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M Jackson

Publications and source records attributed to M Jackson.

At least 127 records · Page 7Linked to original sources
PubMed1997

The effect of the proposed national data protection regime on the health sector in Australia.

The Commonwealth Government and a number of State governments are proposing to introduce legislation based on the Information Privacy Principles contained in the Privacy Act 1988 (Cwlth). This will allow individuals access to any personal information held on them by an organisation or person, including private practitioners, private health facilities and State government agencies. This article discusses this proposed legislation and its implications for the health sector. Although in the public health area patients can already gain access to their medical records through the use of the various Freedom of Information Acts and, in the case of Commonwealth government agencies, the Privacy Act 1988 (Cwlth), the proposed data protection legislation will provide more than access rights to individuals. The effect of the proposed legislation on the private sector, where no obligation exists on the part of the doctor to grant a patient access to his or her records, will be substantial.

Australia↗
PubMed1997

Mycobacterium tuberculosis Des protein: an immunodominant target for the humoral response of tuberculous patients.

The phoA gene fusion methodology permitted the identification of a new Mycobacterium tuberculosis exported protein, Des. This protein has significant sequence similarities to plant acyl-acyl carrier protein desaturases, which are enzymes involved in general fatty acid biosynthesis as well as in mycolic acid biosynthesis in mycobacteria. As shown by Western blot and enzyme-linked immunosorbent assay experiments, the Des protein is a major B-cell antigen that was recognized by all the tuberculous M. tuberculosis- and M. bovis-infected human patients tested.

Amino Acid Sequence↗
PubMed1997

Acyltransferase domain substitutions in erythromycin polyketide synthase yield novel erythromycin derivatives.

The methylmalonyl coenzyme A (methylmalonyl-CoA)-specific acyltransferase (AT) domains of modules 1 and 2 of the 6-deoxyerythronolide B synthase (DEBS1) of Saccharopolyspora erythraea ER720 were replaced with three heterologous AT domains that are believed, based on sequence comparisons, to be specific for malonyl-CoA. The three substituted AT domains were "Hyg" AT2 from module 2 of a type I polyketide synthase (PKS)-like gene cluster isolated from the rapamycin producer Streptomyces hygroscopicus ATCC 29253, "Ven" AT isolated from a PKS-like gene cluster of the pikromycin producer Streptomyces venezuelae ATCC 15439, and RAPS AT14 from module 14 of the rapamycin PKS gene cluster of S. hygroscopicus ATCC 29253. These changes led to the production of novel erythromycin derivatives by the engineered strains of S. erythraea ER720. Specifically, 12-desmethyl-12-deoxyerythromycin A, which lacks the methyl group at C-12 of the macrolactone ring, was produced by the strains in which the resident AT1 domain was replaced, and 10-desmethylerythromycin A and 10-desmethyl-12-deoxyerythromycin A, both of which lack the methyl group at C-10 of the macrolactone ring, were produced by the recombinant strains in which the resident AT2 domain was replaced. All of the novel erythromycin derivatives exhibited antibiotic activity against Staphylococcus aureus. The production of the erythromycin derivatives through AT replacements confirms the computer predicted substrate specificities of "Hyg" AT2 and "Ven" AT and the substrate specificity of RAPS AT14 deduced from the structure of rapamycin. Moreover, these experiments demonstrate that at least some AT domains of the complete 6-deoxyerythronolide B synthase of S. erythraea can be replaced by functionally related domains from different organisms to make novel, bioactive compounds.

Acyl Coenzyme A↗
PubMed1997

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<O.01 v 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. Diarrhea 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 diarrhea. 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↗
PubMed1997

Production of brominated tiacumicin derivatives.

Several novel tiacumicin derivatives containing bromine have been produced by the addition of inorganic bromine to the fermentation both of Dactylosporangium aurantiacum subsp, hamdenensis. Structures were elucidated employing mass spectrometry and NMR spectroscopy. Antibacterial activity of the bromotiacumicins is comparable to that of the parent compounds.

Actinomycetales↗
PubMed1997

Production of brominated tiacumicin derivatives

Several novel tiacumicin derivatives containing bromine have been produced by the addition of inorganic bromine to the fermentation broth of Dactylosporangium aurantiacum subsp. hamdenesis. Structures were elucidated employing mass spectrometry and NMR spectroscopy. Antibacterial activity of the bromotiacumicins is comparable to that of the parent compounds.

