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1.  Feeding requirements of white sharks may be higher than originally thought 
Scientific Reports  2013;3:1471.
Quantifying the energy requirements of animals in nature is critical for understanding physiological, behavioural, and ecosystem ecology; however, for difficult-to-study species such as large sharks, prey intake rates are largely unknown. Here, we use metabolic rates derived from swimming speed estimates to suggest that feeding requirements of the world's largest predatory fish, the white shark (Carcharodon carcharias), are several times higher than previously proposed. Further, our estimates of feeding frequency identify a clear benefit in seasonal selection of pinniped colonies - a white shark foraging strategy seen across much of their range.
doi:10.1038/srep01471
PMCID: PMC3600591  PMID: 23503585
2.  The metabolic activity of gut microbiota in obese children is increased compared with normal-weight children and exhibits more exhaustive substrate utilization 
Nutrition & Diabetes  2011;1(7):e12-.
Objective:
The gut microbiota contribute otherwise impossible metabolic functions to the human host. Shifts in the relative proportions of gut microbial communities in adults have been correlated with intestinal disease and have been associated with obesity. The aim of this study was to elucidate differences in gut microbial compositions and metabolite concentrations of obese versus normal-weight children.
Materials and methods:
Fecal samples were obtained from obese (n=15; mean body mass index (BMI) s.d. score=1.95) and normal-weight (n=15; BMI s.d. score=−0.14) Swiss children aged 8–14 years. Composition and diversity of gut microbiota were analyzed by qPCR and temperature gradient gel electrophoresis (TGGE).
Results:
No significant quantitative differences in gut microbiota communities of obese and normal-weight children were identified. Microbial community profiling by TGGE revealed a high degree of both intra- and intergroup variation. Intergroup comparison of TGGE profiles failed to identify any distinct populations exclusive to either obese or normal-weight children. High-pressure liquid chromatography analysis identified significantly higher (P<0.05) concentrations of short-chain fatty acids (SCFA) butyrate and propionate in obese versus normal-weight children. Significantly lower concentrations of intermediate metabolites were detected in obese children, suggesting exhaustive substrate utilization by obese gut microbiota.
Conclusions:
Our results indicate that a dysbiosis may be involved in the etiology of childhood obesity. In turn, aberrant and overactive metabolic activity within the intestine could dictate survival or loss of individual microbial communities, leading to the altered population ratios previously identified in adult obesity.
doi:10.1038/nutd.2011.8
PMCID: PMC3302137  PMID: 23154580
obesity; pediatric; short-chain fatty acid; gut microbiota; metabolism
3.  Public health training in genitourinary medicine 
Sexually Transmitted Infections  2006;82(3):191-192.
GUM consultants need skills that fall into the broad area of public health
doi:10.1136/sti.2006.021345
PMCID: PMC2564736  PMID: 16731665
public health; genitourinary medicine; sexually transmitted infections; medical careers
4.  Strain rate imaging after dynamic stress provides objective evidence of persistent regional myocardial dysfunction in ischaemic myocardium: regional stunning identified? 
Heart  2005;91(2):152-160.
Objective: To investigate whether persistent ischaemic dysfunction of the myocardium after dynamic stress can be diagnosed from changes in ultrasonic strain rate and strain.
Design: Prospective observational study, with age matched controls.
Setting: University hospital.
Patients and methods: 26 patients (23 men, mean (SD) age 58.9 (8.1) years) with coronary artery disease but no infarction and 12 controls (9 men, aged 56.1 (8.8) years) with normal coronary arteriography and negative exercise test underwent treadmill exercise (Bruce protocol). Tissue Doppler echocardiography was performed at baseline, at peak exercise, and at intervals up to one hour. Systolic and diastolic velocity, strain, and strain rate were recorded in the basal anterior segment of 16 patients with proximal left anterior descending coronary artery disease.
