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Biomedical subjects

M Jackson

Publications and source records attributed to M Jackson.

At least 145 records · Page 8Linked to original sources
PubMed1996

Different patterns of cytokine induction in cultures of respiratory syncytial (RS) virus-specific human TH cell lines following stimulation with RS virus and RS virus proteins.

Human peripheral blood mononuclear cell (PBMC) proliferative responses to live respiratory syncytial (RS) virus, formalin-inactivated RS (Fl-RS) virus, RS virus F (fusion) protein, and RS virus G (attachment) protein were assessed. All donors responded to challenge with whole RS virus antigens and F and G proteins. F protein responses elicited higher levels of response than equivalent concentrations of G protein in nine out of ten adult RS-seropositive donors. Stimulation of PBMC induced low levels of interleukin 2 (IL-2), interferon gamma (IFN-gamma), IL-4, and IL-10 production. Human RS virus-specific T cell lines were generated from peripheral blood cultures following in vitro stimulation with RS virus antigens. All lines generated were shown to be MHC class II restricted. Characterisation of the lines was carried out by determining the levels of IL-2, IFN-gamma, IL-4, and IL-10 in culture supernatants. T cell lines enriched for RS virus-specific cells provided a more sensitive system than PBMC cultures for the detection of cytokines. The pattern of cytokine production varied for the individual lines, and the detection of TH1 and TH2 cytokines was dependent on the nature of the stimulating RS virus antigen. Live RS virus induced a TH1 pattern of cytokines (IL-2 and IFN-gamma), whereas FI-RS virus induced the production of both TH1 and TH2 cytokines. In addition, TH lines specific for individual RS virus proteins produced different cytokine profiles. F protein-specific lines generated TH1-type cytokines (IL-2 and IFN-gamma), whereas G protein-specific lines generated TH2-type cytokines (IL-4 and IL-10).

Adult↗
PubMed1996

Analysis of chromosome 5q13 genes in amyotrophic lateral sclerosis: homozygous NAIP deletion in a sporadic case.

Although defects in the gene encoding the enzyme cytosolic copper/zinc superoxide dismutase (SOD1) have been reported in 20% of familial amyotrophic lateral sclerosis (ALS) patients, the etiology of the remaining familial cases and the more common sporadic form of the disease remains unknown. Recently, deletions of the neuronal apoptosis inhibitory protein gene NAIP, of the survival motor neuron gene SMN, and of a further cDNA fragment, XS2G3, have been reported in childhood-onset proximal spinal muscular atrophy (SMA), another disorder with pathology restricted to the motor system. We have therefore investigated the possibility of alterations in SMN and NAIP in 154 patients with ALS (135 sporadic cases, 17 familial cases). None of these patients revealed mutations in SMN by single-strand conformation polymorphism analysis. A single patient revealed a partial deletion of NAIP, with a homozygous absence of NAIP exon 5. While it is possible that this individual is one of the rare carriers of SMA who show NAIP deletions, a further explanation is that the NAIP deletion is in some way contributing to the ALS phenotype in this individual.

Amyotrophic Lateral Sclerosis↗
PubMed1996

Motor neurone disease-inclusion dementia.

We describe nine patients, five women and four men (age at death 58-83 years), who developed isolated progressive frontotemporal dementia over 4 to 12 years. These cases represent nine of the 385 (2.3%) cases from a series of autopsy cases of dementia in a large teaching hospital. One had a mother with a history of frontotemporal dementia and marked frontal lobe atrophy. Another had multiple affected family members with frontotemporal dementia, motor neurone disease or both. None of the nine had clinical evidence of either an upper or lower motor neurone disorder. In each case neuropathological examination revealed cortical pathology identical to that described previously as typical of dementia associated with motor neurone disease. There was variable macroscopic atrophy and neuronal loss in the frontal and temporal lobes. All cases had cortical microvacuolation, in seven limited to cortical layer II, and transcortical in two. There was variable cortical and subcortical gliosis. Intraneuronal ubiquitin-immunoreactive inclusions, characteristic of the extra-motor involvement of motor neurone disease, were found in the hippocampal dentate granule cells and residual neurones in layer II of the frontotemporal cortex of all cases. Similar inclusions were also seen in the nucleus ambiguus of three cases. The hypoglossal nuclei showed no neuronal loss, gliosis or ubiquitin-immunoreactive inclusions. Ubiquitin-immunoreactive dystrophic neurites were detected within affected cortex, being most conspicuous in layer II in areas containing microvacuolation. Dystrophic neurites were not detected in subcortical structures. Spinal cords were unavailable for examination because of limited autopsy consent. The finding of intraneuronal ubiquitin-immunoreactive inclusions characteristic of motor neurone disease in patients with frontotemporal dementia, without clinical or pathological evidence of motor system degeneration, extends the clinical spectrum of diseases associated with such inclusions. We propose the term motor neurone disease-inclusion dementia (MNDID) for these cases.

