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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
PubMed1995

Simple aromatics identified with a NFAT-lacZ transcription assay for the detection of immunosuppressants.

Determination of the mechanism of action of FK506 and cyclosporin A has yielded new molecular targets involved in signal transduction during T cell activation. A common target of FK506 and cyclosporin A is inhibition of activation of the NFAT transcription factor, for which a specific binding region is present in the promoter of the IL-2 gene. A reporter gene assay has been used to screen for agents that interfere with this early step in T cell activation. Simple aromatic compounds that block NFAT-dependent transcription and show in vitro immunosuppressive activity were isolated from the broth and mycelia of two Streptomyces sp. fermentations. The compounds were active at concentrations that were not directly cytotoxic.

Animals↗
PubMed1995

Macquarimicins, microbial metabolites from Micromonospora. I. Discovery, taxonomy, fermentation and biological properties.

A novel series of microbial metabolites were discovered in fermentation broths of two soil isolates. Both cultures were identified as strains of Micromonospora chalcea. Production of the metabolites, named macquarimicins, was monitored by an HPLC assay. A seven-day fermentation yielded 27 mg/liter of macquarimicin A. With MICs of 50 to 100 micrograms/ml, macquarimicin A has only very low activity against strains of Bacteroides and other anaerobes. Macquarimicin B has inhibitory activity against the leukemia cell line P-388.

Animals↗
PubMed1995

Fusacandins A and B; novel antifungal antibiotics of the papulacandin class from Fusarium sambucinum. I. Identity of the producing organism, fermentation and biological activity.

The fuscandins, antifungal agents of the papulacandin class, are produced by a strain of Fusarium sambucinum. Fermentation yielded 60 mg/liter of fusacandin A and minor amounts of fusacandin B. As expected, the fusacandins inhibit (1,3)-beta-glucan synthesis. Fusacandin A is slightly less active than papulacandin B against Candida albicans and, like papulacandin, loses activity in the presence of serum.

Aminoglycosides↗
PubMed1995

Immunohistochemical evaluation of the developing outflow tract in the rat: achieving aortic to mitral fibrous continuity.

OBJECTIVES: To study the development of aortic to mitral fibrous continuity in the normal rat heart. METHODS: The hearts and great vessels of normally developed rat embryos and fetuses aged between 13.25 and 19.75 days of gestation were studied in conjunction with those of newborns aged 2 and 7 days post-partum. Standard histological methods and monoclonal antibodies raised against alpha smooth muscle actin (clone 1A4) and ventricular beta myosin heavy chain were used to demonstrate the ventricular outlets, ventriculo-arterial junction, inner heart curve and aortic infundibulum from the early stages of aortopulmonary septation to attainment of their definitive morphology. RESULTS: The two antibodies demonstrated temporal specificity (actin specificity increased post-partum; myosin specificity maximal during fetal period) in the labelling of their intended structures which correlated with their known developmental profile. Full-thickness fibrous continuity between aortic and mitral valves was not complete until 1 week after birth. After ventricular septation was complete, and thereafter towards the end of fetal life and beyond, separation was maintained by a muscular structure histologically identical to the vestigial netro-aortic root branch of the conduction tissue, a structure known to be derived from the primitive ventricular myocardium within the environs of the inner heart curve. CONCLUSIONS: Ventricular septation (occurring relatively early) and the attainment of fibrous continuity (occurring relatively late in development) are two independent processes. Muscular tissue separating left-sided arterial and atrioventricular valves is not derived from the aortic infundibulum but from the inner heart curve. Persistence of this structure is a feature of normal rat heart development and needs to be recognised when working with rodent-based animal models of congenital heart disease aimed at studying the disruption of the development of the ventricular outflow tracts.

Actins↗
PubMed1994

High-affinity reactions between antigen-specific T-cell receptors and peptides associated with allogeneic and syngeneic major histocompatibility complex class I proteins.

