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Biomedical subjects

D A Mackenzie

Publications and source records attributed to D A Mackenzie.

18 recordsLinked to original sources
PubMed2005

Chemometric treatment of vanillin fingerprint chromatograms. Effect of different signal alignments on principal component analysis plots.

This study describes the chemometric treatment of vanillin fingerprint chromatograms to distinguish vanillin from different sources. Prior to principal component analysis, which is used to discriminate vanillin from different origins, the fingerprints are aligned. Three alignment algorithms are tested, correlation optimized warping (COW), target peak alignment (TPA) and semi-parametric time warping (STW). The performance of the three algorithms is evaluated and the effect of the different alignments on the PCA score plots is investigated. The alignment obtained with STW differs somewhat from that with COW and TPA. However, equivalent score plots were obtained regarding the different vanillin groups.

Algorithms↗
PubMed2000

Quantitative assessment of IgG antibodies to Helicobacter pylori and outcome of ischaemic heart disease.

Criticisms of serological studies on Helicobacter pylori and ischaemic heart disease (IHD) include: undiagnosed heart disease in live controls; no assessment of severity or outcome of IHD; and qualitative not quantitative measurements of IgG to the bacteria. The aim was to assess quantitatively IgG levels specific for H. pylori (ng ml(-1)) among patients who survived a myocardial infarction (MI) with those who died of IHD. Sera were from four groups: (1) men who survived one MI; (2) men matched for age and socioeconomic background to group 1; (3) individuals who died suddenly of IHD; (4) accidental deaths matched for age and sex to group 3. Levels of IgG to H. pylori increased with age (P<0.005) but were not associated with smoking or socioeconomic groups. There was a correlation between IgG to the bacteria and decreasing socioeconomic levels only among group 1 (P<0.01). IgG levels were higher for subjects who died of heart disease (median=151 ng ml(-1)) compared with survivors (median=88 ng ml(-1)) (P=0.034) and higher for survivors compared with their controls (median=58 ng ml(-1)) (P=0.039). Future serological studies of H. pylori in relation to IHD should be quantitative and severity of disease considered in analyses.

Antibodies, Bacterial↗
PubMed2000

Isolation and use of a homologous histone H4 promoter and a ribosomal DNA region in a transformation vector for the oil-producing fungus Mortierella alpina.

Mortierella alpina was transformed successfully to hygromycin B resistance by using a homologous histone H4 promoter to drive gene expression and a homologous ribosomal DNA region to promote chromosomal integration. This is the first description of transformation in this commercially important oleaginous organism. Two pairs of histone H3 and H4 genes were isolated from this fungus. Each pair consisted of one histone H3 gene and one histone H4 gene, transcribed divergently from an intergenic promoter region. The pairs of encoded histone H3 or H4 proteins were identical in amino acid sequence. At the DNA level, each histone H3 or H4 open reading frame showed 97 to 99% identity to its counterpart but the noncoding regions had little sequence identity. Unlike the histone genes from other filamentous fungi, all four M. alpina genes lacked introns. During normal vegetative growth, transcripts from the two histone H4 genes were produced at approximately the same level, indicating that either histone H4 promoter could be used in transformation vectors. The generation of stable, hygromycin B-resistant transformants required the incorporation of a homologous ribosomal DNA region into the transformation vector to promote chromosomal integration.

DNA, Fungal↗
PubMed1997

Ankylosing spondylitis and secretor status: a re-evaluation.

Non-secretion of ABO blood group substances in body fluids is associated with susceptibility to some bacterial infections. Non-secretors were previously found to be over-represented in patients with ankylosing spondylitis (AS) (49%) compared to controls (27%). Re-evaluation of secretor status in a population of 92 AS patients and 103 controls revealed identical proportions of non-secretors (28%). Of 43 patients studied in both surveys, 6/22 typed initially as non-secretors proved to be secretors using both haemagglutination inhibition assay (HAI) and enzyme-linked immunosorbent assay (ELISA) techniques. Loss of secreted blood group antigens in the saliva is the cause of this mis-typing. Careful attention to the method of collection, handling and preservation of saliva specimens is essential for accurate assessment of secretor status. Therefore, there is no link between secretor status and AS.

ABO Blood-Group System↗
PubMed1996

Gamma delta T lymphocyte responses to HIV.

