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Biomedical subjects

S John

Publications and source records attributed to S John.

At least 145 records · Page 8Linked to original sources

Quantum dynamics as a stochastic process.

The quantum Liouville equation is solved in the Wigner representation using generalized Monte Carlo techniques. For small increments of time, the solution is represented as a sequential classical evolution in phase space followed by a quantum "jump" distribution in momentum space, with the latter simulated via a stochastic method. Extending the work initiated by John and Remler [Ann Phys. (N.Y.) 180, 152 (1987)] the technique is developed and validated for higher dimensions. Also, an alternative algorithm is developed and applied to study motion of a quantum system in an anharmonic quartic potential well, with significantly improved results.

Algorithms↗

Monitoring drug use in palliative care.

A computerized system for monitoring drug use which makes use of the British National Formulary (BNF) drug categories and a departmental formulary (DF) has been developed. Data entry takes less than one week of secretarial time per annum. Details of drug use in 385 patients three weeks after referral to a National Health Service palliative care unit over five years form the basis of this report. The median number of drugs per patient was five, with a maximum of 11; 97% of the drugs were from the DF. Analgesics were the commonest category of drugs used. The 10 most commonly used drugs included three analgesics (morphine, co-proxamol, flurbiprofen), two laxatives (co-danthrusate, lactulose), dexamethasone, metoclopramide, ranitidine, temazepam and amitriptyline/dothiepin. Seventeen per cent of patients received two preparations from the same second level BNF category (analgesics excluded). The concurrence was questionable in about half of these, and mostly related to the use of laxatives or to hypnotics and anxiolytics. Several unexpected inclusions in the top 10 drugs illustrate the need for quantification rather than pontification about drug use in palliative care. Examination of duplicate prescribing provides a forum for examining ways of simplifying drug regimens.

Adult↗

Correlation of serum prostate specific antigen levels and bone scintigraphy in carcinoma prostate.

Serum prostate specific antigen (PSA) has been suggested as an accurate means of monitoring prostate cancer. An analysis of PSA levels and bone scan findings was carried out in a heterogeneous group of patients with a view to determine whether PSA can accurately predict bone metastases in carcinoma prostate. Of the 48 patients studied, all 10 untreated cases had elevated PSA levels, eight having bone metastases. In 29 cases on follow-up after treatment of the primary, 10 out of 11 cases with normal PSA had a negative bone scan. In the nine who received hormonal therapy, the PSA levels were generally lower than others in the study group. Two out of four with normal PSA had bone metastases. In 26 cases with positive bone scans, 23 had elevated PSA levels (mean 109.9 ng ml-1). Among 22 patients who had normal bone scans, all 10 with high PSA were found to have soft tissue disease which could explain the elevated PSA. In those with normal PSA, 12 out of 15 patients had negative scans. PSA has fairly high sensitivity (86.5%) and negative predictive value (80%). But it suffers from low specificity (54.5%) and low positive predictive value (69.7%) for bone metastases. In an untreated patient with elevated PSA, a bone scan may be required to exclude bone metastases, whereas during follow-up after treatment, a normal PSA level may obviate a "routine" bone scan.

Adenocarcinoma↗

Familial nanophthalmos: management and complications.

Nanophthalmos is a rare form of congenital hypermetropia, in which, the individual is at a high risk of developing angle-closure glaucoma. We report a family of nanophthalmos affecting a brother and sister, as confirmed by biometry. Genetic analysis revealed an autosomal recessive mode of inheritance. The sister developed angle-closure glaucoma, which was refractory to medical and laser therapy. She underwent surgical interventions which resulted in complications. The clinical presentation, management, and complications encountered are discussed.

Adult↗

Serum circulating ICAM-1 levels are not useful to indicate active vasculitis or early renal allograft rejection.

