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B Robertson

Publications and source records attributed to B Robertson.

At least 217 records · Page 12Linked to original sources
PubMed1991

Properties of 5-hydroxytryptamine3 receptor-gated currents in adult rat dorsal root ganglion neurones.

1. Responses to 5-hydroxytryptamine (5-HT) were examined on rat dorsal root ganglion (DRG) neurones maintained in tissue cultures, by use of whole cell recording techniques. 2. 5-HT (usually 10 microM) evoked a depolarization associated with an increase in membrane conductance in 40% of DRG neurones. There was a considerable variation in the size and persistence of this response between different batches of cells. 3. The 5-HT response was mimicked by applying the agonists 2-methyl-5-HT (10 microM) and phenylbiguanide (10 microM). Responses were blocked by ICS 205-930 (100 nM), but not by methysergide (0.1-1.0 microM). 4. 5-HT currents could be carried by sodium and caesium ions, but not by choline ions. The amplitude and duration of the 5-HT responses were dependent on the concentration of divalent cations in the extracellular solution: both became greater when calcium and magnesium concentrations were decreased. 5. Staurosporine, a putative antagonist of protein kinases, inhibited responses to 5-HT.

Alkaloids↗
PubMed1991

Activity of pulmonary surfactant after blocking the associated proteins SP-A and SP-B.

To investigate the role of the pulmonary surfactant-associated proteins SP-A and SP-B, the respective monoclonal antibody (anti-A or anti-B) was added to porcine pulmonary surfactant at a weight ratio of 1:2, and the mixtures were tested on surfactant-deficient immature newborn rabbits (gestational age 26 days). Under pentobarbital sodium anesthesia and mechanical ventilation with a 25-cmH2O peak insufflation pressure, the tidal volumes of the animals given surfactant alone and of those given surfactant containing anti-A were 27.9 +/- 5.1 and 25.1 +/- 9.6 (SD) ml/kg, respectively, whereas that of those given surfactant with anti-B was 5.8 +/- 3.6 ml/kg (P less than 0.05). The surface adsorption times of surfactant alone and of anti-A-containing surfactant were less than 0.8 s compared with greater than 120 s (P less than 0.01) for anti-B-containing surfactant. The anti-B suppressed the surfactant activity until the weight ratio was decreased to 2:100. The role of SP-A could not be clarified, but it was concluded that SP-B is an essential factor for surfactant activity.

Animals↗
PubMed1991

The factor structure and factor stability of the hospital anxiety and depression scale in patients with cancer.

An exploratory factor analysis of the HAD was carried out in 568 cancer patients. Two distinct, but correlated, factors emerged which corresponded to the questionnaire's anxiety and depression subscales. The factor structure proved stable when subsamples of the total sample were investigated. The internal consistency of the two subscales was also high. These results provide support for the use of the separate subscales of the HAD in studies of emotional disturbance in cancer patients.

Adolescent↗
PubMed1991

Inactivation of exogenous surfactant by pulmonary edema fluid.

Modified natural porcine surfactant was mixed with edema fluid sampled from the airways of hyperoxia-exposed adult rabbits. By varying the concentration of surfactant lipids (10, 25, and 50 mg/mL) and edema fluid proteins (0-280 mg/mL), we obtained a series of preparations with protein to surfactant lipid weight ratios ranging from 0 to 11.2. The surfactant activity of these various mixtures was analyzed with a pulsating bubble (at a lipid concentration of 10 mg/mL) or in experiments on immature newborn rabbits (at lipid concentrations of 25 or 50 mg/mL). For the latter purpose, animals were delivered at a gestational age of 27 d and ventilated with a standardized sequence of insufflation pressures after receiving 0.1 mL of the surfactant-edema sample into the airways at birth. Nearly complete in vitro inhibition of surfactant (markedly delayed film adsorption and a minimum surface tension of 23 mN/m during pulsation) was observed at a protein to surfactant lipid ratio of 4.5. Under in vivo conditions, nearly complete surfactant inhibition (tidal volumes reduced to less than 20% of the values for littermates ventilated with the same pressure after receiving surfactant without admixture of edema fluid) was documented at a protein to surfactant lipid ratio of 11.2. Our data suggest that the functional properties of an immature neonatal lung, in which serum proteins tend to leak into the airspaces after the onset of ventilation, depend on the stoichiometric relation between surfactant lipids and inhibitory proteins in the lung liquid.

