Search PubMed⌕ Search

Biomedical subjects

M Jackson

Publications and source records attributed to M Jackson.

At least 73 records · Page 4Linked to original sources
PubMed1999

Inactivation of the antigen 85C gene profoundly affects the mycolate content and alters the permeability of the Mycobacterium tuberculosis cell envelope.

The antigen 85 complex of Mycobacterium tuberculosis consists of three abundantly secreted proteins. The recent characterization of a mycoloyltransferase activity associated in vitro with each of these antigens suggested that they are potentially important for the building of the unusual cell envelope of mycobacteria. To define the physiological role of these proteins, the gene coding for antigen 85C was inactivated by transposon mutagenesis. The resulting mutant was shown to transfer 40% fewer mycolates to the cell wall with no change in the types of mycolates esterifying arabinogalactan or in the composition of non-covalently linked mycolates. As a consequence, the diffusion of the hydrophobic chenodeoxycholate and the hydrophilic glycerol, but not that of isoniazid, was found to be much faster through the cell envelope of the mutant than that of the parent strain. Taken together, these data demonstrate that: (i) antigen 85C is involved directly or indirectly in the transfer of mycolates onto the cell wall of the whole bacterium; (ii) the enzyme is not specific for a given type of mycolate; and (iii) the cell wall-linked mycolate layer may represent a barrier for the diffusion of small hydrophobic and hydrophilic molecules.

Acyltransferases↗
PubMed1999

Infrared spectra of basal cell carcinomas are distinct from non-tumor-bearing skin components.

Infrared spectroscopy, by probing the molecular vibration of chemical bonds, directly indicates tissue biochemistry. An expanding body of literature suggests that infrared spectra distinguish diseased from normal tissue. The authors used infrared spectroscopy to examine basal cell carcinoma to explore distinctive characteristics of basal cell carcinoma versus normal skin samples and other skin neoplasms. Spectra of epidermis, tumor, follicle sheath, and dermis were acquired from unstained frozen sections, and analyzed qualitatively, by t-tests and by linear discriminant analyses. Dermal spectra were significantly different from the other skin components mainly due to absorptions from collagen in dermis. Spectra of normal epidermis and basal cell carcinoma were significantly different by virtue of subtle differences in protein structure and nucleic acid content. Linear discriminant analysis characterized spectra as arising from basal cell carcinoma, epidermis, or follicle sheath with 98.7% accuracy. Use of linear discriminant analysis accurately classified spectra as arising from epidermis overlying basal cell carcinoma versus epidermis overlying nontumor-bearing skin in 98.0% of cases. Spectra of basal cell carcinoma, squamous cell carcinoma, nevi, and malignant melanoma were qualitatively similar. Distinction of basal cell carcinoma, squamous cell carcinoma, and melanocytic lesions by linear discriminant analyses, however, was 93.5% accurate. Therefore, spectral separation of abnormal versus normal tissue was achieved with high sensitivity and specificity, which points to infrared spectroscopy as a potentially useful screening tool for cutaneous neoplasia.

Basal Cell Carcinoma↗
PubMed1999

Classification of breast tumors by grade and steroid receptor status using pattern recognition analysis of infrared spectra.

Infrared (IR) spectroscopy applied to tissue sections yields complex spectra that provide a molecular fingerprint of the tissue. We have studied a cohort of 77 breast tumors by IR spectroscopy to develop an objective method for the assignment of grade of breast tumors. Although the major variations between spectra from different tumors were in absorptions arising from triglycerides (adipose tissue) and collagen, subtle changes in spectra could be detected that were independent of cellularity and tissue composition. Using a specific multivariate pattern recognition strategy to associate these changes in spectra with different tumor grades, we then were able to accurately reclassify tumors by grade (87% accuracy; kappa = 0.835). A similar approach allowed classification of steroid receptor status (93% accuracy; kappa = 0.852). We conclude that IR spectroscopy may have clinical utility in the objective assignment of breast tumor grade.