Aged↗
PubMed1996

The new neuropathology of degenerative frontotemporal dementias.

The clinical features and recent developments in the neuropathology of frontotemporal dementia are reviewed. The five main neurodegenerative disorders that underlie the clinical syndrome of frontotemporal dementia are distinguished using immunohistochemistry with antisera to ubiquitin and tau proteins. Motor neuron disease-type dementia is characterised by ubiquitin-immunoreactive intraneuronal inclusions in cortical layer II and the hippocampal dentate granule cells. A diagnosis of Alzheimer's disease changes is based upon the presence of neurofibrillary tangles, which immunostain with antibodies to tau and ubiquitin, and many associated neuritic plaques. Corticobasal degeneration is diagnosed by the presence of tau-immunoreactive, but ubiquitin-non-reactive intraneuronal inclusions in cortical layer II and the substantia nigra. Pick's disease is restricted to cases with tau- and ubiquitin-immunoreactive spherical cortical intraneuronal inclusions (Pick bodies), best seen in the hippocampal dentate gyrus and frontotemporal cortex. Dementia of frontal type is the preferred term for cases in which no intraneuronal inclusions are seen with antisera to tau and ubiquitin. A practical approach to the pathological diagnosis of frontotemporal dementia and the differential diagnosis of the five disorders using immunohistochemical studies is provided.

Alzheimer Disease↗
PubMed1996

Cytokine mRNA expression in cutaneous warts: induction of interleukin-1 alpha.

The persistence of human papillomavirus at cutaneous sites may be due to impaired trafficking of immune effector cells to the epidermis. We investigated whether HPV infection modulates cytokine mRNA expression in skin, thereby influencing local immunity. The mRNA expression of tumour necrosis factor-alpha, interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-1 receptor antagonist (IL-1ra), IL-4, IL-8, IL-10, IL-12, granulocyte macrophage colony-stimulating factor, transforming growth factor-beta, interferon-gamma and amphiregulin were assayed in cutaneous warts and normal skin by semiquantitative reverse transcriptase-polymerase chain reaction. The expression of the cytokines was heterogeneous in the specimens but, of the 12 mRNA species investigated, only IL-10 mRNA was significantly downregulated in warts compared with normal skin (P = 0.002). IL-1 alpha mRNA expression was significantly upregulated in common warts (P = 0.019) and plantar warts (P = 0.003) compared with normal skin. The expression of IL-1 alpha and IL-1ra mRNAs were significantly correlated in plantar warts (P < 0.05). Warts expressing IL-1 alpha also expressed amphiregulin, and there was a significant correlation between the expression of these two genes (P < 0.05). It is possible that IL-1 alpha expression in cutaneous warts may modulate the growth of papillomavirus-infected keratinocytes, mediated by amphiregulin, thus ensuring viral persistence.

Adolescent↗
PubMed1996

Early experiences with the AO calcaneal fracture plate.

We describe our early experiences using the new AO plate for open reduction and internal fixation of displaced intra-articular fractures of the calcaneum. An overview of our operative technique based on 22 cases is given. The relative merits of the new plate are discussed and we conclude that the plate is a useful device for dealing with this complex injury.