We report here that the intrinsic affinities of the antigen-specific T-cell receptors (TCR) of two unrelated CD8+ T-cell clones for their respective peptide-major histocompatibility complex (MHC) ligands are higher than the values generally thought to prevail for TCR. The TCR of one clone (2C) binds an allogeneic class I MHC protein (Ld) in association with an alpha-ketoglutarate dehydrogenase nonapeptide (QLSPFPFDL, termed QL9) with an intrinsic affinity (intrinsic equilibrium association constant) of 1-2 x 10(7) M-1. The TCR of the other clone (4G3) binds a syngeneic class I MHC protein (Kb) in association with an ovalbumin octapeptide (SIINFEKL, termed pOV8) with an intrinsic affinity of 1.5 x 10(6) M-1. A comparison of the two clones, combined with current views of T-cell repertoire selection in the thymus, leads us to propose that TCR affinities are generally likely to be higher for allogeneic MHC-peptide complexes than for syngeneic MHC-peptide complexes.

Amino Acid Sequence↗
PubMed1994

Conformation and self-association of the peptide hormone substance P: Fourier-transform infrared spectroscopic study.

Fourier-transform i.r. (f.t.i.r.) spectroscopy has been applied to the study of the conformational properties of substance P in aqueous solution. Spectra were obtained in the presence of lipid membranes and Ca2+ to assess the role of these factors in induction of the active conformation of the peptide. In aqueous solution substance P was found to be predominantly unstructured at physiological p2H, where the lack of long-range order is probably related to charge repulsion along the peptide chain. However, substance P aggregated in aqueous solution at p2H > 10.0. Little or no induction of secondary structure was seen on addition of the peptide to negatively charged bilayers, suggesting that interaction with a membrane surface does not play an important role in the stabilization of the active conformation of the peptide. In fact, substance P was found to aggregate in the presence of charged lipids, which would tend to hinder rather than enhance interaction with the receptor. We propose a model for the aggregation of substance P at the bilayer surface, based on our studies of the effect of p2H and lipid/peptide ratio on spectra. Addition of Ca2+ had no effect upon the secondary structure of the peptide or on its interactions with membranes.

Amino Acid Sequence↗
PubMed1994

Isolation and sequence analysis of a cDNA encoding an adenine nucleotide translocator from Plasmodium falciparum.

A cDNA clone encoding the polypeptide for Plasmodium falciparum adenine nucleotide translocator (ANT) was isolated by screening a cDNA library with a 150 base pair fragment of genomic DNA which had been enzymatically amplified using two oligonucleotide primers designed from conserved regions of ANT's from other sources. The deduced amino acid sequence of the P. falciparum cloned insert was highly homologous to ANT of other organisms. Features of the sequence are discussed with reference to the targeting and membrane insertion of ANT. The protein has a molecular mass of 35 kDa as predicted from the 303 amino acids encoded in the open reading frame.

Amino Acid Sequence↗
PubMed1994

Gamekeeper's thumb: a quantitative evaluation of acute surgical repair.

A consecutive series of patients who underwent operation for acute rupture of the ulnar collateral ligament of the thumb during a 3 year period from 1985 to 1988 at the Royal Infirmary of Edinburgh were identified. In total 44 patients sustained this injury of whom 19 were available for clinical assessment. The minimum period of follow-up was 17 months (mean 32 months). All patients were satisfied although six had minor symptoms of discomfort. There were no failures of repair; all repaired ligaments were considered to be clinically taut. A quantitative evaluation demonstrated all had good restoration of pinch grip.

Acute Disease↗
PubMed1994

Revision total knee arthroplasty. Comparison of outcome following primary proximal tibial osteotomy or unicompartmental arthroplasty.

Forty-three patients who had undergone revision total knee arthroplasty following either primary, medial unicondylar arthroplasty (23 patients) or valgus tibial osteotomy (20 patients) for medial compartment osteoarthritis were reviewed. Although the two groups had similar knee scores and range of motion at review, six patients (30%) who had undergone prior tibial osteotomy suffered serious postoperative complications. Of these, four patients had a deep infection. It was felt that several factors were responsible, resulting largely from difficulties in gaining access to the lateral tibial plateau and subsequently causing impairment of wound vascularity and healing. In contrast, those patients undergoing revision of unicondylar prostheses did not experience wound healing problems, but it was noted that in half of the cases, there was significant bone loss from the medial tibial plateau.

Humans↗
PubMed1994

A prospective randomised study of continuous warm versus intermittent cold blood cardioplegia for coronary artery surgery: preliminary report.