During inflammation, activated vascular endothelial cells and other cell types express various adhesion molecules which facilitate binding of circulating leukocytes. Serum concentration of circulating adhesion molecule ICAM-1 (c-ICAM-1) is supposed to reflect the degree of this activation. In order to evaluate the usefulness of c-ICAM-1 serum levels for assessment of disease activity in various vasculitic disorders, we examined 23 patients with systemic lupus erythematosus (SLE, n = 9). Wegener's granulomatosis (WG, n = 6), Goodpasture syndrome (GP, n = 6) and microscopic polyarteritis (MP, n = 2). Disease activity was defined by clinical criteria and by conventional laboratory data. Circulating ICAM-1 concentrations were measured during periods of active clinical vasculitis and on clinical remission. In a second part of the study, we examined whether or not c-ICAM-1 might be helpful in diagnosing acute allograft rejection early after kidney transplantation. After cadaveric kidney transplantation thirteen patients were included. Serum probes were gathered firstly after transplantation, secondly at time of histologically proven allograft rejection and finally after successful anti-rejection therapy and restored transplant function. c-ICAM-1 levels in healthy volunteers (n = 10) were 270 +/- 47 ng/ml (mean +/- SD). Patients with active vasculitis had mean serum levels of 509 +/- 71 ng/ml (SLE), 594 +/- 118 ng/ml (WG), 472 +/- 126 ng/ml (GP) and 498 ng/ml (MP) (mean +/- SD). In clinical remission, mean serum concentrations were found to be 500 +/- 99 ng/ml (SLE), 597 +/- 84 ng/ml (WG), 782 +/- 163 ng/ml (GP) and 594 ng/ml (MP) (mean +/- SD).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Functional analysis of a growth factor-responsive transcription factor complex.

Serum response factor (SRF) forms a ternary complex at the c-fos serum response element (SRE) with an accessory factor, Elk-1. We constructed altered-binding specificity derivatives of SRF and Elk-1 that form a ternary complex at a mutated, inactive SRE; like Elk-1, the Elk-1 variant only binds its target as part of a ternary complex with SRF. Simultaneous expression of these SRF and Elk-1 derivatives restores serum-regulated activity to the mutated SRE in transfected cells. Efficient transcriptional activation is dependent on the regulated phosphorylation of Elk-1 C-terminal MAP kinase sites and requires the C-terminal sequences of SRF as well as SRF sequences that mediate ternary complex formation. These experiments provide direct evidence that SRF and Elk-1 functionally cooperate in the ternary complex at the SRE to regulate transcription.

3T3 Cells↗

Effect of locus coeruleus lesion on c-fos expression in the cerebral cortex caused by yohimbine injection or stress.

The injection of the alpha-2 adrenoceptor antagonist, yohimbine, has been shown to increase c-fos immunoreactivity in the rat cerebral cortex. To determine the extent to which this response is mediated by the central noradrenergic system, the present studies examined it in rats previously given unilateral 6-OHDA lesions of the locus coeruleus. The lesions were found to produce a significant attenuation of the response. A similar effect on the c-fos immunoreactive response to restraint stress was found. It is concluded that the noradrenergic system plays a necessary role in the above c-fos responses in the cortex to yohimbine and to stress. The c-fos protein therefore appears to be involved in the effects of noradrenergic neurotransmission in the CNS.

Animals↗

Disposition and orientation of ductin (DCCD-reactive vacuolar H(+)-ATPase subunit) in mammalian membrane complexes.

The disposition and orientation of mouse ductin (the subunit c of the vacuolar H(+)-ATPase) in gap junctions has been examined. Like the Nephrops norvegicus (arthropod) form, mouse ductin in the intact junctional structure is resistant to high levels of nonspecific proteinase, suggesting that it is for the most part buried in the bilayer. Antisera to an octapeptide near the N-terminus cross-react with ductins in gap junction preparations from four different mouse tissues, from chicken and Xenopus laevis liver, and from N. norvegicus hepatopancreas. The antisera and antibodies, affinity purified against the octapeptide, agglutinate isolated gap junctions, suggesting that the N-terminus is located on the exposed surface, equivalent to the cytoplasmic face of an intercellular gap junction. The antibodies also block dye coupling when injected into cells in culture, confirming the cytoplasmic location of the epitope. The lipophylic reagent dicylohexyl carbodiimide (DCCD), which targets carboxyl groups within the membrane and selectively reacts with ductin in N. norvegicus gap junction preparations, rapidly inhibits junctional communication. Bafilomycin A1, which inhibits V-ATPase and stops vacuolar acidification, does not affect dye coupling, showing that the inhibition seen with antibodies and DCCD is not an indirect consequence of their action on the ductin of V-ATPase. Consistent with this interpretation the anti-peptide antibodies do not bind to intact chromaffin granules or inhibit their V-ATPase activity, but do bind to osmotically disrupted granule membrane. This suggests that ductin has an orientation (N-terminus pointing away from the cytoplasm) in the vacuolar membrane opposite to that in the gap junction membrane.

