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Biomedical subjects

B Robertson

Publications and source records attributed to B Robertson.

At least 145 records · Page 8Linked to original sources

The Chief Scientist reports... Behavioural risk factors for coronary heart disease and cancers among adults in Edinburgh and Glasgow: assessing change 1988-1995.

OBJECTIVE: To assess change over time in selected behavioural risk factors for coronary heart disease and cancers and to assess progress towards government-defined health targets. DESIGN: Computer assisted telephone interview survey, randomly selected sample. SETTING: Edinburgh and Glasgow. SUBJECTS: 34,247 aged 18-60 years; 43.2% male and 56.8% female. MAIN OUTCOME MEASURES: Changes in cigarette smoking, diet, alcohol use and exercise among adults between 1988 and 1995. RESULTS: A majority of the variables under study showed significant change over the time period under review. On the positive side, the percentage of female smokers decreased significantly, whilst the number of female ex-smokers increased; the use of salt and butter declined significantly for men, and butter use declined significantly for women; and increasing numbers of men ate fruit in the last 24 hours and daily. On the negative side, there was no significant decrease in smoking prevalence among men; no significant increase in reported participation in physical activity for exercise for men or women, and a significant decrease in frequency of exercise for women; and the frequency of "drinking heavily on occasion' increased for both men and women. CONCLUSIONS: Significant positive changes in key health behaviours have taken place among adults resident in Edinburgh and Glasgow since 1988, particularly in relation to smoking among women and diet among men, but progress is slow and patchy.

Adult↗

Secondary structure and biophysical activity of synthetic analogues of the pulmonary surfactant polypeptide SP-C.

Native pulmonary-surfactant-associated lipopolypeptide SP-C, its chemically depalmitoylated form and several synthetic analogues lacking the palmitoylcysteine residues were analysed for secondary structure in phospholipid micelles and for biophysical activity in 1,2-dipalmitoyl-sn-glycero-3- phosphocholine/phosphatidylglycerol/palmitic acid (68:22:9, by wt.). Compared with the native molecule, with the entire poly-valyl part in a known alpha-helical conformation, depalmitoylated SP-C was found to be still mainly alpha-helical, but with an approx. 20% decrease in the helical content. A synthetic hybrid polypeptide where the entire poly-valyl alpha-helical part of native SP-C had been replaced with the amino acid sequence of a transmembrane helix of bacteriorhodopsin is also predominantly alpha-helical. In contrast, synthetic SP-C analogues lacking only the palmitoyl groups, by replacement of the palmitoylcysteine residues with cysteine, phenylalanine or serine, or lacking the positively charged amino acids by replacement with alanine, are considerably less alpha-helical than both native and depalmitoylated SP-C. The data indicate that the SP-C palmitoyl groups are important for maintenance of the alpha-helical conformation in parts of the polypeptide, and that the poly-valyl alpha-helical conformation is not fully formed in synthetic SP-C polypeptides. Furthermore, the helical structure of both native and depalmitoylated SP-C in dodecylphosphocholine micelles is very resistant to thermal denaturation, exhibiting ordered structure at 90 degrees C. The alpha-helical content grossly parallels the peptide-induced acceleration of the spreading of phospholipids at an air/water interface and the increase of surface pressure. The data suggest that the alpha-helical conformation itself, rather than just the covalent structure, is of prime importance for the biological function of synthetic pulmonary-surfactant peptides.

Amino Acid Sequence↗

Inactivation of the cloned potassium channel mouse Kv1.1 by the human Kv3.4 'ball' peptide and its chemical modification.