Between October 1991 and March 1993, 281 consecutive patients underwent non-emergency isolated coronary artery surgery under the care of one surgeon (A.R.). They were prospectively randomised to receive either intermittent cold (Group I-144 patients) or continuous warm (Group II-137 patients) blood cardioplegia for myocardial protection. There were no significant differences in clinical outcome between the two groups, as judged by operative mortality, rates of peri-operative myocardial infarction, blood loss, need for circulatory support, post-operative neurological deficit, or duration of intensive care or hospital stay. However, sinus rhythm returned spontaneously with greater frequency (91.2% vs 45.8%, P < 0.001) in Group II patients. There was greater transmyocardial oxidative stress in Group I patients, as evidenced by a significant rise in oxidised glutathione in coronary sinus blood on myocardial reperfusion. Also, the serum CKMb isoenzyme level 2 h post-operatively was significantly raised in Group I patients, although this difference had disappeared by the day after surgery. In conclusion this preliminary report suggests that continuous warm blood cardioplegia provides comparable myocardial protection to that achieved with standard hypothermic techniques in patients undergoing coronary artery surgery.

Coronary Angiography↗
PubMed1994

Kinetics and affinity of reactions between an antigen-specific T cell receptor and peptide-MHC complexes.

We show here that the net rate of accumulation of complexes formed by the antigen-specific receptor of T cells (TCR) of a T cell clone with its natural ligand, an octapeptide in association with Ld, a class I protein of the major histocompatibility complex (MHC), approaches the maximal value determined by the affinity of the TCR for this peptide-MHC ligand in 1-2 min, which is well within the lifetime of transient T cell-target cell conjugates. Consistent with this finding, we also found that the widely divergent affinity values (equilibrium constants) of this TCR for six related peptide-MHC complexes correlate well with the extent of specific lysis of target cells bearing various level of these complexes.

Amino Acid Sequence↗
PubMed1994

The hazards of prescribing from serum levels.

Clinical audit at a mental handicap hospital suggested that doses of antiepileptic drugs were being altered in response to suspiciously high or low serum level results. In order to assess the reliability of such results, sequential serum levels for individual patients were examined for consistency. Correlation between results which should have been the same was found to be so low as to call into question the value of drug serum level sampling in this hospital. Investigation of the source of the variability continues. In the meantime, clinical staff are reminded that it is unsafe to make any decision on the basis of a single drug serum level.

Anticonvulsants↗
PubMed1994

Variation in the arterial to end-tidal PCO2 difference during one-lung thoracic anaesthesia.

We have measured the arterial to end-tidal PCO2 difference (PaCO2-PE'CO2) in 22 patients undergoing pulmonary resection in the lateral thoracotomy position during two-lung ventilation (TLV) and after transition to one-lung ventilation (OLV). With OLV for each patient, the practice of correcting the estimate by an initial measurement of (PaCO2-PE'CO2) was evaluated by subtracting the initial (PaCO2-PE'CO2) from subsequent values measured at 10-min intervals. Net (uncorrected) and corrected differences during OLV were analysed using ANOVA. (PaCO2-PE'CO2) values during TLV and OLV were similar: mean (SD) 1.3 (0.6) kPa and 1.2 (0.7) kPa, respectively (ns). Mean (PaCO2-PE'CO2) varied in the range 0.2-2.5 kPa, while maximum (PaCO2-PE'CO2) was 0.3-2.8 kPa. The mean (SD) of 133 pairs of measurements with OLV was 1.1 (0.7) kPa. Even after correction, mean (PaCO2-PE'CO2) varied in the range -0.7 to 0.8 kPa; individual extreme values were from -1.3 to 1.7 kPa. Variation between patients was found to be greater than variation within patients for both net and corrected differences (F ratio = 37.0 and 10.9, respectively), although calculating a corrected difference did reduce variation between patients from a mean square value of 2.44 to 0.61. The wide variation in (PaCO2-PE'CO2) suggests that the accuracy of estimation of PaCO2 by monitoring PE'CO2, although improved by the use of a corrected difference, remains questionable during OLV.

Adult↗
PubMed1994

Polynesian women are also at risk for hyperuricaemia and gout because of a genetic defect in renal urate handling.