Breast Neoplasms↗
PubMed1999

Psoriatic keratinocytes show reduced IRF-1 and STAT-1alpha activation in response to gamma-IFN.

Psoriasis is a chronic inflammatory dermatosis characterized by hyperproliferative keratinocytes (KC). The skin lesions are infiltrated by T cells, which secrete gamma interferon (gamma-IFN) and are believed to be necessary to maintain the psoriatic phenotype. In normal KC, gamma-IFN is a potent inhibitor of proliferation, but proliferation of KC persists in psoriatic plaques despite the presence of gamma-IFN. Immunostaining of interferon regulatory factor-1 (IRF-1) revealed that IRF-1 was localized to the basal cells of the epidermis in normal and in nonlesional psoriatic skin, but was suprabasal or completely absent in lesional psoriatic skin. This finding led to the hypothesis that abnormal signaling in the gamma-IFN pathway may occur in psoriatic KC. To test this hypothesis, we measured activation of IRF-1 and signal transducer and activator of transcription (STAT)-1alpha transcription factors in KC after stimulation with gamma-IFN. Primary cultures of KC from normal and nonlesional psoriatic skin were stimulated with gamma-IFN and subsequent transcription factor activation was measured by electrophoretic mobility shift assay. Psoriatic KC showed a reduced induction of IRF-1 and STAT-1alpha activation after stimulation with gamma-IFN, compared with normal KC. Reduced activation of IRF-1 and STAT-1alpha in response to gamma-IFN indicates a fundamental defect in the growth and differentiation control of psoriatic KC in the absence of the influence of other cell types.

Adult↗
PubMed1999

Persistence and protective efficacy of a Mycobacterium tuberculosis auxotroph vaccine.

New vaccines against tuberculosis are urgently required because of the impressive incidence of this disease worldwide and the highly variable protective efficacy of the current vaccine. The possibility of creating new live vaccines by the rational attenuation of strains from the Mycobacterium tuberculosis complex was investigated. Two auxotrophic mutants of M. tuberculosis and M. bovis BCG were constructed by disruption of one of their purine biosynthetic genes. These mutants appeared unable to multiply in vitro within mouse bone-marrow derived macrophages. They were also attenuated in vivo in the mouse and guinea pig animal models. In guinea pigs, the two mutants induced strong delayed-type hypersensitivity response to purified protein derivative. In a preliminary experiment, the two mutants were compared to the BCG vaccine for their protective efficacy in a challenge against aerosolized virulent M. tuberculosis in the guinea pig model. Both mutants conferred some level of protection. These experiments demonstrate that the rational attenuation of M. tuberculosis could lead to the design of new candidate live vaccines against tuberculosis.

Animals↗
PubMed1999

Association of the APOE epsilon4 allele with disease activity in multiple sclerosis.

OBJECTIVES: Allelic variants of the APOE gene are known to influence the course of many neurological diseases and there is increasing evidence that apolipoprotein E (APOE) is a pivotal component in reinnervation and dendritic remodelling after neuronal injury. Previous studies did not show significant differences in the APOE allele frequencies in multiple sclerosis compared with controls but did not examine for correlation with disease severity. This study explores the relation of APOE genotypes with the disease severity. METHODS: Ninety five patients with multiple sclerosis were studied. Age of onset, type, and activity of the disease were recorded prospectively and genotyping was performed according to standard protocols. RESULTS: APOE allele frequencies of the group as a whole, the relapsing group, or the primary progressive group were not significantly different from those reported from matched historical controls. The epsilon4 allele was found to be more common in patients with a more aggressive type of multiple sclerosis (odds ratio=2.95, p=0.03). CONCLUSIONS: Although APOE does not seem to be implicated in the early pathogenesis of the disease, patients possessing the epsilon4 allele might have a reduced capacity for neuronal remodelling after relapses.

