is selectively inhibited by GCS in corticosteroid sensitive (CS) asthmatic subjects, with no inhibition seen in the CR group, suggesting a specific gene(s) defect.

Asthma↗
PubMed1992

The squalestatins, novel inhibitors of squalene synthase produced by a species of Phoma. II. Structure elucidation.

Three novel fungal metabolites 1-3 isolated from cultures of a Phoma sp. C2932, are potent and selective inhibitors of squalene synthase. Their structures have been determined by a combination of spectroscopic, X-ray crystallographic and chemical methods; these natural products incorporate the highly functionalised bicyclic core, [1S-(1 alpha, 3 alpha, 4 beta, 5 alpha, 6 alpha, 7 beta]-4,6,7-trihydroxy- 2,8-dioxabicyclo-[3.2.1]octane-3,4,5-tricarboxylic acid.

Antifungal Agents↗
PubMed1991

Modulatory influence of continuous tone, tone offset, and tone onset on the human acoustic startle response.

Startle modulation in young adult men, by continuous background tone and its offset, a 2-s sustained tone and its offset, and the onset of a 25-ms tone pip were compared. Tone (75dB 1000 Hz) offset and onset occurred either 2000 ms or 100-120 ms before the startle stimuli (104dB (SPL), 50-ms white noise bursts). Blink amplitude and latency were unaffected by continuous background tone. Blink amplitude was reliably inhibited by 100-ms offset of both the continuous background tone and the 2-s sustained tone or 120-ms onset of the tone pip, whereas effects on latency were more variable. Facilitation of blink amplitude and latency was significant but weak and only following the 2-s sustained tone, and only with respect to one of two experimental contexts. These findings support those of others and suggest that startle inhibition results from activation of neurons responding to transient environmental changes. The degree of inhibition appears to be related to stimulus value. Startle amplitude facilitation following long sustained prestimulation intervals is dependent on experimental context. Overall latency and amplitude modulation tend to be concordant, leading to the conclusion that the mechanism(s) underlying both are context dependent and linked in the adult human.

Acoustic Stimulation↗
PubMed1991

Effects of corticosteroids on cytokine generation and expression of activation antigens by monocytes in bronchial asthma.

The capacity of corticosteroids to inhibit the secretion of cytokines and the expression of selective antigens on monocytes has been studied in corticosteroid-sensitive (CS) and corticosteroid-resistant (CR) asthmatic patients. Incubation of monocytes derived from CS subjects with hydrocortisone inhibited the production of the enhancing activity, whereas in CR subjects hydrocortisone at concentrations of up to 10(-4) M did not suppress the release of enhancing activity. There was a rank order of potency for corticosteroid action: hydrocortisone less than methylprednisolone less than dexamethasone. The major activity was characterized as a heat-sensitive peptide of 3,000 daltons. The expression of CR1, CR3 and class II on asthmatic peripheral-blood mononuclear cells was increased relative to normal control donors. Culturing monocytes for 24 h in the presence of 10(-4) M hydrocortisone inhibited the expression of CR1, CR3 and class II in CS subjects but not in CR individuals. These results suggest that monocytes of CR asthmatic patients can increase the inflammatory potential of neutrophils and that they are hyperactive, as indicated by increased cytokine production and enhanced expression of activation markers, despite the presence of corticosteroids.

Adrenal Cortex Hormones↗
PubMed1991

Glucocorticoid receptor characteristics in monocytes of patients with corticosteroid-resistant bronchial asthma.

