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Biomedical subjects

M Jackson

Publications and source records attributed to M Jackson.

At least 37 records · Page 2Linked to original sources
PubMed1991

Fourier transform infrared spectroscopic studies of Ca(2+)-binding proteins.

The secondary structures of calmodulin and parvalbumin are well established from X-ray diffraction and nuclear magnetic resonance spectroscopic studies, which indicate that these proteins are predominantly alpha-helical in character. Recent infrared studies have nevertheless suggested that the helical structures present in these proteins in solution are not the standard alpha-helix but rather some kind of distorted helices [Trewhella, J., et al. (1989) Biochemistry 28, 1294]. The evidence for this was the unusually low amide I frequency for calmodulin and troponin C in 2H2O solution. The studies presented here, however, suggest that the helical structures in these proteins are not significantly distorted, for two reasons. First, distorted helical structures have weaker hydrogen bonds than the standard alpha-helix and would therefore be expected to absorb at a higher rather than a lower frequency. Second, distorted helical structures would absorb at an unusual frequency in H2O solutions which is not the case for the proteins studied here. The band frequency of these proteins is observed to occur at a frequency observed with other proteins known to contain predominantly alpha-helical structures. Quantitative analysis of the FT-IR spectra of calmodulin (67% alpha-helix) and parvalbumin (68% alpha-helix) in H2O in the presence of Ca2+ gives helical contents similar to those reported by X-ray studies. This raises the question as to why these proteins in H2O show a normal frequency for the presence of alpha-helical structures and an abnormal frequency in 2H2O. Addition of deuterated glycerol to the proteins in 2H2O solutions results in a significant shift of absorbance to higher frequency.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium↗
PubMed1991

Social, neurological and cognitive disorders in alcoholics.

OBJECTIVES: To construct the social, neurological and neuropsychological profiles of patients with suspected alcohol related brain damage, and to test the hypothesis that cognitive dysfunction develops in alcoholics before signs of alcohol related neurological disease. DESIGN: The study design comprised: a retrospective analysis of patients' records; a comparison of patients' demographic and social variables with age-matched population data from the 1986 Census; and a comparison of neuropsychological test scores of male patients with suspected alcohol related brain damage and age-matched controls. SETTING: The Neuropsychology Unit of Royal Prince Alfred Hospital, a tertiary referral teaching hospital. PARTICIPANTS: All patients (n = 641) referred to the Neuropsychology Unit for assessment of suspected alcohol related brain damage from July 1, 1987 to June 30, 1989, and a control group (n = 93) consisting of healthy volunteers who drank no more than 40 g of alcohol per day. RESULTS: Of the patients, 515 (80%) were men and 410 (64%) were 55 years or younger; their median daily alcohol consumption was 180 g. Compared with the general population the patients were significantly more likely to be in receipt of social security payments, to be separated, divorced or widowed and living in rented or temporary accommodation. However, the proportion of professional and skilled individuals was the same as in the general population. Cerebellar degeneration (38%), peripheral neuropathy (34%) and seizures (14%) were the most frequent neurological disorders. Frontal lobe dysfunction (58%) and short-term memory loss (32%) were the most frequent cognitive abnormalities. Dementia was relatively uncommon (4%). The mean age of male patients with alcohol related brain damage but no neurological disorders (43 years) was significantly less than the mean age of those with neurological disease (54 years; P less than 0.001). In the former, neuropsychological tests of frontal lobe function showed significant impairment compared with control subjects (P less than 0.001), despite normal intelligence. CONCLUSIONS: Cognitive impairment in alcoholics frequently takes the form of frontal lobe dysfunction and may be relatively subtle, requiring a neuropsychological examination for diagnosis. Signs of cognitive impairment may precede those of alcohol related neurological disorders by more than ten years.

Adult↗
PubMed1991

Beware of proteins in DMSO.