Natural immunity may be involved in controlling viral spread in hosts infected with HIV. A panel of gamma delta T cell receptor-positive lymphocyte clones was isolated from the peripheral blood of healthy HIV- donors and tested for anti-HIV cytotoxic responses. Twelve of 30 (40%) V gamma 9+/V delta 2+ T cell clones, but none of seven V delta 1+ T cell clones, displayed lytic activity against HIV-infected cells. The V gamma 9+/V delta 2+ clones cytotoxic for HIV-infected cells also lysed Daudi cells. However, not all V gamma 9+/V delta 2+ clones which lysed Daudi targets had the capacity to lyse HIV-infected cells. Some of the gamma delta T cell clones were also investigated for potential proliferative responses to HIV-infected cells. One V gamma 9+/V delta 2+ T cell clone (ME8-7) and one V delta 1+ T cell clone (ME18-2) demonstrated proliferative responses towards HIV-infected cells. Another V gamma 9+/V delta 2+ clone (VM39) proliferated in response to cell-free HIV. Taken together, these results provide direct evidence of anti-HIV gamma delta T cell responses in healthy, HIV- persons.

Clone Cells↗
PubMed1994

Strategies for improving heterologous protein production from filamentous fungi.

Despite the naturally high capacity for protein secretion by many species of filamentous fungi, secreted yields of many heterologous proteins have been comparatively low. The strategies for yield improvement have included the use of strong homologous promoters, increased gene copy number, gene fusions with a gene encoding a naturally well-secreted protein, protease-deficient host strains and screening for high yields following random mutagenesis. Such approaches have been effective with some target heterologous proteins but not others. Approaches used in heterologous protein production from filamentous fungi are discussed and a perspective on emerging strategies is presented.

Animals↗
PubMed1994

Transcriptional and post-transcriptional events affect the production of secreted hen egg white lysozyme by Aspergillus niger.

The relationship between heterologous gene copy number, mRNA and secreted protein yields has been studied in Aspergillus niger transformants containing either the hen egg-white lysozyme (HEWL) cDNA gene or a glucoamylase-HEWL gene fusion (incorporating the A. niger glaA gene). The results support a direct relationship between HEWL gene copy number, mRNA and secreted HEWL protein levels at low (< 25) copy numbers. High protein yields are associated with multiple copies of the recombinant gene at a single site. Fusion of the HEWL gene to the glucoamylase gene resulted in higher steady-state levels of heterologous mRNA. Transformants with the HEWL cDNA alone exhibited a ten-fold higher mRNA:protein ratio than transformants with the gene fusion indicating that post-transcriptional events significantly affect final secreted protein yields.

Animals↗
PubMed1994

The role of infectious agents in sudden infant death syndrome.

Epidemiological factors associated with susceptibility to respiratory infections are similar to those associated with Sudden Infant Death Syndrome. Here we review the evidence that respiratory pathogens might be involved in some cases of Sudden Infant Death Syndrome in the context of factors identified in epidemiological studies of cot deaths: the age range affected; mother' smoking; respiratory viral infections; immunisation status. Both laboratory and epidemiological evidence suggests that vulnerability of infants to infectious agents depends on interactions between genetic, developmental and environmental factors that contribute to colonisation by microorganisms, the inflammatory and specific immune responses and the infants' physiological responses to inflammatory mediators. A model is proposed to explain how microorganisms might trigger a series of events resulting in some of these unexpected deaths and discusses how the the present recommendations regarding child care practices might help reduce the numbers of Sudden Infant Death Syndrome cases associated with infectious agents.

Bacterial Infections↗
PubMed1993

PC/VAX or standalone PC-based general purpose biological data collection system.

A system, to collect, analyse and display biological data, is developed using IBM PC AT compatibles (PCs) or CED1401/1609 devices networked to a VAX environment. It can be operated in three separate modes: using the CED/IEEE/VAX network; using the PC/Ethernet/VAX network; as a standalone PC. The original system comprised CED 1401/1609 data collection devices running on the IEEE bus. This has been superseded by a PC-286 or better incorporating an analogue-to-digital convertor (DT2824-PGH) and a communications interface board (DEPCA) linked by thinwire Ethernet (ThinWire) running DECnet with their product network application software PCSA. This network has not only doubled the original throughput but has also removed the two major IEEE constraints: 4 m between devices and the physical linking of devices to the VAX. The PCs are logically linked to clustered VAXes on Ethernet, giving flexible networking supporting multiple ThinWire segments, each supporting a maximum of 30 PCs per 185 m segment length. As the enhanced design compliments the original, both may operate concurrently, appear similar in operation to the user and use the same analysis software, all of which help reduce the rate of system obsolescence.

Computer Communication Networks↗
PubMed1992

Factors influencing oral carriage of yeasts among individuals with diabetes mellitus.

A total of 439 individuals with diabetes mellitus were examined for carriage of yeasts by the oral rinse and palatal swab techniques. Eighteen genetic or environment variables were assessed for their contribution to carriage of yeasts. The factor contributing to palatal and oral carriage of yeasts among individuals with insulin dependent diabetes mellitus (IDDM) was age (P < 0.01). The factor contributing to palatal carriage of yeasts among individuals with non-insulin dependent diabetes mellitus (NIDDM) was poor glycaemic control (glycosuria P < 0.01); carriage in the oral cavity as a whole was influenced additionally by non-secretion of ABH blood group antigens (P < 0.05). Introduction of a denture altered the above risk factors. For individuals with IDDM, oral carriage was associated with the presence of retinopathy (P < 0.05); palatal carriage was influenced by poor glycaemic control (HbA1P < 0.01, plasma glucose levels P < 0.05) and age (P < 0.05). For those with NIDDM, palatal carriage was associated with continuous presence of the denture in the mouth (P < 0.01); oral carriage was associated with plasma glucose levels (P < 0.05).