Animals↗
PubMed1991

Phagocytic functions and tumor necrosis factor secretion of human monocytes exposed to natural porcine surfactant (Curosurf).

In this study we have analyzed various phagocytic functions and tumor necrosis factor (TNF) secretion of human monocytes exposed to either a biochemically well-defined porcine surfactant or a purified phospholipid preparation. Adherence, random migration, and chemotactic response to zymosan activated serum and formyl-methionyl-leucyl-phenylalanine were normal in surfactant-treated monocytes; surfactant was not a chemotactic stimulus. In contrast, phagocytosis of Staphylococcus aureus by monocytes exposed to surfactant (100 micrograms/mL) or phospholipids (100 micrograms/mL) was slightly impaired [surfactant: at 30 min (t30) 48.5 +/- 11%, t60 73.3 +/- 10.1%; phospholipids; t30 47.3 +/- 2.5%, t60 68.0 +/- 6.6%; controls: t30 66.6 +/- 9.9%, t60 81.0 +/- 6.6%, p less than 0.05 at t30 for both, p less than 0.05 at t60 for phospholipids]. Due to the smaller number of S. aureus ingested, bactericidal activity of surfactant- or phospholipid-treated monocytes was slightly reduced when compared with controls. Surfactant or phospholipids had no bactericidal activity. Uptake of Candida albicans was identical in surfactant- or phospholipid-treated monocytes and untreated controls; the same was true for the number of Candida organisms ingested per cell. Phagocytosis-associated chemiluminescence and production of superoxide anion by monocytes of either source in response to phorbol myristate acetate and opsonized zymosan were also unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Experimental neonatal respiratory failure induced by a monoclonal antibody to the hydrophobic surfactant-associated protein SP-B.

The present experiments were designed to test whether selective blocking of the surfactant-associated hydrophobic polypeptide SP-B (8.7 kD) would interfere with lung function during neonatal adaptation. A MAb to porcine SP-B was produced by hybridoma cell line (8B5E); this antibody cross-reacts with rabbit SP-B. Six mg of MAb to SP-B, dissolved in 0.2 mL of saline, was instilled into the airways of near-term newborn rabbits (gestational age 29 d), before the onset of ventilation. Control animals received the same amount of nonspecific rabbit IgG in saline, or were untreated. The animals were ventilated for 120 min with a standardized tidal volume (10 mL/kg). The specific antibody caused a prominent, immediate decrease in lung-thorax compliance, associated with acute inflammatory and exudative lung lesions including hyaline membranes. IgG alone had no such effects. Our data suggest that the MAb to SP-B inhibits surfactant function in the neonatal period by blocking one of the mechanisms responsible for fast adsorption of the surfactant phospholipids to the alveolar air-liquid interface. In addition, an acute inflammatory reaction is probably triggered in the lung parenchyma by the immune reaction.

Animals↗
PubMed1991

Surfactant substitution in ventilated very low birth weight infants: factors related to response types.