Adult↗
PubMed1999

Leucocyte-depleted cardioplegia does not reduce reperfusion injury in hypothermic coronary artery bypass surgery.

This study investigated the effects of leucocyte-depleted cardioplegia on postreperfusion oxidative stress and myocardial injury in elective hypothermic coronary artery bypass surgery. Forty patients were randomized to receive either cardioplegia with leucocytes depleted by an in-line Pall BC1B filter, or blood cardioplegia without leucocyte depletion. Transmyocardial oxidative stress was assessed by oxidized glutathione measurements in samples taken simultaneously from the coronary sinus and aortic root, and myocardial injury by postoperative CKMB and troponin-T measurements. The BC1B filters reduced numbers of cardioplegia leucocytes by a mean of 90.7%. Both patient groups demonstrated significant increases (p < 0.001) in transcardiac oxidized glutathione gradients after crossclamp release. No significant differences were found between the groups for postreperfusion oxidized glutathione gradients, postoperative levels of CKMB or troponin-T, or in the frequency of perioperative and postoperative complications. These results suggest that leucocyte-depleted cardioplegia does not significantly improve myocardial protection in patients undergoing elective coronary artery bypass surgery.

Aged↗
PubMed1999

Modern radiotherapy. Does the GP have a role?

BACKGROUND: Radiotherapy has advanced dramatically in the last 20 years. OBJECTIVE: This article describes the basic biology of radiotherapy, which has led to models being produced that predict for outcome and side effects. Technical innovations allow for better tumour localisation and dose delivery. DISCUSSION: Radiotherapy has an important role in the multi-disciplinary care of the cancer patient and early involvement of a radiation oncologist may help optimise an individual patient's care.

Family Practice↗
PubMed1998

Ethyl-substituted erythromycin derivatives produced by directed metabolic engineering.

A previously unknown chemical structure, 6-desmethyl-6-ethylerythromycin A (6-ethylErA), was produced through directed genetic manipulation of the erythromycin (Er)-producing organism Saccharopolyspora erythraea. In an attempt to replace the methyl side chain at the C-6 position of the Er polyketide backbone with an ethyl moiety, the methylmalonate-specific acyltransferase (AT) domain of the Er polyketide synthase was replaced with an ethylmalonate-specific AT domain from the polyketide synthase involved in the synthesis of the 16-member macrolide niddamycin. The genetically altered strain was found to produce ErA, however, and not the ethyl-substituted derivative. When the strain was provided with precursors of ethylmalonate, a small quantity of a macrolide with the mass of 6-ethylErA was produced in addition to ErA. Because substrate for the heterologous AT seemed to be limiting, crotonyl-CoA reductase, a primary metabolic enzyme involved in butyryl-CoA production in streptomycetes, was expressed in the strain. The primary macrolide produced by the reengineered strain was 6-ethylErA.

Acyl Coenzyme A↗
PubMed1998

A genetically engineered strain of Saccharopolyspora erythraea that produces 6,12-dideoxyerythromycin A as the major fermentation product.

The erythromycin producer, Saccharopolyspora erythraea ER720, was genetically engineered to produce 6,12-dideoxyerythromycin A, a novel erythromycin derivative, as the major macrolide in the fermentation broth. Inspection of the biosynthetic pathway for erythromycin would suggest that production of this compound could be achieved simply through the disruption of two genes, that encoding the erythromycin C-6 hydroxylase (eryF) and that encoding the erythromycin C-12 hydroxylase (eryK). The double mutant, however, was found to produce a mixture of 6,12-dideoxyerythromycin A and the precursor, 6-deoxyerythromycin D. Complete conversion to the desired product (to the limit of detection by TLC) was achieved by inserting an additional copy of the eryG gene, encoding the erythromycin 3"-O-methyltransferase and driven by the ermE* promoter, into the S. erythraea chromosome.

Bacterial Proteins↗
PubMed1998

Diagnosis and management of fetal nuchal translucency.