1. This study used the whole-cell patch clamp technique to investigate the action of a 28-mer 'inactivation peptide' based on part of the N-terminal sequence of the human Kv3.4 K+ channel (hKv3.4 peptide) on the cloned mouse brain K+ channel mKv1.1 expressed in Chinese hamster ovary (CHO) cells, and compared this with the inactivation produced by Shaker B inactivation peptide (ShB peptide). 2. Inclusion of the hKv3.4 peptide in the patch electrode (320 microM) transformed non-inactivating mKv1.1 into a rapidly inactivating current. The voltage dependence of time constants of decay and steady-state inactivation induced by hKv3.4 peptide were characteristic of an 'A-type' K+ current. 3. The hKv3.4 peptide had no effect on the voltage dependence of activation of mKv1.1, with a mid-point of activation of -8 mV, and a slope factor of 15 mV. Steady-state inactivation curves had a mid-point of inactivation of -36 mV and a slope factor of -7 mV; the time constant of recovery from inactivation at -90 mV was 1.3 s. 4. The chemical modification reagents N-bromoacetamide (NBA, 100 microM) and chloramine-T (CL-T, 500 microM) had no effect on the fast inactivation of mKv1.1 induced by ShB peptide. In contrast, the inactivation caused by hKv3.4 peptide was removed by brief exposure to NBA and CL-T. 5. Chemical modification resulted in a hyperpolarizing shift of -8 mV (CL-T) and -11 mV (NBA) in the voltage dependence of activation of mKv1.1 in the presence of hKv3.4 peptide. 6. Chemical modification was critically dependent on the presence of a cysteine residue at position 6, and not position 24, of hKv3.4 peptide. 7. NBA and CL-T caused only a slight inhibition of unmodified mKv1.1 current with no significant effect on the voltage dependence of mKv1.1 activation, and also had no effect on channel deactivation at -90 mV. 8. Chemical modification experiments were consistent with a selective action on the hKv3.4 peptide itself, specifically at the cysteine residue at position 6.

Acetamides↗

The expression of different cytochemical markers in normal and axotomised dorsal root ganglion cells projecting to the nucleus gracilis in the adult rat.

Rat lumbar dorsal root ganglion neurones projecting to the nucleus gracilis in the brainstem were retrogradely labelled with Fluoro-Gold and analysed immunocytochemically for their expression of substance P-, calcitonin gene-related peptide-, galanin-, galanin message-associated peptide-, neuropeptide Y-, nitric oxide synthase- and carbonic anhydrase-like immunoreactivity as well as affinity to Griffonia (bandeiraea) simplicifolia lectin I--isolectin B4, RT97 and to choleragenoid. The analysis was made both in uninjured rats and in rats which had been subjected to unilateral sciatic nerve transection and partial resection 3 weeks earlier. The data showed that 6% of the L4 and L5 lumbar dorsal root ganglion cells that projected to the nucleus gracilis showed substance P-like immunoreactivity. Following nerve injury, none of the nucleus gracilis-projecting dorsal root ganglion cells showed substance P-like immunoreactivity. Nineteen per cent of the investigated cell population showed calcitonin gene-related peptide-like immunoreactivity in uninjured rats, but no nucleus gracilis-projecting calcitonin gene-related peptide-positive cells were found after nerve injury. Galanin- and galanin message-associated peptide-like immunoreactivity were found in 2% and 3%, respectively, of the Fluoro-Gold-labelled cell population normally and in 22% and 14%, respectively, after injury. No neuropeptide Y-positive cells were found in the Fluoro-Gold-labelled cell population normally, but after nerve injury, 96% of this population became neuropeptide Y-positive. Nitric oxide synthase-like immunoreactivity was found in 2% of the Fluoro-Gold-labelled cells normally and in 10% after injury. Two per cent of the Fluoro-Gold-labelled cells in the normal cases were stained by Griffonia (bandeiraea) simplicifolia lectin I--isolectin B4. After injury, however, no such double labelling was found. Thirty-four per cent of the Fluoro-Gold-labelled cell population was carbonic anhydrase positive normally, and 42% after injury. Seventy-five per cent of the Fluoro-Gold-labelled cells showed RT97 immunoreactivity normally and 12% after injury. Choleragenoid-like immunoreactivity was found in 99% of the Fluoro-Gold-labelled dorsal root ganglion cells normally and 81% after injury. Immunohistochemical visualisation of choleragenoid transganglionically transported from the injured sciatic nerve combined with neuropeptide Y immunocytochemistry showed that primary afferent fibres and terminals in the nucleus gracilis contain neuropeptide Y following peripheral nerve transection. Taken together, the results indicate that peripherally axotomised nucleus gracilis-projecting neurones undergo marked alterations in their cytochemical characteristics, which may be significant for the structural and functional plasticity of this system after injury.