Adult↗
PubMed1991

Heterologous protein production by filamentous fungi.

There are clearly many facets to successful production of heterologous proteins from filamentous fungi. The objectives are to exploit the natural ability of some species to secrete high levels of protein. The heterologous target proteins produced in a fungal host must be acceptable to the public and be economic to produce, i.e. the targets must be authentic (in structure and activity) and be produced in high yield to necessary levels of purity. The appearance of heterologous products from fungi on the market is testament to some success but, equally, there are considerable limitations in our ability to produce desired yields of many target proteins. We endorse the view of van den Hondel, Punt and van Gorcom (1991) that for the commercial production of heterologous proteins from filamentous fungi more information is required on transcriptional control, introns, mRNA stability and processing, translational efficiency, protein secretion, glycosylation and proteolysis. In addition, there is scope for yield improvement based on a better understanding of the physiology of growth/product secretion coupled to appropriate bioreactor operation. The authenticity of product is an aspect which will assume increasing importance, particularly for therapeutic proteins. The level at which the structures and functional activity of heterologous proteins are assessed will ultimately be determined by legislation. The analytical methods currently available are not always sufficient, for example, to reveal folded structures, and most proteins are not amenable to analysis by two-dimensional NMR. The authenticity of target heterologous proteins will also need to be assessed in relation to the glycosylation level and pattern. This is not easily done and explains the paucity of detailed information published to date on glycosylation of fungal proteins. Novel engineered proteins are already being produced from filamentous fungi where expression is an aid to investigation of structure-function relationships. Commercial production of such engineered proteins will require approval subject to a range of stringently applied tests and analyses. This imposes an even greater need to be able to specify and control, in a rational manner, the structures of recombinant proteins. The research needs for realization of improved yields are equally important in assuring authenticity of product. It is encouraging that progress is being made on all fronts, primarily with Aspergillus spp. and T. reesei, but also with other species, such as N. crassa.

Animals↗
PubMed1989

Distributed computer system for capture, analysis and display of biological data.

A distributed real-time computer system has been developed to automate the collection, analysis and display of biological (pharmacological) data. It comprises a series of laboratory interface devices (CED 1401/1609) connected to a micro-VAX II via multiple IEEE-488 buses. The micro-VAX II is integrated to the main site computers using Ethernet running DECnet. The micro-VAX II system supports a multi-user, multipreparation and multitasking environment and it provides rapid transfer, storage, analysis and display of data. The system saves the pharmacologists from the manual analysis of their data, typically saving them four days of analysis per experiment and has improved both the quality of data detected and their subsequent analysis. Also, the development of a standard data capture procedure on common hardware along with the modular design of application software has almost quartered project development times.

Computer Communication Networks↗
PubMed1987

Magnetic resonance imaging to diagnose intralobar pulmonary sequestration.

Confirmation of the diagnosis of intralobar pulmonary sequestration has usually required angiographic demonstration of the systemic arterial supply. We report a young man who presented with non-resolving pneumonia where magnetic resonance imaging (MRI) suggested the correct diagnosis by demonstrating two arteries arising from the aorta supplying the sequestrum. MRI appears to offer a safe, noninvasive alternative for the diagnosis of sequestration.

Adult↗
PubMed1978

Missed, maluniting, and malunited fractures of the lateral humeral condyle in children.

Five cases of fracture of the lateral humeral condyle in children are described to illustrate the importance of recognition and proper management of this injury. The cases represent different degrees of severity of this injury. Failure of recognition of this fracture leads to serious late complications. Management of missed and maluniting fractures is discussed. It is our practice to internally fix these injuries.

Casts, Surgical↗
PubMed1978

Scoliosis in arthrogryposis multiplex congenita.

Fourteen of 50 patients studied with arthrogryposis also had scoliosis, an incidence of 28%. Eight patients developed a severe curve associated with functional disability and poor health. Three patients were unable to walk independently, and 2 died in childhood. Seven patients had congenital scoliosis; 4 had long "C" neuromuscular curves, and 3 had scoliosis associated with pelvic obliquity caused by unilateral hip dislocation or contracture. The natural history of congenital and neuromuscular curves was progression to an extreme and rigid scoliosis. The authors urge others to look for scoliosis in their patients with arthrogryposis and to anticipate its progression.

Arthrogryposis↗