The effect on the secondary structure of representative alpha-helical, beta-sheet and disordered proteins by varying concentrations of dimethyl sulphoxide (DMSO) in 2H2O has been investigated by Fourier transform infrared spectroscopy. Significant perturbations of protein secondary structure are induced by DMSO and DMSO/2H2O mixtures. For highly structured proteins, such as myoglobin and concanavalin A, the infrared spectra point to a progressive destabilisation of the secondary structure until at moderate DMSO concentrations (around 0.33 mol fraction) intermolecular beta-sheet formation and aggregation are induced, as indicated by the appearance of a strong band at 1621 cm-1. This is a direct consequence of the disruption of intramolecular peptide group interactions by DMSO (partial unfolding). At higher DMSO concentrations (above 0.75 mol fraction), such aggregates are dissociated by disruption of the intermolecular C = O...2H-N deuterium bonds. The presence of a single amide I band at 1662 cm-1 corresponding to free amide C = O groups indicates that at high concentrations and in pure DMSO the proteins are completely unfolded, lacking any secondary structure. While low concentrations of DMSO showed no detectable effect upon the gross secondary structure of myoglobin and concanavalin A, the thermal stability of both proteins was markedly reduced. In alpha-casein, a highly unstructured protein, the situation is one of direct competition. The amide I maximum in 2H2O, at 1645 cm-1, is typical of unordered proteins with C = O groups deuterium-bonded predominantly to 2H2O. Addition of DMSO disrupts such interactions by competing with the peptide C = O group for the deuterium bond donor capacity of the 2H2O, and so progressively increases the amide I maximum until it stabilizes at 1663 cm-1, a position indicative of free C = O groups.

Dimethyl Sulfoxide↗
PubMed1991

Valinomycin and its interaction with ions in organic solvents, detergents, and lipids studied by Fourier transform IR spectroscopy.

The structure of valinomycin in a range of organic solvents of varying polarity and in detergent and lipid dispersions has been studied by Fourier transform ir spectroscopy. In solvents of low polarity such as chloroform, ir spectra of valinomycin are fully consistent with the bracelet structure proposed on the basis of nmr spectroscopy, showing a single narrow amide I component attributable to the presence of beta-turns and a single band arising from nonhydrogen-bonded ester C = O groups. K+ complexation results in a downward shift in the amide I band frequency, indicating an increase in the strength of the amide hydrogen bonds, along with a shift to lower frequencies of the ester C = O absorption due to a reduction in electron density in these bonds upon complexation. Identical results were obtained with NH4+, a finding not previously reported. In solvents of both medium (CHCl3/DMSO 3:1) and high (pure DMSO) polarity, we find evidence of significant disruption of the internal hydrogen-bonding network of the peptide and the appearance of a band suggesting the presence of free amide C = O groups. In such solvents, complexation with K+ and NH4+ was not observed. The structure of valinomycin in detergent micelles resembles that in nonpolar organic solvents. However, changes were found in the amide I and ester carbonyl maxima as 2H2O penetrated the micelle which suggest significant interaction between the solvent and peptide. Complexation with K+ was reduced in cationic detergent micelles as a result of a decrease in the effective K+ concentration due to charge repulsion at the micelle surface.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1991

Operation does not increase resting energy expenditure in the neonate.

This study was designed to assess the effect of operative stress on resting energy expenditure (REE) in surgical newborn infants. REE was measured in 15 neonates who had had an abdominal or thoracic operation. The findings were compared with the REE predicted from Talbot's data for unstressed neonates. The mean measured postoperative REE of 39.18 +/- 6.44 was not significantly different from the mean predicted REE of 40.98 +/- 8.83 kcal/kg/d. We concluded that an uncomplicated operation does not increase REE in the neonate.

Energy Metabolism↗
PubMed1991

Results of balloon pulmonary valvuloplasty as a palliative procedure in tetralogy of Fallot.

Balloon pulmonary valvuloplasty was attempted in 67 patients with tetralogy of Fallot at a median age of 5 months (range 0.03 to 52 months) for relief of cyanosis. In three patients, the valve could not be crossed and an aortopulmonary shunt was performed. In 35 patients, follow-up angiography was performed 3 to 30 months (average 12) after valvuloplasty. In 24 of these 35 patients (group A), the stenosis had been adequately palliated by valvuloplasty; the other 11 patients (group B) had required an aortopulmonary shunt 1 month (range 0 to 3 months) after valvuloplasty. The two groups were similar (p greater than 0.1) with respect to age at valvuloplasty, pulmonary anulus diameter, ratio of pulmonary artery to descending aorta diameter before valvuloplasty and interval to follow-up angiography. In contrast to patients in group B, patients in group A had a significant immediate improvement in systemic arterial oxygen saturation (p less than 0.01) and a significant increase in pulmonary anulus diameter at follow-up angiography (p less than 0.001). The growth of the branch pulmonary arteries was similar (p greater than 0.1) in the two groups. Among 42 patients who have had surgical correction, a transannular patch for right ventricular outflow tract reconstruction was used in 27 (64%); there was no difference between groups A and B with respect to its use. Eight patients died (three after repair) and death could not be directly attributed to valvuloplasty in any. Balloon valvuloplasty promotes growth of the pulmonary valve anulus and pulmonary arteries and is a useful alternative to an aortopulmonary shunt in patients with small pulmonary arteries or associated complex intracardiac defects.