Adult↗
PubMed1996

Stage specific expression of proliferating cell nuclear antigen and DNA polymerase delta from Plasmodium falciparum.

Antisera raised against proliferating cell nuclear antigen (PfPCNA) and DNA polymerase delta (PfDNA Pol delta) have been used against extracts from synchronised parasites to show that both proteins accumulate in trophozoites and persist in schizonts. The steady-state transcripts from both PfPCNA and PfDNA Pol delta also accumulate at the trophozoite stage. However, nuclear run on analysis shows that, whereas PfDNA Pol delta promoter activity is absent in rings but present in trophozoites and schizonts, the PfPCNA promoter is active throughout the intraerythrocytic cycle. This suggests that mechanisms regulating the expression of these two genes may be different although their coordinated activity is required for DNA replication.

Animals↗
PubMed1996

Anatomic patterns of carotid endarterectomy healing.

BACKGROUND: Restenosis after carotid endarterectomy is a dynamic process likely influenced by surgical technique as well as by anatomic, hemodynamic, and patient factors. METHODS: To characterize the healing of carotid endarterectomy sites, intraoperative and serial postoperative color duplex scans were performed in 126 patients (136 repairs). Vessel-wall imaging, midstream spectral analysis, and measurements of diameter and cross-sectional area from common carotid artery (CCA) and internal carotid artery (ICA) segments were compared (at 3, 6, 15, and 30 months) and severity of lumen stenosis was determined. RESULTS: After primary closure (n = 15), patch angioplasty (n = 121), or intraoperative revision based on duplex scanning (n = 5), 12 repairs had mild residual flow abnormalities and 1 repair had a moderate flow abnormality. Mean ICA bulb diameter was greater in patched repairs (0.81 cm, range 0.6 to 1.1 cm) than primary closed repairs (0.7 cm, range 0.45 to 0.8 cm). No ICA occluded during follow-up (mean 24 months), and three repairs, two in the ICA and one in the CCA, demonstrated 50% to 75% diameter reduction at 9 months. Lumen cross-sectional area of vein-patched repairs increased 0.6 cm2 to 0.76 cm2 (P < 0.01) in the ICA and 0.69 cm2 to 1.1 cm2 (P < 0.01) in the CCA segments by 3 months compared with intraoperative measurement. Four patients with progressive dilatation of the patch segment to a mean of 1.77 cm2 developed asymptomatic posterior wall mural thrombus. Postoperative blood flow velocities measured through the repair were similar to intraoperative values. Minor intraoperative hemodynamic abnormalities were not associated with the development of restenosis, and changes in repair site anatomy occurred within 3 months with little change thereafter. CONCLUSIONS: We have found intraoperative scanning useful for detection of anatomic defects and associated turbulence, lesions that should be immediately corrected. Surgical technique that achieves normal intraoperative carotid flow hemodynamics and B-mode ultrasonic vessel wall appearance should predict an endarterectomized segment free of significant residual plaques and neointimal hyperplasia. Tailoring of the vein patches to achieve lumen diameters < 1 cm is recommended because of the dilataton likely to develop after surgery that may lead to vessel wall mural thrombus.

Analysis of Variance↗
PubMed1996

In situ characterization of beta-amyloid in Alzheimer's diseased tissue by synchrotron Fourier transform infrared microspectroscopy.

We report the first evidence of the structure of beta-amyloid protein as it exists in situ within a slice of human Alzheimer's diseased brain tissue. Using a Fourier transform infrared microspectroscopic technique, areas of interest can be selected for spectral measurements with regions of potential contamination masked. In so doing, it is possible to obtain infrared spectra only of beta-amyloid and not the surrounding grey matter within which it lies. However, to obtain spectra of high-quality signal-to-noise ratio using a conventional infrared source, we were limited to aperture sizes between 24 microns x 24 microns to 50 microns x 50 microns. Markedly improved high-quality spectra were acquired with infrared radiation provided by a synchrotron light source (National Synchrotron Light Source, Brookhaven National Laboratories), using aperture sizes as small as 12 microns x 12 microns. This allowed spectroscopic mapping of brain tissue regions containing amyloid. We observe that in situ protein of grey matter exist predominantly in an alpha-helical and/or unordered conformation, whereas within amyloid deposits a beta-sheet structure predominates. The hydrogen bonding strength of the beta-structure found in situ is different from that reported in the literature for isolated/chemically synthesized beta-amyloid peptides.