Results: Patients developed ischaemia, since they experienced angina, exercised for less time, and reached a lower workload than the control group, and had ST segment depression (−2.4 mm). Myocardial systolic velocity immediately after exercise increased by 31% and strain rate fell by 25% compared with increases of 92% and 62%, respectively, in the control group (p < 0.05). During recovery, myocardial systolic velocity and strain rate normalised quickly, whereas systolic strain remained depressed at 30 and 60 minutes after exercise, by 21% and 23%, respectively, compared with baseline (p < 0.05 versus controls). Myocardial diastolic velocities and strain rate normalised but early diastolic strain remained depressed by 32% compared with controls for 60 minutes (p < 0.05). Strain during atrial contraction was abnormal for 30 minutes.
Conclusions: Myocardial strain shows regional post-ischaemic dysfunction in systole and diastole and may become a useful diagnostic tool in patients presenting with chest pain with a normal ECG.
doi:10.1136/hrt.2003.027490
PMCID: PMC1768711  PMID: 15657221
stunned myocardium; exercise; tissue Doppler echocardiography; strain rate imaging; Doppler myocardial imaging
5.  Incidence of embolism and paravalvar leak after St Jude Silzone valve implantation: experience from the Cardiff Embolic Risk Factor Study 
Heart  2003;89(9):1055-1061.
Background: Silver coating of the sewing ring (Silzone) was introduced as a modification of the St Jude Medical standard valve to provide antibacterial protection, but the valve has recently been withdrawn.
Objective: To study patients with these prostheses to assess possible adverse effects, and to guide their follow up.
Design: Prospective observational study of risk factors for stroke after valve replacement.
Setting: Cardiology and cardiac surgery departments in a tertiary centre.
Patients: There were 51 patients with Silzone and 116 with St Jude Medical standard valves. Patients undergoing aortic valve replacement were well matched for stroke risk factors. Silzone patients with mitral valve replacement were younger (mean (SD) age 61 (10) v 66 (7) years), more likely to be female (95% v 65%), and had more pulmonary arterial hypertension (100% v 78%), but fewer coronary artery bypass grafts (5% v 33%) than patients with standard mitral valve replacements (all p < 0.05).
Results: Follow up was 100% in the Silzone group (mean duration 3.0 (0.9) years) and 97.4% in the standard group (4.7 (1.4) years). Survival, morbidity, and anticoagulant control were documented over 682 follow up years (153 for Silzone and 529 for standard). There were six embolic strokes and one peripheral embolism in the Silzone group, all within three months after operation, and five embolic strokes and one peripheral embolism in the standard group. Freedom from major thromboembolism at three months was 65% in the Silzone mitral valve replacement group and 100% in the standard mitral valve replacement group (difference 35%, 95% confidence interval 8% to 62%). There was one reoperation for paravalvar leak in the standard group, but none in the Silzone group (NS). Anticoagulant control in the two groups was similar.
Conclusions: Patients with Silzone mitral valves had a high rate of early postoperative embolism but no excess paravalvar leak.
PMCID: PMC1767860  PMID: 12923026
valve prosthesis; Silzone valve; embolism; paravalvar leak
7.  Conduit arterial stiffness is associated with impaired left ventricular subendocardial function 
Heart  2003;89(4):449-450.
PMCID: PMC1769251  PMID: 12639882
conduit arterial stiffness; left ventricular subendocardial function
8.  Cost effectiveness of statins 
Heart  2000;83(6):713.
doi:10.1136/heart.83.6.713a
PMCID: PMC1760882  PMID: 10885942
9.  Cost effectiveness of HMG-CoA reductase inhibitor (statin) treatment related to the risk of coronary heart disease and cost of drug treatment 
Heart  1999;82(3):325-332.
OBJECTIVES—To estimate the cost effectiveness of statin treatment in preventing coronary heart disease (CHD) and to examine the effect of the CHD risk level targeted and the cost of statins on the cost effectiveness of treatment.
DESIGN—Cohort life table method using data from outcome trials.