Angiocardiography↗
PubMed1991

The effects of high-energy feeding on energy balance and growth in infants with congenital heart disease and failure to thrive.

Failure to thrive (FTT) in infants with congenital heart disease (CHD) can be attributed to their low energy intakes and high resting energy expenditures. Energy intake, energy expenditure and growth were studied in infants with CHD on normal formula feeds and then on feeds supplemented with glucose polymer to see whether supplementation improved energy retention and growth. Mean gross energy intakes increased by 31.7% on high-energy feeding and mean weight gain improved from 1.3 g/kg per d on control to 5.8 g/kg per d on high-energy feeding. Resting oxygen consumption (VO2 ml/kg per min) was not significantly different on the two feeding regimens, although respiratory quotient rose on high-energy feeding reflecting the increased carbohydrate intake. Estimated energy costs of growth on high-energy feeding fell within the previously described range for normal infants. It is recommended that infants with CHD known to be associated with FTT are fed on high-energy diets from the time of diagnosis in order to optimize growth.

Energy Metabolism↗
PubMed1991

Reliability and validity of a psychotic traits questionnaire (STQ).

The 'schizotypal personality' (STA) and 'borderline personality' (STB) scales of the STQ were administered to two groups: normal subjects who had completed the questionnaire on a previous occasion, four years earlier, and a 'clinical' sample, consisting of members of a self-help support group for people who at some time in the past had been psychiatrically diagnosed as suffering from a psychotic illness, mainly schizophrenia. As predicted, the latter had significantly higher scores than controls on both STQ scales, certain items also being particularly discriminating. Within the control group a test-retest analysis revealed correlations which, depending on scale and gender, were around .60. It was concluded that the STQ is a valid measure of psychotic traits and that scores on the questionnaire have good long-term stability. The results are discussed against the background, and in support of, a continuity view of psychosis.

Adult↗
PubMed1991

Pulmonary autograft aortic valve replacement: long-term results.

Since 1967, 339 cases of replacement of the aortic valve with the patient's pulmonary valve have been carried out in the National Heart Hospital and the Harley Street Clinic, London. The operation was introduced following the finding of progressive degeneration in previously placed homograft valves. The longest follow-up is 24 years and the cumulative total follow-up is 3,986 patient-years. Overall hospital mortality is 7.4% (25 cases) but with only one death after 1976. Late mortality is 38 patients and actuarial survival is 80% at 20 years. No anticoagulants have been used and there have been no emboli. Bacterial endocarditis occurred in 11 patients. Reoperation was carried out in 33 patients. Freedom from replacement is 85% at 20 years. There is no evidence of calcification or progressive tissue degeneration and the explanted valves show viable tissue. There is also accumulating evidence that the valve can grow in children. The actuarial freedom from all events is 70% at 20 years. With the current low operative risk and absence of progressive degenerative change plus growth prospects, it offers a potentially permanent valve replacement for infants, children, and young adults.

Adolescent↗
PubMed1991

Lack of specificity for antibodies to double stranded DNA found in four commercial kits.

Four commercially available kits (three enzyme linked immunosorbent assays and one modified Farr radioimmunoassay) were compared for their ability to detect specifically autoantibodies to double-stranded DNA (dsDNA) using 66 patient sera. This was assessed by comparing the results of the kits with those from an ELISA specifically measuring antibodies against highly purified dsDNA, single-stranded DNA (ssDNA), native DNA and histones. The RIA and two of the ELISAs seemed equally efficient at detecting antibodies to dsDNA, but all three also detected anti-ssDNA (the RIA being particularly bad for this). The need for highly purified dsDNA was clearly shown. The results obtained with one ELISA did not correlate with any variable investigated in this study. A total of 220 sera were assayed with the IDS RIA, of which 130 were recorded as positive. Of these, 50 sera seemed to contain no identifiable autoantibodies. This very high false positive rate may be due, at least in part, to precipitation of nonspecifically bound labelled DNA.

Antibodies, Antinuclear↗
PubMed1991

Role of tachykinins in hyperpnea-induced bronchovascular hyperpermeability in guinea pigs.