Afferent Pathways↗

DNA evidence: wrong answers or wrong questions?

Much of the controversy over DNA evidence is due to the way in which forensic scientific evidence has classically been presented. The orthodox approach is to consider whether two samples match according to a predetermined criterion. If they do, the fact of match is reported along with an estimate of the frequency of the characteristics. This method fails to address the questions raised in court cases, diverts argument into irrelevancies and stultifies research. Presentation of evidence in the form of likelihood ratios, on the other hand, forces the witness to answer the questions the court is interested in and makes apparent lines of research required to increase our understanding.

Blood Group Antigens↗

Rapid pH change due to bacteriorhodopsin measured with a tin-oxide electrode.

The photocurrent transient generated by bacteriorhodopsin (bR) on a tin-oxide electrode is due to pH change and not to charge displacement as previously assumed. Films of either randomly oriented or highly oriented purple membranes were deposited on transparent electrodes made of tin-oxide-coated glass. The membranes contained either wild-type or D96N-mutant bR. When excited with yellow light through the glass, the bR pumps protons across the membrane. The result is a rapid local pH change as well as a charge displacement. Experiments with these films show that it is the pH change rather than the displacement that produces the current transient. The calibration for the transient pH measurement is given. The sensitivity of a tin-oxide electrode to a transient pH change is very much larger than its sensitivity to a steady-state pH change.

Bacteriorhodopsins↗

Nosocomial transmission of hepatitis A in a pediatric hospital traced to an anti-hepatitis A virus-negative patient with immunodeficiency.

From July through October 1991, an outbreak of hepatitis A virus (HAV) infection involving 26 hospital staff, inpatients and household contacts occurred in a pediatric hospital. All ill staff members had cared for one inpatient who had profuse diarrhea with gross fecal contamination of the environment, negative HAV serology and idiopathic immunodeficiency. HAV infection in this patient was later confirmed by polymerase chain reaction. Among hospital staff HAV attack rates were highest in nursing personnel (15%). A retrospective cohort study of nurses found that the risk of infection was greatest in those who handled the source patient's soiled bed pad (relative risk, 6.7; 95% confidence intervals, 1.6, 27.8), diaper (relative risk, 5.4; 95% confidence intervals, 0.8, 39.2) or gown (relative risk, 2.9; 95% confidence intervals, 1.1, 7.8). Glove use during these activities was not associated with a lower risk of infection, possibly because of gross environmental contamination or less use than reported. This situation was unusual because the patient was HAV-infected but had negative serology, probably because of immunodeficiency. In situations of potentially extensive environmental contamination, such as with a diapered or incontinent patient with suspected or confirmed hepatitis A, careful attention to frequent handwashing is an essential protective measure; in addition strict glove use whenever entering the patient's room should be followed to provide additional protection.

Adult↗

Healthy lungs tolerate repetitive collapse and reopening during short periods of mechanical ventilation.