MAIN OUTCOME MEASURES—The cost per life year gained for lifelong statin treatment at annual CHD event risks of 4.5% (secondary prevention) and 3.0%, 2.0%, and 1.5% (all primary prevention), with the cost of statins varied from £100 to £800 per year.
RESULTS—The costs per life year gained according to annual CHD event risk were: for 4.5%, £5100; 3.0%, £8200; 2.0%, £10 700; and 1.5%, £12 500. Reducing the cost of statins increases cost effectiveness, and narrows the difference in cost effectiveness across the range of CHD event risks.
CONCLUSIONS—At current prices statin treatment for secondary prevention, and for primary prevention at a CHD event risk 3.0% per year, is as cost effective as many treatments in wide use. Primary prevention at lower CHD event risks (< 3.0% per year) is less cost effective and unlikely to be affordable at current prices and levels of health service funding. As the cost of statins falls, primary prevention at lower risk levels becomes more cost effective. However, the large volume of treatment needed will remain a major problem.


Keywords: coronary artery disease; cost effectiveness; statins; primary prevention; secondary prevention
PMCID: PMC1729169  PMID: 10455083
11.  Evidence that an HLA-DQA1-DQB1 haplotype influences susceptibility to childhood common acute lymphoblastic leukaemia in boys provides further support for an infection-related aetiology. 
British Journal of Cancer  1998;78(5):561-565.
Comparison of DQA1 and DQB1 alleles in 60 children with common acute lymphoblastic leukaemia (c-ALL) and 78 newborn infant control subjects revealed that male but not female patients had a higher frequency of DQA1*0101/*0104 and DQB1*0501 than appropriate control subjects. The results suggest a male-associated susceptibility haplotype in c-ALL and supports an infectious aetiology.
PMCID: PMC2063058  PMID: 9744491
12.  Variations in use of cardiology services in a health authority: comparison of coronary artery revascularisation rates with prevalence of angina and coronary mortality. 
BMJ : British Medical Journal  1997;314(7076):257-261.
OBJECTIVE: To explore the relation between rates of coronary artery revascularisation and prevalence of angina to assess whether use of health services reflects need. DESIGN: Prevalence of angina symptoms determined by postal questionnaire on 16750 subjects (18 to 94 years). Comparison of data on use of coronary artery revascularisation with prevalence of symptoms and mortality from coronary heart disease. SETTING: Health authority with population of 530000. SUBJECTS: Patients admitted to hospital for coronary heart disease; patients who died; and patients undergoing angiography, angioplasty, or coronary artery bypass graft. Cohort of 491 people with symptoms from survey. MAIN OUTCOME MEASURES: Pearson's product moment correlation coefficients for relation between variables. RESULTS: Overall, 4.0% (95% confidence interval 3.7% to 4.4%) of subjects had symptoms. Prevalences varied widely between electoral wards and were positively associated with Townsend score (r = 0.79; P < 0.001), as was mortality, but the correlation between admission rates and Townsend score was less clear (r = 0.47; P < 0.01). Revascularisation rate and Townsend score were not associated. The ratio of revascularisation to number experiencing symptoms was inversely related to Townsend score (r = 0.67; P < 0.001). The most deprived wards had only about half the number of revascularisations per head of population with angina than did the more affluent wards. In affluent wards 11% (13/116) of those with symptoms had coronary angiograms compared with only 4% (9/216) in poorer wards (chi 2 = 4.96; P = 0.026). Townsend score also inversely correlated with revascularisations per premature death from coronary heart disease (r = 0.55; P < 0.01) and revascularisations per admission for myocardial infarction (r = 0.47; P < 0.01). CONCLUSION: The use of interventional cardiology services is not commensurate with need, thus exhibiting the inverse care law.
PMCID: PMC2125748  PMID: 9022488
13.  Copper chelation-induced reduction of the biological activity of S-nitrosothiols. 
British Journal of Pharmacology  1995;114(5):1083-1089.