We investigated factors than may influence the response to surfactant substitution. Thirty-five very low birth weight infants with respiratory distress syndrome were treated with Curosurf at 3-12 h of age. From the changes in oxygenation, the therapeutic response was categorized as rapid and sustained, rapid with relapse, or poor. Phospholipids and surfactant protein A were quantified in gastric aspirate samples obtained immediately after birth. They showed that 16 infants had accelerated lung maturity, despite clinical and radiologic signs of respiratory distress syndrome. Ten of them had suffered from birth asphyxia or connatal infection. Nevertheless, 12 of these 16 infants responded rapidly to surfactant substitution. Poor response was seen in four infants with connatal infection. Of 19 infants with immature lung profile, 18 showed a rapid initial response to surfactant substitution. Dynamic compliance of the respiratory system or arterial blood pressure before substitution, the ultrastructure of the surfactant preparation, or persistence of the ductus arteriosus did not influence the response type, but fraction of inspired oxygen was higher before surfactant substitution in infants with poor response. Prognosis was related to short-term response: Of 17 infants who showed a rapid and sustained response, none died, whereas eight of 18 infants with relapse after rapid initial response or poor response died (p less than 0.05). We conclude that surfactant substitution may be beneficial not only in babies with primary surfactant deficiency but also in other pulmonary disorders that are common in very low birth weight infants. The type of response may be of prognostic value.

Biological Products↗
PubMed1991

Application of a new ventilator-multi-plethysmograph system for testing efficacy of surfactant replacement in newborn rabbits.

We applied a new ventilator-multi-plethysmograph system to evaluate the effect of surfactant replacement in newborn rabbits under well controlled, nearly physiological conditions characterized by normal ECG and adequate PCO2 in right ventricular heart blood obtained at the end of the experiment. Up to 10 animals were ventilated in parallel with a pressure-constant common respirator system. Using a working pressure of 4.9 kPa (50 cmH2O), we could adjust the pressure delivered to each animal within the range of 0.49-4.4 kPa (5-45 cmH2O), by changing the length of an open high-resistance tube constituting the outflow limb of the connection between the common ventilator tube and the tracheal cannula. Immature newborn animals obtained after 27.5 days gestation and ventilated for 30 min with a tidal volume of 8-10 ml.kg-1 had a mean +/- SD lung-thorax compliance of 4.2 +/- 1.1 ml.kPa-1.kg-1 (0.41 +/- 0.11 ml.cmH2O-1.kg-1) and PCO2 of 8.5 +/- 1.9 kPa. In littermates treated at birth with a large dose of natural surfactant (Curosurf, 200 mg.kg-1, compliance increased to 6.0 +/- 1.0 ml.kPa-1.kg-1 (0.68 +/- 0.10 ml.cmH2O-1.kg-1) (p less than 0.01) and PCO2 decreased to 6.9 +/- 1.2 kPa (p less than 0.01). Near-term animals, obtained at 30 days gestation and ventilated under similar conditions had a compliance of 7.2 +/- 0.9 ml.kPa-1.kg-1 (0.71 +/- 0.09 ml.cmH2O-1.kg-1) and PCO2 of 6.4 (1.2) kPa. Administration of surfactant (same dose as above) to these mature animals at birth had no adverse effects.

Animals↗
PubMed1990

Wheat germ agglutinin binding in rat primary sensory neurons: a histochemical study.

The binding of wheat germ agglutinin (WGA) to L5 dorsal root ganglion (DRG) cells in the rat was studied with the WGA-FITC conjugate. These cells were also examined with regard to overlap between WGA staining and choleragenoid-like immunoreactivity. The DRG cells showed varying intensity of the staining, which was confined to the cytoplasm. The majority of the small cells were heavily stained, whereas the large cells showed less or occasionally no staining. Lectin binding was observed along nerve fibres in the ganglion, and appeared to be localized to the Schwann cells and to the nodes of Ranvier. Strong staining was also observed in the area surrounding the ganglion cells and seemed to be confined to the satellite cells. A subpopulation of the ganglion cells showed both WGA-staining and choleragenoid-like immunoreactivity. These results indicate a nonuniform affinity of WGA for different subpopulations of DRG neurons.

Animals↗
PubMed1990

European multicenter trials of curosurf for treatment of neonatal respiratory distress syndrome.

Curosurf, a preparation of polar lipids and hydrophobic proteins isolated from porcine lungs by liquid-gel chromatography, is currently used in European multicenter trials for prevention and treatment of neonatal respiratory distress syndrome (RDS). In babies requiring artificial ventilation with 60-100% oxygen, tracheal instillation of a single dose of Curosurf (200 mg/kg) leads to a dramatic improvement of gas exchange and reduced mortality, without increasing the incidence of neurodevelopmental handicap among survivors. Several factors, including high ventilator pressure and oxygen requirements, have a negative impact on the therapeutic response, suggesting that the patients should be treated at a comparatively early stage of the disease. Clinical trials testing this hypothesis, as well as the effect of multiple treatment doses, are in progress.