The possible occurrence of lung damage if alveolar units are allowed to collapse and reopen breath by breath during mechanical ventilation with normal tidal volumes was investigated. Anaesthetised, paralysed, open chest rabbits were subjected to either intrathoracic negative (NEEP; n = 6) or positive (PEEP; n = 6) end-expiratory pressure during volume controlled mechanical ventilation. Both experimental settings were preceded by a 30 min control period and followed by a 30 min recovery period during which a PEEP of 0.2 kPa was maintained. Pao2 and pulmonary compliance deteriorated significantly in the NEEP group during the experimental period and compared to ventilation with PEEP. Partial restoration of lung mechanics and blood gases was achieved during the recovery period. After an alveolar recruitment manoeuvre, this recovery was complete. Lung clearance studied by depositing an aerosol of technetium-99m-labelled diethylenetriamine pentaacetate (99mTc-DTPA) in the alveoli, was significantly faster during ventilation with NEEP compared to the PEEP group (P = 0.0002) as well as the control period (P = 0.0029). It did not recover completely during the recovery period but remained significantly faster. Light microscopic histology was normal in both groups with no evidence of inflammation or epithelial disruption. We conclude that previously healthy rabbit lungs show only a transient disturbance of lung mechanics and blood gases with repetitive collapse and re-expansion. The integrity of the alveolar microstructure is preserved. The disturbance in the alveolo-capillary permeability persists and may indicate surfactant related alveolo-capillary barrier dysfunction.

Animals↗

Effect of surfactant on nitroblue tetrazolium reduction of polymorphonuclear leucocytes stimulated with type Ia group B streptococci.

Activation of polymorphonuclear leucocytes (PMN) was investigated after incubation of adult human PMN and group B streptococci (GBS) type Ia with a type-specific polyclonal antiserum and a modified porcine surfactant (Curosurf). The level of oxidative metabolism of PMN was studied using a micromethod modification of the nitroblue tetrazolium (NBT) reduction test. GBS alone did not stimulate significant oxygen metabolite release from PMN, and incubation of PMN with surfactant alone resulted in decreased NBT reduction. After opsonization of GBS with a specific antibody, PMN were activated and the increased oxygen metabolite release was not suppressed when surfactant was added to the system. We conclude that the encapsulated GBS strain investigated needs opsonization with specific antibody to increase oxidative metabolism of PMN, and that incubation of PMN and opsonized GBS with surfactant does not interfere with NBT reduction.

Adult↗

Alveolar-to-vascular leakage of surfactant protein A in ventilated immature newborn rabbits.

We measured alveolar-to-vascular leakage of surfactant protein A (SP-A) in immature newborn rabbits delivered at a gestational age of 27 days. Experimental animals received, via a tracheal cannula, 2 ml/kg of a mixture of modified porcine surfactant (Curosurf, 80 mg/ml) and human recombinant SP-A (4 mg/ml). Littermate controls received the same volume of human SP-A in saline (4 mg/ml). After 30 min of artificial ventilation with a frequency of 40/min and an inspiration time of either 0.75 or 0.45 s, blood was sampled from the right ventricle and the lungs were lavaged. The content of human SP-A in serum and lung lavage fluid was determined with ELISA kits, and the alveolar-to-vascular leak expressed as the quotient of total SP-A in serum and lavage fluid. The leak in control animals amounted to about 2% of SP-A in lung wash and was several times higher in these animals than in those receiving surfactant. The leak was of the same order irrespective of whether the animals were ventilated with long or short inspiration time. We speculate that serum levels of SP-A may reflect the degree of lung injury in various forms of respiratory failure.

Animals↗

The effect of knee and foot position on the electromyographical activity of the superficial quadriceps.

Isometric quadriceps exercises are used early in knee rehabilitation. Varying knee or foot position is hypothesized to selectively activate specific quadriceps muscles. This study examined the activities of the vastus medialis oblique, vastus lateralis, and rectus femoris during isometric contractions at 90 degrees, 150 degrees, and 175 degrees knee angles with internally rotated, neutral, and externally rotated foot positions. Subjects performed three perceived maximal isometric contractions at each knee angle/foot position while electromyographic activity (EMG) was collected. Statistical analysis consisted of a three-way repeated measures multiple analysis of variance, with post hoc analysis as was appropriate. Although no significant differences were detected among foot positions for the rectus femoris at 90 degrees, this knee angle produced significantly greater EMG activity for the neutral position compared with 150 degrees or 175 degrees. The 90 degrees angle was also superior to 175 degrees for the externally rotated position. The results for both the vastus medialis and vastus lateralis were similar, with the 90 degrees angle producing greater EMG activity than 175 degrees in the externally rotated position. In addition, the neutral position produced significantly more activity than the internally rotated position at 90 degrees. At 150 degrees, the neutral position was superior to the externally rotated position. Finally, at the 175 degrees knee angle, the highest level of EMG activity was with the foot internally rotated. Considering the combination of effects for EMG activity across all muscles tested, the 90 degrees knee angle with a neutral foot position may provide the most effective condition for rehabilitation of all muscles tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Comprehensive management of pan-facial fractures.