1. The effect of copper on the activity of the S-nitrosothiol compounds S-nitrosocysteine (cysNO) and S-nitrosoglutathione (GSNO) was investigated, using the specific copper chelator bathocuproine sulphonate (BCS), and human washed platelets as target cells. 2. Chelation of trace copper with BCS (10 microM) in washed platelet suspensions reduced the inhibition of thrombin-induced platelet aggregation by GSNO; however, BCS had no significant effect on the anti-aggregatory action of cysNO. BCS inhibited cyclic GMP generation in response to both cysNO and GSNO. 3. The effect of BCS was rapid (within 30 s), and could be abolished by increasing the platelet concentration to 500 x 10(9) l-1. 4. In BCS-treated platelet suspensions, the addition of Cu2+ ions (0.37-2.37 microM) led to a restoration of both guanylate cyclase activation and platelet aggregation inhibition by GSNO. 5. The anti-aggregatory activity of GSNO was reduced in a concentration-dependent manner by the copper (I)-specific chelators BCS and neocuproine, and to a smaller extent by desferal. No effect was observed with the copper (II) specific chelator, cuprizone, the iron-specific chelator, bathophenanthroline sulphonate, or the broader-specificity copper chelator, D-penicillamine. 6. In both BCS-treated and -untreated platelet suspensions, cys NO was more potent than GSNO as a stimulator of guanylate cyclase. In BCS-treated platelet suspensions there was no significant difference between the anti-aggregatory potency of cysNO and GSNO; however, in untreated suspensions, GSNO was significantly more potent than cysNO. Thus, when copper was available, GSNO produced a greater inhibition of aggregation than cysNO, despite being a less potent activator of guanylate cyclase.(ABSTRACT TRUNCATED AT 250 WORDS)
PMCID: PMC1510308  PMID: 7780643
15.  Harm minimisation for drug misusers. 
BMJ : British Medical Journal  1992;304(6839):1441.
PMCID: PMC1882207  PMID: 1628029
16.  The role of prostanoid TP- and DP-receptors in the bronchoconstrictor effect of inhaled PGD2 in anaesthetized guinea-pigs: effect of the DP-antagonist BW A868C. 
British Journal of Pharmacology  1990;100(4):761-766.
1. In anaesthetized, pump-ventilated guinea-pigs, bolus intravenous injection of prostaglandin D2 (PGD2 5-160 micrograms kg-1) caused a dose-dependent rise in both heart rate and systemic mean arterial blood pressure with only a small monophasic rise in pulmonary inflation pressure (PIP). 2. In contrast, inhaled PGD2 (0.1-1 mg ml-1, 30s) provoked a substantial concentration-dependent biphasic rise in PIP. The bronchoconstrictor action of inhaled PGD2 was accompanied by minimal cardiovascular effects. 3. The 3-benzyl substituted hydantoin BW A868C (0.1-1 mg kg-1 i.v.) a novel prostanoid DP-receptor antagonist, had no significant effect on the cardiovascular or bronchoconstrictor effects of intravenously administered or inhaled PGD2. 4. However, BW A868C (0.1-1 mg kg-1 i.v.) did inhibit the hypotensive actions of the DP-receptor agonist, BW 245C (1-3 micrograms kg-1 i.v.). 5. The prostanoid TP-receptor antagonist BM 13.177 (2.5 mg kg-1 i.v.) strongly inhibited the bronchoconstrictor effect of inhaled PGD2, abolishing the first phase of this response and reducing the peak increase in PIP provoked by PGD2 (0.1 or 1 mg ml-1 for 30 s), by 67 +/- 16% and 44 +/- 5% respectively. 6. A combination of BW A868C (0.1 or 1 mg kg-1 i.v.) with BM 13.177 (2.5 mg kg-1 i.v.) produced no greater inhibition of the bronchoconstrictor effect of inhaled PGD2 than that seen with BM 13.177 (2.5 mg kg-1 i.v.) alone. 7. Neither bilateral vagotomy, nor selective inhibition of arachidonate cyclo-oxygenase with indomethacin or 5-lipoxygenase with the novel acetohydroxamic acid BW A4C, significantly reduced the bronchoconstrictor effect of inhaled PGD2.(ABSTRACT TRUNCATED AT 250 WORDS)