Europe↗
PubMed1990

Early versus late surfactant replacement therapy in severe respiratory distress syndrome.

26 preterm infants with severe respiratory distress syndrome (RDS) have been treated at different ages with a single dose of natural porcine surfactant (Curosurf, 200 mg/kg). Criteria for treatment included clinical and radiological signs of severe RDS (grade III-IV), requirement of artificial ventilation and an FiO2 greater than or equal to 0.6. Nineteen neonates have been subjected to early treatment (2-15 h of age, mean birth weight SD: 1201 +/- 387 g) and 7 patients to late treatment (greater than 15 h to 48 h of age, birth weight SD 1624 +/- 649 g). Average FiO2 before treatment was 0.88 in early-treated patients and 0.8 in late-treated patients, age at treatment was 4.6 h and 36 h, respectively (median). Both early- and late-treated infants exhibited an improvement in oxygenation (more than twofold increase of the PaO2/FiO2 ratio) within 5 minutes after initiation of therapy. Average duration of intermittent pressure ventilation was 15 days in the early treatment group and 19 days in the late treatment group. Total exposition to greater than 21% oxygen was 21 days in early-treated and 48 days in late-treated infants. Pneumothorax occurred in none of the patients. All early treated infants survived without signs of severe bronchopulmonary dysplasia (BPD greater than 21% O2, greater than 90 days plus radiological changes). However, two out of seven late-treated infants developed severe BPD; one patient died as a consequence of cardiopulmonary deterioration. Two patients in the early treatment group died of nonpulmonary complications. We conclude that surfactant replacement therapy should probably be initiated as soon as possible after manifestation of severe RDS.

Birth Weight↗
PubMed1990

Michaelis-Menten equation for an enzyme in an oscillating electric field.

The electric charges on an enzyme may move concomitantly with a conformational change. Such an enzyme will absorb energy from an oscillating electric field. If in addition the enzyme has a larger association constant for substrate than for product, as is often true, it can use this energy to drive the catalyzed reaction away from equilibrium. Approximate analytical expressions are given for the field-driven flux, electrical power absorbed, free-energy produced per unit time, thermodynamic efficiency, and zero-flux concentrations. The field-driven flux is written as a generalized Michaelis-Menten equation.

Biological Transport, Active↗
PubMed1990

Kinetics of a multistate enzyme in a large oscillating field.

A simple, general, and efficient method for calculating the response of a set of coupled first-order (or pseudo-first-order) chemical reactions to an arbitrarily large periodic field is described. The method is applied to a four-state membrane transport enzyme that is electroconformationally coupled to an ac field, i.e., the enzyme has electric charges that move concomitantly with a conformational transition. The calculation is done both for enzymes in a planar membrane and for enzymes in the spherical membrane of a cell or vesicle in suspension.

Enzymes↗
PubMed1990

[Surfactant substitution in severe respiratory distress syndrome in premature infants weighing less than 1,000 g].

19 preterm infants with severe respiratory distress syndrome (RDS) were treated with a single dose of natural porcine surfactant (Curosurf, 200 mg/kg). 9 patients had a birth weight of less than 1000 g (845 +/- 112 g, mean +/- SD and the mean gestational age was 27.2 +/- 2.1 weeks). The other 10 had a birth weight of greater than 1000 g (1521 +/- 218 g and a mean gestational age 31 +/- 2.8 weeks). Age at treatment was 3 h in infants less than 1000 g and 4 h in patients greater than 1000 g. Both groups of infants showed a rapid improvement in oxygenation and gas exchange within minutes after surfactant replacement. Exposition to greater than 60% and greater than 40% oxygen was identical in both groups. However, time in greater than 21% oxygen was significantly longer in infants less than 1000 g (median 30 days, 8.5 days in patients greater than 1000 g, p less than 0.01). The duration of mechanical ventilation was 33 days, in patients greater than 1000 g and 5 days; p less than 0.01. None of the infants developed a pneumothorax, but 6 out of 9 patients less than 1000 g developed mild bronchopulmonary dysplasia. 2 infants less than 1000 g died at day 5 and day 11 from cardio-circulatory arrest following ligation of a patent ductus arteriosus, and nosocomial septicaemia, respectively. Prolonged mechanical ventilation and exposure to oxygen in patients less than 1000 g cannot be attributed to surfactant deficiency alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Birth Weight↗
PubMed1990