Alzheimer Disease↗
PubMed1996

Analysis of a cation-transporting ATPase of Plasmodium falciparum.

We have cloned and characterised one gene, PfATPase4 which encodes a P-type ATPase containing all the primary sequence motifs characteristic of this class of transmembrane ion transporters, and also a fragment of a second P. falciparum P-type ATPase pseudogene (PfATPase5). Analysis of conserved domains and motifs of specific ATPases reveals that PfATPase4 is most analogous to Ca2+ ATPases of the endoplasmic reticulum. The PfATPase4 gene gives rise to a transcript of 8 kb shortly after erythrocyte invasion. Although this mRNA is not detected in later stages, the protein detected immunologically at 190 kDa persists throughout and is detected in free merozoites. Immunofluorescence microscopy reveals that the PfATPase4 protein is concentrated in discrete compartments at the periphery of the parasite. Detailed sequence and structural analyses of these and the other P-type ATPases of P. falciparum described previously, reveals that they comprise an unusual family in several respects. Firstly, the large number of non-homologous genes so far characterised reflects the complexities of ionic regulation in the diverse environments encountered by the parasite. Secondly, the plasmodial P-type ATPase family may be classified both at primary sequence and structural levels into two distinct groups-those typical of P-type ATPases (including PfATPase4) and those which are much more divergent. A third complexity is illustrated by the fact that one of the other members [1] here termed PfATPase6, has an even greater similarity to the sarcoplasmic reticulum Ca2+ ATPases than does PfATPase4, which raises questions about the possible functional relationship between these two members.

Adenosine Triphosphatases↗
PubMed1996

Issues affecting refurbishment and re-use of pacemakers.

This paper discusses the problems associated with the refurbishing and re-use of medical devices which are sold by manufacturers as 'single use items' by focusing in particular on the re-use of pacemakers. Re-use of single-use devices such as pacemakers does occur in Australia, and in many other parts of the world, but there has been little public awareness of this fact. The paper explains and discloses medical, legal and ethical issues which arise through the re-use of pacemakers. It also discusses the recommendations of the 1995 'Draft report of the NHMRC Expert Panel on Re-Use of Medical Devices Labelled as Single Use'.

Australia↗
PubMed1996

Gastroesophageal reflux and tracheobronchial contamination after cardiac surgery: should a nasogastric tube be routine?

Nasogastric (NG) tubes are routinely used in patients undergoing cardiac surgery. This randomized study was designed to assess gastroesophageal reflux (GER) without a NG tube (control) compared with a NG tube managed either by gravity drainage (gravity) or continuous low-grade suction (suction). Antimony pH probes were placed in the lower esophagus and trachea after induction of anesthesia in 51 patients, and pH was recorded every 5 s until the time of tracheal extubation. GER was defined as reversible decrease in esophageal pH to less than 4.0. No significant difference was found between groups in age, weight, gender, duration of postoperative ventilation, morphine use, or antiemetic use. All indicators of GER were seen more frequently in the gravity group compared with the two other groups (P < 0.001). One episode of sudden decrease in tracheal pH was observed in a patient in the gravity group, indicating tracheal aspiration, which was associated with delayed extubation and postoperative pneumonia. The absence of a NG tube is not associated with reflux, probably since the gastroesophageal sphincter remains competent. NG tubes are not routinely necessary for cardiac surgery in patients without risk factors for GER, and increase reflux risk if managed without low-grade suction.

Aged↗
PubMed1996

Acute pain after thoracic surgery predicts long-term post-thoracotomy pain.