PMCID: PMC1917592  PMID: 2119842
17.  Human atrial natriuretic factor and renin-aldosterone in paracetamol induced fulminant hepatic failure. 
Gut  1991;32(1):85-89.
It has been postulated that deficiency of a putative natriuretic factor, or resistance to such a factor, may contribute to sodium retention in fulminant hepatic failure. Levels of plasma human atrial natriuretic factor (h-ANF), plasma renin activity, and aldosterone concentration were measured in 33 patients with fulminant hepatic failure due to paracetamol overdose, and 12 healthy control subjects. Levels of h-ANF were raised only in patients with evidence of severe renal impairment (serum creatinine greater than 300 mumol/l and urine output less than 100 ml/24 hours). h-ANF values were median 4.15, range 2-9 pmol/l and 10.1, 1-25 pmol/l for the control and severe renal impairment groups respectively (p less than 0.001). In the latter plasma renin activity was raised compared to that in control subjects (median 19.8, range 1.04-41.7 and 2.86, 1.87-5.9 pmol/l/h respectively, p less than 0.02). Plasma aldosterone concentration was also raised in patients (2176, 199-6894 pmol/l compared to 368, 133-578 pmol/l in control subjects, p less than 0.01). Haemodialysis induced changes in circulating h-ANF which correlated with volume and right atrial pressure changes (p less than 0.001 and p less than 0.05 respectively). In six patients with no or mild renal failure infusion of 900 ml 5% human albumin solution caused a significant increase in plasma h-ANF (p less than 0.05) without natriuresis or diuresis, a finding compatible with the hypothesis that there may be resistance to h-ANF in this group. The present findings indicate that there is no deficiency of h-ANF in fulminant hepatic failure and that known mechanisms of h-ANF release are not impaired.
PMCID: PMC1379220  PMID: 1825077
18.  Opsonic effect of jacalin and human immunoglobulin A on type II group B streptococci. 
Infection and Immunity  1990;58(11):3663-3670.
This study examined the effect of immunoglobulin A (IgA) and the IgA-binding lectin jacalin on the phagocytosis of type II group B streptococci (GBS). Strains possessing the trypsin-sensitive and trypsin-resistant components of the c protein (II/c) and type II GBS lacking the c protein (II) were examined by radiolabeled bacterial uptake, bactericidal assays, and electron microscopy. Type II/c GBS resisted phagocytosis by monocytes (4.9% +/- 0.8% uptake, mean +/- SE, n = 25) compared with type II GBS (8.5% +/- 1.4% uptake, n = 14, P = 0.03). Phagocytic killing by polymorphonuclear leukocytes was also less for the type II/c strain 78-471 than for the type II strain 79-176 (68% +/- 5% versus 86% +/- 4% reduction in CFU at 45 min, P = 0.03). IgA binding did not explain the resistance of type II/c GBS to phagocytosis. The uptake of type II/c GBS was not significantly different after opsonization in cord sera lacking endogenous IgA (5.93% +/- 1.4%) than in the same cord sera after addition of exogenous IgA (5.48% +/- 1.4%, P = 0.69, n = 9). Attempts to remove serum IgA with the IgA-binding lectin jacalin resulted in the binding of IgA-jacalin complexes to II/c GBS. This combination of nonspecific IgA and jacalin increased uptake of II/c GBS from 4.9% +/- 0.8% to 11.8% +/- 1.9% (P = 0.002). Jacalin also combined with specific, immune, monoclonal IgA bound to the surface of Haemophilus influenzae and promoted the uptake of these bacteria. Jacalin and IgA mediated phagocytosis of II/c GBS via receptors that were not dependent on divalent cations and that were not modulated by plating monocytes on antigen-antibody complexes.
