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Biomedical subjects

K Mackenzie

Publications and source records attributed to K Mackenzie.

At least 19 recordsLinked to original sources
PubMed2005

Comparative analysis of population genetic structure in Athyrium distentifolium (Pteridophyta) using AFLPs and SSRs from anonymous and transcribed gene regions.

To examine the performance and information content of different marker systems, comparative assessment of population genetic diversity was undertaken in nine populations of Athyrium distentifolium using nine genomic and 10 expressed sequence tag (EST) microsatellite (SSR) loci, and 265 amplified fragment length polymorphism (AFLP) loci from two primer combinations. In range-wide comparisons (European vs. North American populations), the EST-SSR loci showed more reliable amplification and produced more easily scorable bands than genomic simple sequence repeats (SSRs). Genomic SSRs showed significantly higher levels of allelic diversity than EST-SSRs, but there was a significant correlation in the rank order of population diversities revealed by both marker types. When AFLPs, genomic SSRs, and EST-SSRs are considered, comparisons of different population diversity metrics/markers revealed a mixture of significant and nonsignificant rank-order correlations. However, no hard incongruence was detected (in no pairwise comparison of populations did different marker systems or metrics detect opposingly significant different amounts of variation). Comparable population pairwise estimates of F(ST) were obtained for all marker types, but whilst absolute values for genomic and EST-SSRs were very similar (F(ST) = 0.355 and 0.342, respectively), differentiation was consistently higher for AFLPs in pairwise and global comparisons (global AFLP F(ST) = 0.496). The two AFLP primer combinations outperformed 18 SSR loci in assignment tests and discriminatory power in phenetic cluster analyses. The results from marker comparisons on A. distentifolium are discussed in the context of the few other studies on natural plant populations comparing microsatellite and AFLP variability.

Cluster Analysis↗
PubMed2003

The dysphonic voice heard by me, you and it: differential associations with personality and psychological distress.

Voice production is subject to and indicative of psychological status. The precise relationships of voice disorders and psychological variables remain unclear. We compared the correlations of self-reported and more objective measures of voice quality in dysphonic patients with personality, coping, affect and somatization. Two hundred and four subjects participating in a randomized, controlled trial of speech therapy underwent self-report, observer rating and computer acoustic analysis of voice quality. These three indices of voice quality were compared with regard to their correlations with individual differences in neuroticism, alexithymia, negative emotion coping, anxiety, depression, neurotic symptoms, medically unexplained symptoms and quality of life. Significant correlations were observed between self-reported voice problems and all of the personality/coping and clinical psychological distress measures. People who reported more voice problems had: higher neuroticism and alexithymia; a tendency to use emotion-oriented coping; more psychological distress; poorer quality of life; and more past medically unexplained symptoms. Expert voice rating correlated weakly with neurotic disturbance, quality of life and previous medically unexplained symptoms. Objective voice assessment (amplitude perturbation) showed no significant associations with any psychological measure. The strongest associations of psychological variables and voice measures are with self-report measures. This suggests that it is in part the patients' perception of their own voice quality which accounts for the association of voice production and psychological factors in subjects presenting to voice clinics.

Adolescent↗
PubMed2003

Is there a progression of histologic grade from radical prostatectomy to local recurrence in patients with clinically isolated local recurrence following surgery?

OBJECTIVE: To evaluate whether there is any histologic progression from radical prostatectomy (RP) to local recurrence in patients with clinically isolated local recurrence following RP. METHODS AND MATERIALS: A total of 43 patients with clinically isolated, biopsy proven, local recurrence following RP were retrospectively analyzed with respect to the change in Gleason score (GS) from RP to local recurrence. Central pathology review was undertaken for both RP and local recurrence biopsy specimens. The changes in primary and secondary Gleason grade (GG), and any potential correlation between the extent of GS change and other variables were also examined. RESULTS: Median age at the time of local recurrence was 67 years (range: 55-78). Median interval between RP and local recurrence was 3.6 years (range: 0.3-17.7). Eight had a short course (<3 months) of hormone therapy prior to RP. Initial GS of RP specimens was 5, 6, 7, 8, and 9 in 1, 3, 29, 1, and 9 patients, respectively. At the time of local recurrence, GS was upgraded in 13, unchanged in 23, and downgraded in 7. The extent of GS change was correlated with the interval between RP and local recurrence, but not with pathological T stage or age. CONCLUSION: There was no statistically significant change in GS from RP to local recurrence, although there was a trend toward a higher GS at the time of local recurrence. The extent of GS change was associated positively with the elapsed time to local recurrence.

Adenocarcinoma↗
PubMed2002

The quality of life impact of dysphonia.

Dysphonia can affect social life and employment, but formal studies of its general health impact are lacking. The aims of this study were (i) to compare self-rated general health status as measured by the SF-36 in a large cohort of dysphonic patients with those from normative groups; and (ii) to examine the differential impact of dysphonia on the various health status domains. The 163 dysphonic voice clinic attendees (38 men, 125 women) were drawn from recruits to a prospective trial of speech therapy efficacy. The Short-Form 36 (SF-36) scores were compared with published data on 744 age-matched healthy controls. Patients with dysphonia had significantly poorer self-reported health than the controls on all eight SF-36 subscales (limitation of physical activity P < 0.05; other seven, all P < 0.001, Student's t-test). We thus conclude that dysphonia in patients without obvious laryngeal disease has an adverse impact on all health status subscales as measured by the SF-36. The study provides further evidence for the inclusion quality of life measures in otolaryngology baseline and outcome assessments.