Fetal nuchal translucency can be measured in most pregnant women in the first and early second trimester. The size of translucency varies slightly with gestational age and crown rump length and is independent of maternal age. Most authors have used a nuchal thickness of > or = 2.5 mm or > or = 3 mm to define abnormal, although some have suggested that the normal variation with gestation requires that different thresholds be used at different gestational ages. The accuracy of nuchal translucency measurement varies between examiners and between patients, likely in relation to examiner skill and image resolution. The small size of a nuchal translucency, less than 3 mm in most cases, probably approximates the threshold of normal interexaminer and intraexaminer variability. The presence of a thickened nuchal translucency is associated with chromosomal abnormality and perhaps with structural abnormality even when the karyotype is normal. Because of the reported variations in the populations studied, the methods used, and the results of screening, it is inappropriate at this time to assign a numeric risk to any individual patient with this finding. However, in both high-risk and low-risk groups, the positive predictive value appears to be high enough that patients with increased nuchal translucency should be counseled by their obstetrician and prenatal diagnostic testing should be offered. Because early genetic diagnosis by CVS has a substantially higher procedure-associated loss rate than amniocentesis in the second trimester, many patients may elect to wait for chromosomal testing. If so, disappearance of nuchal thickening should not be taken as reassurance. As a screening test to be widely applied to a general or low-risk population, the utility of fetal nuchal translucency measurement is uncertain. The reported sensitivity for identification of trisomy 21 has ranged from about 40% to 80%, and the sensitivity for identification of other aneuploidies may be lower than for Down's syndrome. From a cost-risk-benefit standpoint, universal first-trimester ultrasound screening has not been appropriately compared with standard risk assessment using maternal age and multiple-marker serum screening, with amniocentesis as the predominant diagnostic method. Also, the issues of availability and reimbursement have not been addressed. Currently, measurement of nuchal translucency is not a substitute for the standard of obstetrical care, which is to offer multiple-marker serum screening to every pregnant woman at 15 to 20 weeks. Similarly, it is inappropriate to substitute nuchal translucency measurement for genetic counseling and CVS or amniocentesis in women above 35 years of age or those with a significant positive history. Finally, the data are not clear as to whether a normal nuchal translucency decreases the likelihood of chromosomal abnormality in a high-risk population, and such women should not be discouraged from invasive testing because of a normal first-trimester ultrasound study. The data supporting the association between thickened nuchal transluency and chromosomal abnormality are compelling, but further study is needed before adopting routine nuchal translucency screening. Combining first-trimester ultrasonography with early serum screening is currently being investigated and may ultimately prove to be the most efficient means of screening for chromosomal anomaly.

Aneuploidy↗
PubMed1998

Use of the fixed mandibular implant in oral cancer patients: a retrospective study.

PURPOSE: A retrospective review of the fixed mandibular implant (FMI) in oral cancer patients is presented. Success of the device and associated complications are discussed. PATIENTS AND METHODS: Eighteen oral cancer patients with an FMI were identified. All were treated at a single institution. Information was obtained from medical records, radiographs, and recall examination. Demographic data, surgical history, prosthesis design, and functional data were analyzed. Results were statistically compared with outcome data for the FMI in noncancer controls. RESULTS: The average patient age was 64 years. Seventeen of the 18 patients had squamous cell carcinoma, most being T3 or T4 lesions at diagnosis. Four of 18 patients received radiation therapy (XRT) followed by resection, 11 had resection followed by XRT, two had XRT alone, and one had surgery alone. The average XRT dose to the mandible was 65.4 Gy. Two of the patients received hyperbaric oxygen (HBO). Sixteen of the implants had been loaded and followed an average of 16.4 months. Early complications included soft tissue overgrowth around pins (4 of 18); tongue ulceration (2 of 18), and intraoral wound dehiscence (2 of 18). Late complications included fistula formation (3 of 18); submental erythema (2 of 18), and persistent tissue overgrowth around pins (1 of 19). No complications required removal of the implant. Only the rate of fistula formation was statistically greater than in controls (P = .005). Average time between FMI placement and prosthesis delivery was 3.6 months. Fourteen of the 16 patients with a prosthesis reported improved ability to eat solid foods and improved articulation. All 16 patients reported improved aesthetics and increased comfort in social settings. CONCLUSIONS: The FMI is a valuable device for dental rehabilitation in oral cancer patients. Success was shown in radiated patients. The complication rate is acceptable, and stability was shown over the follow-up period. Rapid rehabilitation and functional and aesthetic improvements were also reported.