The mechanism of corticosteroid resistance in bronchial asthma has been studied by determining the rank order of potency for different corticosteroids in inhibiting the generation of a 3 kD molecule from peripheral blood monocytes isolated from corticosteroid-sensitive (CS) and corticosteroid-resistant (CR) asthmatic subjects, which augments leukotriene B4 (LTB4) generation by human neutrophils (PMN) stimulated by calcium ionophore. In addition, binding studies with (3H) dexamethasone have been performed to determine the dissociation constant (Kd) and receptor numbers (Ro) in the monocytes of these two groups of subjects. The concentration of corticosteroid producing 50% inhibition (IC50) was 600 nM, 70 nM, and 0.5 nM for hydrocortisone, methylprednisolone, and dexamethasone, respectively, in monocytes from CS individuals. There was only weak inhibition of the generation of enhancing activity by the corticosteroids in the CR asthmatic individuals. The dexamethasone Kd was 2.45 +/- 0.58 nM (mean +/- SEM, n = 6) in the CS group and 1.6 +/- 0.35 nM (mean +/- SEM, n = 6) in the CR group of patients (p = 0.14). The Ro in the CS group was 3,605 +/- 984 binding sites per nucleus (mean +/- SEM, n = 6) and 4,757 +/- 692 binding sites per nucleus (mean +/- SEM, n = 6) in the CR group (p = 0.23). These findings indicate that corticosteroid resistance in bronchial asthma cannot be explained by abnormalities in corticosteroid receptor characteristics.

Adult↗
PubMed1990

Maturation of startle facilitation by sustained prestimulation.

The startle response to a 104dB (SPL) 50-ms burst of white noise was facilitated by prestimulation with a nonstartling tone sustained for 2 s prior to the startling stimulus in 3, 4, 5, and 8 year old children and young adults. Both startle amplitude and onset latency showed significantly greater facilitation in the preschool children than in the 8-year-olds and adults. The results of this experiment, which used a fixed prestimulation interval, were compared to those of an earlier study in which the prestimulation interval was varied. The maturational changes in startle facilitation in response to the 2-s prestimulation interval were similar in the two experiments. Hence the maturational effect on startle facilitation was independent of the uncertainty (as to when the startling stimulus would be given), which might be associated with variable prestimulation intervals. These findings suggest that the neuronal mechanisms that mediate startle facilitation undergo development during early childhood and mature about 8 years of age, and that this maturational sequence is relatively independent of attentional effects.

Acoustic Stimulation↗
PubMed1989

Extra-hypothalamic dopamine is not involved in the effects of hyperprolactinemia on male copulatory behavior.

Experiments were performed to determine if the inhibition of copulatory behavior observed in male rats with chronically elevated serum prolactin levels (hyperprolactinemia) is associated with changes in central dopaminergic function in the nigrostriatal and mesolimbic systems. Chronic hyperprolactinemia, induced by ectopic pituitary grafts, inhibited sexual activity but was not associated with changes in locomotor activity, serotyped behavior in response to various doses of apomorphine, or 3H-spiroperidol binding to striatal homogenates. However, open-field defecation was reduced in the pituitary grafted animals. The results of the present study show that changes in nigrostriatal dopamine receptor sensitivity do not contribute to the inhibition of sexual behavior in hyperprolactinemic male rats. In addition, these results also demonstrate that the effects of hyperprolactinemia are relatively specific to copulatory behavior and appear not to involve general behavioral suppression.

Animals↗
PubMed1988

The analysis of recombinant interleukin-2 by thermospray liquid chromatography-mass spectrometry.

The complete sequence of recombinant human interleukin-2 expressed in Escherichia coli has been confirmed by thermospray liquid chromatography-mass spectrometry (TS-LC-MS) of a tryptic digest derived from 100 micrograms (7 nmol) of reduced carboxymethylated interleukin-2. The preparation was shown by this method to contain predominantly unprocessed N-terminal initiator Met, with some authentic N-terminal Ala; the rest of the protein was as predicted from the DNA sequence, though some deamidated material was noted. TS-LC-MS proved to be a rapid and efficient method for surveying the protein tryptic peptide products allowing all the data to be collected in one chromatographic run; all tryptic fragments were identified by their molecular ions including those for the larger peptides (Mr 1500-3500) which, due to the presence of doubly and triply charged molecular ions, were brought within the mass range of the instrument (1800 Da). It is proposed that TS-LC-MS is a good general method for analyzing recombinant protein digests with respect to sequence confirmation, processing, and post-translational modification, and since each chromatographic peak is identified allows for subsequent monitoring of the protein by LC using uv detection. The method suffers from the disadvantages that all the sample is consumed during the experiment and that no fragment (sequence) ions are generally observed.

Amino Acid Sequence↗