Isocapnic dry gas hyperpnea causes bronchoconstriction in guinea pigs that is mediated by release of tachykinins from airway sensory nerves. Exogenous neuropeptides can induce microvascular leak. Therefore we tested whether dry gas hyperpnea also elicits bronchovascular hyperpermeability by measuring Evans blue-labeled albumin extravasation along the airways of mechanically ventilated guinea pigs. We found that 1) room temperature dry gas hyperpnea increased Evans blue extravasation in extrapulmonary and intrapulmonary airways as a specific consequence of local airway heat/water losses, 2) capsaicin pretreatment ablated the bronchoconstrictor response to dry gas hyperpnea and reduced bronchovascular leak only in intrapulmonary airways, 3) phosphoramidon given to capsaicin-pretreated animals partially restored dry gas hyperpnea-induced bronchoconstriction and increased the vascular hyperpermeability response to hyperpnea in intrapulmonary airways, and 4) propranolol administration had no important effects on any of these airway responses. We conclude that dry gas hyperpnea causes bronchovascular hyperpermeability in guinea pigs. Tachykinins have a dominant role in this response in the intrapulmonary airways, although another mechanism may also contribute to the microvascular leak in the extrapulmonary airways.

Animals↗
PubMed1991

Dunaimycins, a new complex of spiroketal 24-membered macrolides with immunosuppressive activity. I. Taxonomy of the producing organisms, fermentation and antimicrobial activity.

The dunaimycins are a new complex of spiroketal 24-membered macrolides discovered in the fermentation broth of two actinomycetes. Based on taxonomic studies these two cultures, which were isolated from soil, were identified as Streptomyces diastatochromogenes strains AB 1691Q-321 and AB 1711J-452. The dunaimycins possess both immunosuppressive and antimicrobial activity.

Anti-Bacterial Agents↗
PubMed1990

Leucocyte mobilization and release of neutrophil elastase following acute insulin-induced hypoglycaemia in normal humans.

Insulin-induced hypoglycaemia in humans is associated with the rapid mobilization of leucocytes in peripheral blood. The aim of the present study was to determine whether neutrophil activation, manifested in plasma by neutrophil elastase concentration, occurs in response to insulin-induced hypoglycaemia. Acute hypoglycaemia (mean blood glucose 1.3 +/- 0.2 mmol l-1; mean +/- SD) was induced with intravenous insulin in 15 normal human subjects, and provoked an increase in the neutrophil count from 3.4 (range 1.9-6.5) to 10.7 (9.4-16.3) X 10(9) l-1 (p less than 0.001), and in the total leucocyte counts from 5.7 (4.1-8.1) to 12.8 (11.3-18.6) X 10(9) l-1 (p less than 0.001), with associated elevations in plasma neutrophil elastase concentration from 21 (12-34) to 29 (14-70) micrograms l-1 (p less than 0.05), and in total neutrophil elastase concentration from 5.90 (3.13-8.20) to 25.20 (23.00-52.00) mg l-1 (p less than 0.001). As neutrophil elastase is implicated in the development of vascular disease, this rise in response to hypoglycaemia may be of pathological importance in insulin-treated diabetic patients.

Adult↗
PubMed1990

Leucocyte arylsulphatase A activity and subtypes of chronic schizophrenia.

Previous studies have suggested that arylsulphatase A (ASA - the biochemical marker of metachromatic leucodystrophy) deficiency may be present in a sizeable proportion of patients with chronic psychosis. This study surveyed leucocyte ASA activity in a group of chronic psychotic patients and compared ASA activity in 3 subgroups fulfilling Research Diagnostic Criteria for schizophrenia (undifferentiated), paranoid schizophrenia and schizoaffective psychosis. Three of 45 patients had significantly reduced ASA activity but none had metachromatic leucodystrophy. Although ASA levels did not differ significantly between the groups, schizophrenics without a family history of schizophrenia had significantly lower ASA levels than those with. The implications of these findings are discussed.

Adult↗
PubMed1990

Cell populations in the human early pregnancy decidua: natural killer activity and response to interleukin-2 of CD56-positive large granular lymphocytes.

Large granular lymphocytes (LGL) have been shown previously to be the most abundant cell type in the first trimester human decidua. Purified populations of decidual LGL were prepared by flow cytometry of cell dispersions labelled with NKH1 (CD56), an antibody specific for peripheral blood LGL, and the functional properties of CD56-positive cells, CD56-negative and unsorted decidual cells compared. Both CD56-positive cells and unsorted decidual cells have cytotoxic activity against the natural killer (NK) cell target K562 which was weak compared with that of peripheral blood mononuclear cells (PBMC). The CD56-negative cells had no cytotoxic activity against K562. All three decidual cell populations proliferated in response to recombinant human interleukin-2 (rIL-2), but none produced detectable levels of IL-2 in culture. When unsorted decidual cells were cultured for 7 days in rIL-2 the proportion of CD56-positive cells increased and NK activity against K562 was augmented. The NK activity of purified CD56-positive decidual cells was also augmented by culturing in rIL-2. The potential role of decidual LGL in regulating the development of the semi-allogeneic placenta is discussed.

Antigens, Differentiation, T-Lymphocyte↗