Aged↗
PubMed1998

An evaluation of the use of concentrators for domiciliary oxygen supply for less than 8 h day-1.

Since their introduction in 1985, oxygen concentrators have only been recommended when domiciliary oxygen is used for over 8 h day-1. Subsequent changes in the prices of oxygen merit a reappraisal of the prescribing of concentrators and cylinders when oxygen is used for less than 8 h day-1. Twenty-six patients in two health districts who used oxygen for less than 8 h day-1 completed a crossover study in which each group received oxygen from each source for consecutive 3-month periods. The patients were visited at home before and during the study, and on each visit they completed a questionnaire asking about their use of oxygen, how acceptable they found the two sources and about several dimensions of their quality of life. The theoretical minimum cost of cylinder supply, the actual cost of cylinder supply and the average concentrator costs were assessed. The patients found the concentrators to be more acceptable, more useful and less obtrusive than cylinders. They used more oxygen in more rooms of the home during treatment with concentrators, and there were improvements in the quality-of-life measurements. The costing information showed that, both in theory and in practice, oxygen concentrators are cheaper than cylinders when oxygen is used for more than about 1.4 h day-1. These results suggest that the provisions for the supply of domiciliary oxygen should be reviewed and that concentrators should be recommended for patients who use more than around 1.4 h day-1.

Aged↗
PubMed1998

Myocardial ischaemia after coronary artery bypass grafting: early vs late extubation.

The technique of early extubation after coronary artery bypass grafting is increasing in popularity, but its safety and effect on myocardial ischaemia remain to be established. In a randomized, prospective study, patients undergoing routine elective coronary artery bypass grafting were managed with either early or late tracheal extubation. The incidence and severity of electrocardiographic myocardial ischaemia were compared. Data were analysed from 85 patients (43 early extubation; 42 late extubation). Median time to extubation was 110 min in the early extubation patients and 757 min in the late extubation patients. After correction for randomization bias, there were no significant differences between groups in ischaemic burden, maximal ST-segment deviation, incidence of ischaemia and area under the ST deviation-time curve (integral of ST deviation and time). Similarly, there were no differences between groups in postoperative creatine kinase MB-isoenzyme concentrations and duration of stay in the ICU or hospital. Therefore, this study provides evidence for the safety of early extubation after routine coronary artery bypass grafting.

Adult↗
PubMed1998

Comparison of the effects of sevoflurane and isoflurane on arterial oxygenation during one lung ventilation.

We have compared the effects of sevoflurane and isoflurane on arterial oxygenation, heart rate and mean arterial pressure during one lung anaesthesia in a prospective, crossover study. We studied 28 patients undergoing oesophagogastrectomy, allocated alternatively to one of two groups. Patients in group I/S (n = 14) received 1 MAC (1.1%) of isoflurane in oxygen from induction until the end of 30 min of open chest one lung ventilation (OLV) in the lateral position. This was followed by 1 MAC (2.1%) of sevoflurane in oxygen for the next 30 min of OLV. Patients in group S/I (n = 14) received the two anaesthetic agents in the reverse order. We found no significant difference in arterial oxygenation, heart rate or mean arterial pressure between the two potent inhalation agents. In the subgroup of patients with pulmonary artery catheters (n = 12), we found a significant increase (P < 0.05) in derived shunt during sevoflurane anaesthesia. There was no significant difference in mixed venous saturation and cardiac output. We conclude that during one lung ventilation, the choice between sevoflurane and isoflurane did not significantly influence arterial oxygenation.