OBJECTIVE: Long-term pain is a common sequela of thoracotomy, occurring in approximately 50% of patients 2 years after thoracic surgery. Despite this alarming statistic, little is known about the factors responsible for the transition of acute to chronic pain. The aim of the present study is to identify predictors of long-term post-thoracotomy pain. DESIGN: Follow-up was for 1.5 years for patients who had participated in a prospective, randomized, controlled trial of preemptive, multimodal analgesia. SETTING: Subjects were recruited from a tertiary care center. PATIENTS: Thirty patients who had undergone lateral thoracotomy were followed up by telephone, administered a structured interview, and classified according to long-term pain status. MAIN OUTCOME MEASURES: Present pain status was measured by a verbal rating scale (VAS). Measures obtained within the first 48 h after surgery were compared between patients with and without pain 1.5 years later. These include VAS pain scores at rest and after movement, McGill Pain Questionnaire data, patient-controlled morphine consumption (mg), and pain thresholds to pressure applied to a rib contralateral to the thoracotomy incision. RESULTS: Fifty-two percent of patients reported long-term pain. Early postoperative pain was the only factor that significantly predicted long-term pain. Pain intensity 24 h after surgery, at rest, and after movement was significantly greater among patients who developed long-term pain compared with pain-free patients. A significant predictive relationship was also found at 24 and 48 h using the McGill Pain Questionnaire. Cumulative morphine was comparable for the two groups. Pain thresholds to pressure applied to a rib contralateral to the incision did not differ significantly between the groups. CONCLUSION: Aggressive management of early postoperative pain may reduce the likelihood of long-term post-thoracotomy pain.

Acute Disease↗
PubMed1996

The Mycobacterium tuberculosis purine biosynthetic pathway: isolation and characterization of the purC and purL genes.

Genes from the Mycobacterium tuberculosis purine biosynthetic pathway were identified using purine auxotrophic mutants of Mycobacterium smegmatis obtained by Tn611 transposon mutagenesis. Two approaches were followed in parallel. The first consisted of the complementation of the M. smegmatis purine auxotrophs using a M. tuberculosis H37Rv shuttle cosmid library. In the second approach, specific probes corresponding to the regions adjacent to the insertion sites of Tn611 in the M. smegmatis genome were used to screen a M. tuberculosis plasmid library by colony hybridization for inserts carrying homologous DNA fragments. Nucleotide sequence analysis of two M. tuberculosis genes isolated by these methods revealed high similarities with purC and purL genes from other bacterial and fungal sources. Transcriptional start sites were mapped for both genes, which revealed similar-10 boxes but with a higher GC content than the Escherichia coli sigma 70 consensus.

Amino Acid Sequence↗
PubMed1996

Prognosis of supravalve aortic stenosis in 81 patients in Liverpool (1960-1993).

OBJECTIVE: To determine the prognosis of supravalve aortic stenosis into early adult life and the factors affecting this prognosis. DESIGN: 81 patients with supravalve aortic stenosis were followed for a median duration of 8.3 (range 1 to 29) years. PATIENTS: 40 patients (49.4%) had Williams' syndrome, 18 (22.2%) familial supravalve aortic stenosis, 18 (22.2%) sporadic supravalve aortic stenosis, and five (6.2%) other syndromes. Nineteen patients had additional levels of left ventricular outflow tract obstruction. RESULTS: 47 patients (58%) underwent operation; 20% within a year of presentation. Multivariable analysis predicted that 88% of patients would undergo intervention within 30 years of follow up. The chance of intervention was increased by more severe aortic stenosis at presentation and the presence of multilevel obstruction in patients with sporadic supravalve aortic stenosis. Three deaths occurred before operation and 13 within a month of operation. Ten (62.5%) of the postoperative deaths were in patients with multilevel obstruction. Predicted survival 30 years after presentation was 66%. Risk factors for survival were age and severity of aortic stenosis at presentation. Multilevel obstruction did not emerge as a significant risk factor for death because of the high association with the severity of stenosis at presentation. 74% of survivors had mild or insignificant stenosis at follow up. CONCLUSIONS: Long-term survival is related to age and the severity of aortic stenosis at presentation. Most patients will require intervention, and most survivors will have mild stenosis.

Aortic Valve Stenosis↗