Journal Article↗
PubMed1996

B cells are exquisitely sensitive to central tolerance and receptor editing induced by ultralow affinity, membrane-bound antigen.

To assess the sensitivity of B cell tolerance with respect to receptor/autoantigen affinity, we identified low affinity ligands to the 3-83 (anti-major histocompatibility complex class I) antibody and tested the ability of these ligands to induce central and peripheral tolerance in 3-83 transgenic mice. Several class I protein alloforms, including Kbm3 and Dk, showed remarkably low, but detectable, affinity to 3-83. The 3-83 antibody bound Kb with K lambda approximately 2 x 10(5) M-1 and bound 10-fold more weakly to the Kbm3 (K lambda approximately 2 x 10(4) M-1) and Dk antigens. Breeding 3-83 immunoglobulin transgenic mice with mice expressing these ultralow affinity Kbm3 and Dk ligands resulted in virtually complete deletion of the autoreactive B cells from the peripheral lymphoid tissues. These low affinity antigens also induced receptor editing, as measured by elevated RAG mRNA levels in the bone marrow and excess levels of id- variant B cells bearing lambda light chains in the spleen. Reactive class I antigens were also able to mediate deletion of mature B cells when injected into the peritoneal cavity of 3-83 transgenic mice. Although the highest affinity ligand, Kk, was consistently able to induce elimination of the 3-83 peritoneal B cells, the lower affinity ligands were only partially effective. These results demonstrate the remarkable sensitivity of the deletion and receptor-editing mechanisms in immature B cells, and may suggest a higher affinity threshold for deletion of peripheral, mature B cells.

Animals↗
PubMed1996

Fibrous matrix of ventricular myocardium in tricuspid atresia compared with normal heart. A quantitative analysis.

BACKGROUND: The collagen matrix is a small component of the myocardium, but it provides a supportive framework. An increase in collagen in the pressure-overloaded ventricle is known to cause myocardial stiffness. However, little is known about the collagen matrix in the volume-overloaded ventricle, particularly in relation to congenital heart disease. METHODS AND RESULTS: We examined a total of 53 hearts with tricuspid atresia and 58 normal hearts matched for age. Using a microscopic-morphometric method, we analyzed the percentage per field area occupied by interstitial fibrous tissue in four sites in the ventricular mass for each specimen. A comparison of sampling sites showed no significant variations between normal and malformed hearts. Results from a homogeneity of regression co-efficients analysis suggested that the two groups shared the same basic relation of proportion of fibrosis with age. The use of ANCOVA, however, revealed a clear separation between the extents of fibrous tissue in the two groups of hearts. CONCLUSIONS: The myocardium of hearts with tricuspid atresia is consistently more fibrotic than normal heart and is probably an inherent part of the malformation. This difference could explain, at least in part, the clinical observation that the left ventricle is frequently abnormal, even at an early age.

Adolescent↗
PubMed1996

Enzyme-linked immunosorbent assays in a chromatographic format.

This paper describes the execution of enzyme-linked immunosorbent assays (ELISA), (i) in immunosorbent columns with antibodies immobilized on porous particles, (ii) where samples and reagents are metered by valves and syringe pumps, (iii) samples, reagents, substrate, and wash buffers are transported into or through the system by high pressure liquid chromatography pumps, and (iv) enzyme reaction product is detected by absorbance. The normal protocol used for ELISA was modified in that antigen was complexed with enzyme conjugated antibody in the autosampler and an aliquot introduced into the system where it was transported to the immunosorbent and captured. Substrate was subsequently pumped into the immunosorbent bed and the product swept to an absorbance detector for quantitation.

Animals↗
PubMed1996

Modification of the extracellular matrix following myocardial infarction monitored by FTIR spectroscopy.

Comparison of mid- and near-infrared spectra of control and infarcted rat ventricular tissue reveals the presence of absorptions in infarcted tissue which are highly characteristics of collagen, indicating large scale deposition of type I collagen in the myocardium following infarction. These results demonstrate that IR spectroscopy may be used to rapidly monitor the modifications of the extracellular matrix associated with myocardial infarction.

Animals↗
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↗