Aged↗
PubMed1998

'It begins with the goose and ends with the goose': medical, legal, and lay understandings of imbecility in Ingram v Wyatt, 1824-1832.

A number of historians have recently suggested that we need to get out of the asylum if we are to fully understand attitudes to insanity in the nineteenth century. Arguing that accounts of the medicalization of madness have ignored the importance of non-medical attitudes to lunacy and idiocy, recent studies have stressed the need to explore family attitudes and responses in more detail. Unfortunately, efforts to escape the asylum have to some extent been hampered by a persistent reliance on institutional records. This institutional dependence is understandable: certificates of insanity, reception orders, case-books, and asylum registers, together with published documents, constitute the major record of historical constructions of the lunatic and idiotic mind. However, there may be more resourceful ways of exploring both medical and non-medical attitudes to idiocy. In this paper, I want to use the records from a contested will case, Ingram v Wyatt, to demonstrate that records from the ecclesiastical courts can provide access to a domain where the definitions and meanings of idiocy and imbecility were routinely considered by lawyers, lay witnesses, judges, and doctors. I shall argue that such cases constitute a fruitful site for excavating lay, professional legal, and medical attitudes to imbecility, for exploring the complex relationship between medical and non-medical understandings of capacity, and for situating those understandings within the context of professional developments in law and medicine and contemporary concerns about inheritance.

History, 19th Century↗
PubMed1998

Catechol-O-methyltransferase inhibition with tolcapone reduces the "wearing off" phenomenon and levodopa requirements in fluctuating parkinsonian patients.

BACKGROUND: More than 50% of patients with Parkinson's disease develop motor response fluctuations (the 'wearing off" phenomenon) after more than five years of levodopa therapy. Inhibition of catechol-O-methyltransferase by tolcapone has been shown to increase levodopa bioavailability and plasma elimination half life, thereby prolonging the efficacy of levodopa. OBJECTIVES: The primary objective was to evaluate the efficacy of tolcapone in reducing "wearing off" in levodopa treated, fluctuating parkinsonian patients. Secondary objectives included assessment of reduction in levodopa requirements, improvement in patients' clinical status, duration of improvements, and tolerability of tolcapone. METHODS: In this multicentre, randomised, double blind, placebo controlled trial, 58 patients received placebo, 60 received 100 mg tolcapone three times daily (tid), and 59 received 200 mg tolcapone tid, in addition to levodopa/benserazide. RESULTS: After three months with 200 mg tolcapone tid, "off" time decreased by 26.2% of the baseline value, "on" time increased by 20.6% (p < 0.01 vs. placebo), and the mean total daily levodopa dose decreased by 122 mg from the baseline dose of 676 mg (p < 0.01). These responses were maintained up to nine months. With 100 mg tolcapone tid, "off" time decreased by 31.5% (p < 0.05), "on" time increased by 21.3% (p < 0.01), and the mean total daily levodopa dose decreased by 109 mg from the baseline dose of 668 mg (p < 0.05). With 200 mg tolcapone tid, unified Parkinson's disease rating scale motor and total scores were significantly reduced, and quality of life (sickness impact profile) scores were significantly improved. Both dosages were well tolerated. Dyskinesia was the most often reported levodopa induced adverse event. Diarrhoea was the most often reported non-dopaminergic adverse event and the most frequent reason for withdrawal from the study: four patients in the 100 mg tolcapone tid group and six in the 200 mg tid group withdrew because of diarrhoea. CONCLUSION: Tolcapone prolongs "on" time in fluctuating parkinsonian patients while allowing a reduction in daily levodopa dosage, thereby improving the efficacy of long term levodopa therapy.

Aged↗