Amino Acid Sequence↗

Transducer related Enterobacter cloacae sepsis in post-operative cardiothoracic patients.

The use of intra-arterial pressure monitoring devices in patients undergoing major cardiac surgery is on the increase. Here we document an outbreak of Enterobacter cloacae septicaemia among seven post-operative cardiothoracic patients. Detailed investigations revealed the source of this nosocomial problem to be contaminated transducer heads. The need to follow strict aseptic measures in handling intra-arterial devices is emphasized, in order to minimize the morbidity and mortality in otherwise low-risk post-operative patients.

Cardiac Surgical Procedures↗

Geometric model for nuclear absorption from microscopic theory.

A parameter-free geometric model for nuclear absorption is derived from microscopic theory. The expression for the absorption cross section in the eikonal approximation taken in integral form is separated into a geometric contribution, described by an energy-dependent effective radius, and two surface terms which are shown to cancel in an asymptotic series expansion. For collisions of light nuclei, an expression for the effective radius is derived using harmonic-oscillator nuclear density functions. A direct extension to heavy nuclei with Woods-Saxon densities is made by identifying the equivalent half density radius for the harmonic-oscillator functions. Coulomb corrections are incorporated and a simplified geometric form of the Bradt-Peters type obtained. Results spanning the energy range of 1 MeV/nucleon to 1 GeV/nucleon are presented. Good agreement with experimental results are obtained.

Elementary Particles↗

Characterization of the human interleukin-2 receptor beta-chain gene promoter: regulation of promoter activity by ets gene products.

The interleukin-2 receptor (IL-2R) beta chain (IL-2R beta) is an essential signaling component of high- and intermediate-affinity IL-2Rs. Our laboratory previously reported that a DNA fragment containing 857 bp of 5'-flanking sequence of the human IL-2R beta gene exhibited promoter activity. We have now further characterized the promoter and delineated cis-acting regulatory regions. The region downstream of -363 is critical for basal and phorbol myristate acetate-inducible IL-2R beta promoter activity and contains at least three enhancer-like regions. Among them, the -56 to -34 enhancer was the most potent and had high-level activity in two T-cell lines but not in nonlymphoid HeLaS3 and MG63 cells. This enhancer contains a GGAA Ets binding site which bound two Ets family proteins, Ets-1 and GA-binding protein in vitro. Mutation of the Ets motif strongly diminished both promoter and enhancer activities. We conclude that this Ets binding site plays a key role in regulating basal and phorbol myristate acetate-inducible IL-2R beta promoter activity and may also contribute to tissue-specific expression of the IL-2R beta gene.

Amino Acid Sequence↗

Late-onset Lafora's disease with typical intraneuronal inclusions.

We describe a patient with progressive myoclonus epilepsy (late-onset Lafora's disease). Onset was in early adult life, and death was at age fifty-four. The initial symptoms were epileptic seizures and progressive dementia, with later occurrence of myoclonus. Lafora bodies were ubiquitous and in neuronal perikarya in many areas. Dust-like granular bodies predominated in the neuropil of cerebral cortex, substantia nigra, and striatum. Abnormal deposits were also found in the myocardium.

Brain↗

Tetralogy of Fallot: intracardiac repair in 840 subjects.

Since 1967, when the first intracardiac repair was performed in this centre, until 1991, 840 symptomatic subjects with tetralogy of Fallot have undergone corrective surgery. Cardiac catheterization and angiocardiography were carried out in all patients. Cardinal findings on the clinical status of these subjects are outlined. A substantial number of patients (244; 29.0%) were > 15 years of age. Historically, a transannular pericardial gusset has been utilized in 578 (68.8%), and in 423 (93.0%) during the past decade. The incidence of residual interventricular septal defects has been 0.68% and occurrence of complete heart block after surgery 0.4%. Death occurred in 86 patients (10.2%) within 30 days of operation and later in 40 subjects (4.8%). Long-term results have been excellent with good haemodynamic status in > 90% of subjects in the follow-up period. Associated features including absent pulmonary valve, absent left pulmonary artery, and previous palliative shunts did not alter the outcome; however, a raised haematocrit (> 0.65) was associated with an increased mortality rate.

Adolescent↗