The prevalence of asymptomatic hyperuricaemia among Polynesian women (Maoris, Cook Islanders, Samoans, Tongans) was high--44%. This hyperuricaemia resulted from a reduced fractional uric acid clearance (FEur: uric acid clearance factored by creatinine clearance x 100--6.7 +/- 1.5%) compared with the FEur in healthy UK women (12.8 +/- 2.9%). This reduction in FEur was not as great as that in young UK women with familial juvenile hyperuricaemic nephropathy (FJHN: 5.1 +/- 1.5%) and was not associated with impaired renal function. The FEur in the normouricaemic Polynesians (9.7 +/- 1.9%) was also lower than that in healthy UK women (12.8 +/- 2.9%). The reduced FEur in these Polynesian women supports the hypothesis that indigenous Pacific races share a similar genetic defect in renal urate handling to that reported as the basis for the susceptibility to hyperuricaemia in Maori men. Neither alcohol nor hypertension contributed to this. This study also confirmed that, compared with their European counterparts, Polynesian women have a high purine intake and a strong tendency to obesity which increases with age. These factors, together with the reduced FEur, put them at added risk for gout. However, the reduction in FEur was not as great as that reported for the normouricaemic or asymptomatic hyperuricaemic Maori male (4.9 +/- 1.5% and 3.9 +/- 1.4%, respectively), confirming the same sex difference in renal urate handling in adult Polynesians as in caucasians.

Adult↗
PubMed1994

Paediatric road accidents in two health districts.

For a 1-year period from 1 January 1990 all children seen, as a result of road traffic accidents (RTAs), in two accident and emergency departments (A&E), one in Liverpool and one in Chester were studied. Simple data were collected and injury severity scores (ISS) were used to assess injuries. Progress was monitored at 3 months post-injury by a review of hospital case notes. A total of 710 children fulfilled the study criteria in the year with a male:female ratio of 1.7:1. Only 37% of children were accompanied by an adult at the time of their accident. Overall 29% of children in vehicles were restrained and only three of 75 cyclists wore cycle helmets. Most injuries were minor with ISS of less than 9 in 96% of cases. Two children died after admission as a result of severe head injuries. The results were similar to those from other centres but highlight a need for continuing public education on child supervision, safe driving habits and the need for environmental changes.

Accidents, Traffic↗
PubMed1994

Balloon dilatation of the aortic valve after previous surgical valvotomy: immediate and follow up results.

OBJECTIVE: To evaluate the immediate and long-term results of transcatheter balloon dilatation of the aortic valve for restenosis after previous surgical valvotomy. DESIGN: Prospective follow up by clinical examination and cross sectional Doppler echocardiography of all patients fulfilling the above criteria. SETTING: Tertiary paediatric cardiology referral centre. PATIENTS AND METHODS: 22 patients (18 male, 4 female)--median (range) age 157.5 (12-254) months--underwent 25 balloon dilatation procedures at a median of 72 (8-155) months after surgery. The median age at surgical valvotomy was 82.5 (0.5-230) months and the systolic gradient across the aortic valve immediately after surgery was 31 (0-49) mm Hg. The indication for dilatation was a Doppler derived peak instantaneous gradient of > 60 mm Hg with grade 2 or less aortic regurgitation. A single balloon was used, and the median balloon to annulus ratio was 1 (0.9-1). RESULTS: After dilatation the catheter pullback gradient decreased acutely from 55 (35-75) to 30 (0-75) mm Hg (p < 0.01) and the Doppler gradient from 74 (52-92) to 40.5 (30-96) mm Hg (p < 0.01). In three patients who underwent a second dilatation of the aortic valve eight months after the first procedure, the pullback gradient decreased from 50 (50-60) to 15 (15-16) mm Hg. Aortic regurgitation grade increased from 1 (0-2) to 2 (1-3); only one patient had grade 3 regurgitation. Over a median follow up of 33 (2-67) months seven patients had aortic valve replacement for recurrent stenosis (six patients) or severe regurgitation (one patient with grade 3 regurgitation after dilatation, who had partial detachment of one of the valve leaflets). There was no significant difference for the pullback gradient (median of 19 v 32.5 mm Hg), Doppler gradient 24 hours after dilatation (33.5 v 50.5 mm Hg; p = 0.03), or the duration of follow up (27.5 v 18 months) between the 12 patients who did not require further dilatation or surgery and the 10 patients who did. CONCLUSIONS: Balloon dilatation of the aortic valve is a safe and feasible option for palliation of restenosis after surgical valvotomy for congenital aortic valve stenosis. In many patients, however, stenosis progressed and a further intervention was required.

Adolescent↗