In the last 20 years, the management of pan-facial injuries has progressed to the point where immediate treatment using open reduction with rigid fixation is now the standard of care. After discussing the historical progression of treatments, the authors present a plan for treatment of craniofacial injuries based on the use of incisions that expose the four areas of the face: the frontal area, upper midface, lower midface and occlusion, and the basal mandibular area. According to the authors, five incisions permit access to the entire anterior craniofacial skeleton: the coronal, lower eyelid, upper and lower gingival-buccal-sulcus, and the preauricular-retromandibular. Through these incisions, the facial buttresses can be accessed to allow reduction and rigid fixation of facial fractures.

Ear, External↗

Surfactant therapy and nasal continuous positive airway pressure for newborns with respiratory distress syndrome. Danish-Swedish Multicenter Study Group.

BACKGROUND: In southern Scandinavia most babies with respiratory distress syndrome are initially treated with nasal continuous positive airway pressure. We performed a multicenter trial to investigate whether the addition of a single dose of porcine surfactant administered during a short intubation before the occurrence of serious deterioration could reduce the subsequent need for mechanical ventilation. METHODS: We randomly assigned 35 infants with moderate-to-severe respiratory distress syndrome to surfactant therapy (Curosurf, 200 mg per kilogram of body weight) plus nasal continuous positive airway pressure and 33 infants to nasal continuous positive airway pressure alone. The study was not blinded. The indications for mechanical ventilation were a ratio of arterial to alveolar oxygen tension of less than 0.15, severe apneic attacks, or both. RESULTS: Six hours after randomization, when the median age of the babies was 18 hours, the mean ratio of arterial to alveolar oxygen tension was 0.37 in the surfactant-treated babies, as compared with 0.25 in the controls (P < 0.001). The need for subsequent mechanical ventilation was reduced with surfactant therapy (to 43 percent of the surfactant-treated babies as compared with 85 percent of the controls; P = 0.003). When 17 infants with ratios of arterial-to-alveolar oxygen tension of less than 0.15 at randomization were excluded, the need for mechanical ventilation was still significantly reduced in the surfactant-treated group (to 33 percent [9 of 27 babies], as compared with 83 percent [20 of 24 babies] in the control group; (P < 0.001). After 28 days, two of the surfactant-treated babies had died, as compared with five of the control babies. CONCLUSIONS: In babies with moderate-to-severe respiratory distress syndrome treated with nasal continuous positive airway pressure, a single dose of surfactant reduced the need for subsequent mechanical ventilation.

Biological Products↗

trkB-like immunoreactivity in rat dorsal root ganglia following sciatic nerve injury.

The expression of full-length trkB protein, the functional high affinity receptor for BDNF and NT-4, was examined by immunohistochemistry in adult rat L4-L5 dorsal root ganglia after different types of sciatic nerve lesions. In normal ganglia, 52.5% of the neurons showed trkB-like immunoreactivity. Size measurements demonstrated that trkB-like immunoreactivity was seen predominantly in small- and medium-sized cells. This was confirmed by the finding that 28% of all trkB-positive neurons showed affinity to RT97, an antibody which labels a neurofilament epitope specific for medium-sized and large primary afferent neurons. After crush, section or neuroma formation of the sciatic nerve, the proportion of trkB-positive cells was 64.5%, 58% and 61.9%, respectively. Since trkB-receptors are present in regenerating primary afferent neurons, these data could indicate that BDNF and/or NT-4 are involved in sensory nerve fiber regeneration after adult injury.

Animals↗