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PMCID: PMC313712  PMID: 2228238
19.  Nonimmune binding of human immunoglobulin A to type II group B streptococci. 
Infection and Immunity  1990;58(6):1789-1795.
The binding of 125I-labeled human myeloma immunoglobulin A (IgA) to four type II strains and one nontypable strain of group B streptococci was measured after streptococcal chains were broken by brief sonication. Some IgA binding was observed with all strains, but specific binding (binding that was inhibited by excess unlabeled IgA, was dose dependent, and was saturable) occurred only with those strains possessing the trypsin-sensitive beta component of the c protein. Similar amounts of binding were observed with myeloma IgA and IgA1 purified from normal serum. Specific binding was more rapid at 25 degrees C than at 0 or 37 degrees C and reached a plateau in 6 to 8 h. Binding was drastically reduced (85 to 90%) when streptococci had been heated (90 degrees C for 1 h). Most radioactivity bound to group B streptococci could be displaced (greater than 60% in 3 days) by the addition of excess unlabeled IgA. The binding capacity of one strain (10(8) streptococci in 1 ml of buffer) was saturated by approximately 24 micrograms of IgA. When transformed for Scatchard analysis, these data indicated that there was a specific binding capacity of 16,000 molecules of monomeric serum IgA per single streptococcal cell. The dissociation constant for IgA binding was 19.3 nM. Since enzyme-linked immunosorbent assay studies showed that the myeloma IgA used for the studies described above was IgA1, our quantitative data apply only to the binding of this subclass to group B streptococci. However, an enzyme-linked immunosorbent-filtration assay showed that both IgA1 and IgA2 bound to a type II group B streptococcus bearing the c protein.
PMCID: PMC258724  PMID: 2187808
20.  Immediate anaphylactic bronchoconstriction induces airway hyperreactivity in anaesthetized guinea-pigs. 
British Journal of Pharmacology  1988;94(3):663-668.
1. The possible acute occurrence of airway hyperreactivity after immediate-type bronchial anaphylaxis has been investigated in anaesthetized guinea-pigs actively sensitized to ovalbumin (OA). 2. Aerosol challenge (OA 10 mg ml-1, 5 s) provoked immediate bronchoconstriction which was substantially, although incompletely, reversed by isoprenaline (Iso) infusion (1 microgram kg-1 min-1) for 10 min). 3. Bronchoconstrictor responses to 5-hydroxytryptamine (5-HT) were enhanced in challenged animals when compared to those in non-challenged animals that had also received Iso. This was seen as a leftward shift in the location of the dose-response curve for the bronchoconstrictor effect of 5-HT (dose-ratio 2.45, 95% confidence limits 1.77-3.38; P less than 0.01). This phenomenon was associated with pulmonary infiltration of polymorphonuclear leukocytes, which was not modified by Iso treatment. 4. Iso infusion alone caused a slight enhancement of airway reactivity seen as a small leftward shift of the dose-response curve for the bronchoconstrictor effect of 5-HT (dose-ratio 1.51, 95% confidence limits 1.07-2.13; P less than 0.05). 5. These results support a causal relationship between acute pulmonary inflammation and airway hyperreactivity in an animal model of human allergic asthma.
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PMCID: PMC1854033  PMID: 3179606
21.  Selective inhibition of arachidonate 5-lipoxygenase by novel acetohydroxamic acids: effects on bronchial anaphylaxis in anaesthetized guinea-pigs. 
British Journal of Pharmacology  1988;94(2):540-546.