Hydrophobic surfactant-associated polypeptides: SP-C is a lipopeptide with two palmitoylated cysteine residues, whereas SP-B lacks covalently linked fatty acyl groups.

Pulmonary surfactant contains two hydrophobic polypeptides, SP-B and SP-C, with known amino acid sequences and with truncated subforms lacking the N-terminal residues. Treatment of SP-C with KOH releases fatty acids (palmitic acid to more than 85%) in molar ratios of 1.8-2.0 relative to the polypeptide. Furthermore, plasma-desorption mass spectrometry shows native SP-C of both the intact and truncated types to be monomers with masses about 500 units higher than those expected for the polypeptide chains. After treatment with KOH, trimethylamine, or dithioerythritol, the polypeptide masses are obtained. These results prove that native SP-C is a lipopeptide with two palmitoyl groups covalently linked to the polypeptide chain. The deacylation conditions, the presence of two cysteine residues in the polypeptide, and the absence of other possible attachment sites establish that the palmitoyl groups are thioester-linked to the two adjacent cysteine residues. In contrast, the major form of porcine SP-B is a dimer without fatty acid components. That SP-C is a true lipopeptide with covalently bound palmitoyl groups suggests possibilities for functional interactions. It gives a direct physical link between SP-C and surfactant phospholipid components. Long-chain acylation may constitute a means for association of proteins with membranes and could conceivably modulate the stability and biological activity of surfactant films.

Amino Acid Sequence↗
PubMed1990

Passive expiratory flow-volume recordings in immature newborn rabbits. Effect of surfactant replacement on the time constant of the respiratory system.

Immature newborn rabbits with a gestational age of 27 days were paralyzed and kept in body plethysmographs. They were ventilated for 10 min with a tidal volume of approximately 10 ml/kg, with or without previous surfactant treatment via the airways. Tidal volumes and flow were recorded with a pneumotachograph connected to the body plethysmograph, and the expiratory time constant of the respiratory system (trs) was determined from flow-volume diagrams. The values of trs after 10 min were significantly higher in surfactant-treated animals than in controls (50 +/- 7 vs. 23 +/- 4 ms; p less than 0.002), indicating stabilization of the alveoli. There was also a close correlation between trs and the compliance values calculated from tidal volumes and ventilator pressure (r = 0.80; p less than 0.001), as well as between trs and the alveolar volume density in histological lung sections, determined by automated image analysis (r = 0.71; p less than 0.001).

Animals↗
PubMed1990

Surfactant replacement in spontaneously breathing babies with hyaline membrane disease--a pilot study.

In a neonatal unit which, at that time, had no facilities for artificial ventilation, 14 newborn infants with birth weight greater than or equal to 1,500 g fulfilling the diagnostic criteria for severe hyaline membrane disease (HMD) were treated by tracheal instillation of bovine surfactant (200 mg/kg). Twelve of these babies showed increased transcutaneous PO2/FiO2 ratio within 2 min, the average therapeutic response being sustained for at least 72 h. One of the two babies who did not respond to treatment was later diagnosed as a case of group B streptococcal pneumonia. One baby with favorable initial response died from sepsis at the age of 7 days; the other patients survived without sequelae. We conclude that treatment with exogenous surfactant might be considered as an alternative to ventilator treatment in babies with severe HMD.

Animals↗