1. The effect of a novel series of orally-active acetohydroxamic acid inhibitors of arachidonate 5-lipoxygenase on 'leukotriene-dependent' anaphylactic bronchoconstriction has been investigated in anaesthetized, pump-ventilated guinea-pigs actively sensitized to ovalbumin (OA). In a complementary series of experiments, the pharmacokinetics of these compounds in the plasma compartment following oral administration to guinea-pigs has also been investigated. 2. In animals pretreated with mepyramine (2 mg kg-1, i.v.) and indomethacin (10 mg kg-1, i.v.) and challenged with antigen aerosol (OA 10 mg ml-1; 5 s) compounds BW A4C, BW A137C and BW A797C (10-200 mg kg-1, p.o., 1 h pre-challenge) markedly reduced that component of anaphylactic bronchoconstriction shown to be 'leukotriene-dependent'. 3. The maximum degree of inhibition (up to 75%) of 'leukotriene-dependent' anaphylactic bronchoconstriction by these three compounds was equivalent to that seen with the leukotriene antagonist FPL 55712 (10 mg kg-1, i.v.). 4. The peak levels of unchanged acetohydroxamic acids in the plasma compartment occurred 0.5 h after their oral administration and were as follows: BW A4C: 11.3 +/- 3.9; BW A137C: 7.6 +/- 2.4; BW A797C: 3.9 +/- 1.3 micrograms ml-1 plasma. 5. The inhibition by BW A4C and BW A137C (50 mg kg-1, p.o.) of 'leukotriene-dependent' anaphylactic bronchospasm persisted for up to 3 and 4 h respectively but did not extend to 6 h. The decline in inhibitory activity paralleled the fall in the concentration of unchanged drug in the plasma compartment over this time period.(ABSTRACT TRUNCATED AT 250 WORDS)
PMCID: PMC1853972  PMID: 3395791
22.  Pharmacological modulation of bronchial anaphylaxis induced by aerosol challenge in anaesthetized guinea-pigs. 
British Journal of Pharmacology  1987;91(3):701-708.
Anaphylactic bronchoconstriction provoked by aerosol challenge, and its pharmacological modulation, has been investigated in anaesthetized pump-ventilated guinea-pigs actively sensitized to ovalbumin (OA). Aerosol challenge (OA 0.03-10 mg ml-1) provoked immediate bronchoconstriction, the degree of which, and its rate of development, was directly related to antigen concentration. Concomitant changes in heart rate and systemic arterial blood pressure following aerosol challenge were reduced compared with systemic (OA, 1 mg kg-1 i.v.) challenge. Unlike systemic challenge, aerosol challenge did not cause a concomitant fall in either circulating leukocyte or platelet count. When a submaximal (microshock) aerosol challenge stimulus (OA, 0.3 mg ml-1, 5 s) was employed, bronchoconstriction was markedly reduced by mepyramine (2 mg kg-1 i.v.). The residual component of bronchoconstriction was enhanced by indomethacin (10 mg kg-1 i.v.), an effect which was reversed by either BW755C (30 mg kg-1 i.v.) or FPL55712 (10 mg kg-1 i.v.). When a supramaximal (macroshock) aerosol challenge stimulus (OA, 10 mg ml-1, 5 s) was employed, bronchoconstriction was also markedly reduced by mepyramine. Residual bronchoconstriction was not altered by indomethacin, slowed but not reduced by indomethacin plus BW755C, and substantially reduced by indomethacin plus FPL55712. The successive incremental antagonism of anaphylactic bronchoconstriction by mepyramine and mepyramine plus indomethacin and FPL55712 indicates that the predominant mediators involved are histamine and leukotrienes, respectively. The failure of indomethacin plus BW755C to inhibit the mepyramine-resistant bronchoconstriction provoked by OA macroshock may reflect the increased generation of leukotrienes via a 5-lipoxygenase isoenzyme resistant to inhibition by BW755C.(ABSTRACT TRUNCATED AT 250 WORDS)
PMCID: PMC1853565  PMID: 3607373
23.  Effect of differences in antibody and complement requirements on phagocytic uptake and intracellular killing of "c" protein-positive and -negative strains of type II group B streptococci. 
Infection and Immunity  1987;55(5):1243-1251.
The influence of antibody and complement on the polymorphonuclear leukocytic uptake and killing of type II group B streptococci (GBS) was examined with 11 adult sera and three type II strains possessing the trypsin-resistant and trypsin-sensitive components (II/TR+TS) of the "c" (formerly Ibc) protein or two type II strains lacking both components (II/no c) of the c protein. All tested sera mediated a greater than 1 log10 reduction in colony-forming units (CFUR) of a type II/no c strain, even in the absence of measurable type-specific antibody (less than 1.08 micrograms/ml), but only 5 of 11 mediated a greater than 1 log10 CFUR of any type II/TR/TS strain, even in the presence of moderate levels of type-specific antibody. The classical pathway of complement activation appeared to be more important than the alternative pathway, and even absorbed or immunoglobulin G (IgG)-depleted serum (IgG, 10 mg/dl) mediated a greater than 1 log10 CFUR without magnesium ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (magnesium EGTA) chelation. Chelation with magnesium EGTA reduced the CFUR in 4 of 11 test sera and greatly reduced the CFUR in absorbed or IgG-depleted sera for type II/no c strains. Despite variation in the phagocytic killing of two representative strains of type II GBS, both strains were well phagocytized, as measured by radiolabeled bacterial uptake or electron microscopy. This study suggested that poorly killed type II/TR+TS GBS were easily phagocytized but apparently resisted intracellular killing.
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PMCID: PMC260497  PMID: 3552996
24.  Phenolic glycolipid 1 of Mycobacterium leprae causes nonspecific inflammation but has no effect on cell-mediated responses in mice. 
Infection and Immunity  1984;46(3):802-808.
The involvement of the phenolic glycolipid from Mycobacterium leprae in cell-mediated immunity has been investigated in this study. The phenolic glycolipid itself does not appear to stimulate cell-mediated immunity directly, as shown by its failure to elicit a classical delayed-type hypersensitivity response in mice immunized with M. leprae or to stimulate M. leprae-immune lymph node cells in a lymphoproliferative assay. Intradermal vaccination with the phenolic glycolipid failed to influence the growth of M. leprae in mouse footpads. A nonspecific inflammatory response to the sonicated glycolipid was observed in mice vaccinated with whole M. leprae and in control animals. No evidence was obtained for any adjuvant or suppressive effect on cell-mediated immunity by the phenolic glycolipid either to M. leprae or an unrelated antigen (sheep erythrocytes); neither sensitization nor elicitation to either antigen was affected.
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PMCID: PMC261616  PMID: 6389362
25.  Modulation of bronchoconstrictor responses to histamine in pithed guinea-pigs by sympathetic nerve stimulation. 
British Journal of Pharmacology  1982;77(2):249-254.
1 Electrical stimulation (40V, 0.5-8 Hz, pulse width 0.5 ms) of the thoracic spinal outflow for between 10 and 120 s inhibited histamine-induced bronchoconstriction in pithed guinea-pigs. 2 The degree of this bronchodilatation varied with the position of the stimulating electrode within the spinal canal. Two maxima were identified. The first, at the level of the 9th and 10th thoracic vertebrae, was abolished by adrenalectomy. The second, at the level of the 3rd and 4th thoracic vertebrae, was associated with tachycardia and was unchanged by adrenalectomy. 3 The magnitude of this second bronchodilator effect varied with the frequency of stimulation. It was abolished by pretreatment with reserpine (5 mg/kg i.p. 48 and 24 h beforehand) and was competitively blocked by propranolol (0.01-1.0 mg/kg). 4 These observations are consistent with the view that bronchodilator tone is derived from neuronally-released noradrenaline within the lung. The noradrenaline probably overflows from well-innervated vasculature adjacent to sparsely innervated airways.
PMCID: PMC2044594  PMID: 7139187

Results 1-25 (34)