Adolescent↗
PubMed2001

Sorption of pyrene to dissolved humic substances and related model polymers. 1. Structure--property correlation.

Solid-phase microextraction (SPME) was employed to determine sorption coefficients for pyrene on dissolved humic substances (DHS) of various origins and also on model polymers to gain a better understanding of the relationships between sorption potential and sorbent structures. The sorption potential of DHS from very different sources is described by an empirical two-parameter correlation involving the polarity (O/H atomic ratio) and the aromaticity (epsilon 280 nm) as descriptors. On the other hand, sorption experiments with well-defined model polymers, poly(acrylic acid) esters, led to the conclusion that aliphatic chains may be more effective than aromatic moieties in binding PAHs. The molecular weight of the model sorbents was found to have a significant influence on the sorption potential.

Fluorescent Dyes↗
PubMed2000

Telomerase activity and telomere length in acute and chronic leukemia, pre- and post-ex vivo culture.

We studied telomerase regulation and telomere length in hematopoietic progenitor cells from peripheral blood and bone marrow from patients with acute and chronic leukemia and myeloproliferative diseases. CD34+ cells from a total of 93 patients with either acute myeloid leukemia (AML; n = 25), chronic myeloid leukemia (CML; n = 21), chronic lymphocytic leukemia (CLL; n = 18), polycythemia vera (PV; n = 16), or myelodysplastic syndromes (MDS; n = 13) were analyzed before and in 19 patients after ex vivo expansion in the presence of multiple cytokines (kit ligand, interleukin-3, interleukin-6, and granulocyte colony-stimulating factor plus erythropoietin). Compared with hematopoietic progenitor cells from normal donors (n = 108), telomerase activity (TA) was increased 2- to 5-fold in chronic phase (CP)-CML, CLL, PV, and MDS. In AML, accelerated phase (AP) and blastic phase (BP)-CML, basal TA was 10- to 50-fold higher than normal. TA of CP-CML CD34+ cells was up-regulated within 72 h of ex vivo culture, peaked after 1 week, and decreased below detection after 2 weeks. In contrast, TA in AP/BP-CML and AML CD34+ cells was down-regulated after 1 week of culture and decreased further thereafter. The expansion potential of CD34+ cells from patients with leukemia was considerably decreased compared with CD34+ cells from normal donors. The average expansion of cells from leukemic individuals was 6.5-, 2.3-, 0.6-, and 0.2-fold in weeks 1, 2, 3, and 4, respectively, whereas expansion of normal cells was 5- to 15-fold higher. In serial expansion culture, a median telomeric loss of 0.7 kbp was observed during 3-4 weeks of expansion. Our results demonstrate that up-regulation of telomerase is similar in CD34+ cells from CP-CML, CLL, PV, and MDS patients and in normal hematopoietic cells during the first week of culture, whereas in AML and AP/BP-CML, telomerase is high at baseline and down-regulated during expansion culture. High levels of telomerase in leukemic progenitors at baseline may be a feature of both the malignant phenotype and rapid cycling. Telomerase down-regulation during culture of leukemic cells may be due to the decreased expansion potential or repression of normal hematopoiesis, or in AML it may be due to the partial differentiation of AML cells, shown previously to be associated with loss of TA. Telomere shortening during ex vivo expansion correlated with low levels of TA, particularly in chronic leukemic and MDS progenitors where telomerase was insufficient to protect against telomere bp loss during intense proliferation.

Adolescent↗
PubMed1998

V-myc in a simple, single gene retroviral vector causes rapid induction of leukemia and concomitant apoptosis following bone marrow transplantation.

We have previously developed an in vivo model of leukemogenesis utilizing mice reconstituted with genetically modified bone marrow cells. Based on those studies, a new single gene retroviral vector has been engineered which efficiently transfers v-myc into immature murine bone marrow cells. All reconstituted mice developed leukemia with a short latency period (5-11 weeks). In addition to hyperproliferation associated with elevated levels of PCNA, extensive apoptosis was also observed in all leukemic animals with p53 accumulating in the apoptotic cells. Whereas bax encoded protein, an effector of p53 apoptotic activity was detected in apoptotic cells, p21Waf1 protein, a potential mediator of p53 growth suppression was not detected in these cells suggesting that v-myc-induced apoptosis was independent of the ability of p53 to induce p21Waf1. These results indicate that apoptosis, a part of the cellular response to v-myc expression, does not prevent leukemia development and that hyperproliferation rather than abrogation of oncogene-induced apoptosis appears to be a critical event in v-myc-induced leukemia.

Animals↗
PubMed1997

Estradiol stimulates growth hormone production in female goldfish.

The effects of estradiol (E2) on growth hormone (GH) production was investigated in gonad-intact female goldfish. It was first necessary to generate a specific antibody for use in immunocytochemistry, Western, and dot-blot analyses of GH production. To accomplish this, grass carp GH (gcGH) cDNA was cloned by the reverse transcription polymerase chain reaction (RT-PCR) and expressed in Echerichia coli and a specific polyclonal antibody to recombinant gcGH was generated in the rabbit. In Western blot, the anti-gcGH antibody specifically immunoreacted with recombinant gcGH, purified natural common carp GH, and with a single 21.5-kDa GH form from pituitary extracts of grass carp, common carp, goldfish, and zebrafish but not salmon, trout, or tilapia. Intraperitoneal injection of the recombinant gcGH enhanced the growth rates of juvenile common carp demonstrating biological activity of this GH preparation. Electron microscopic studies showed that the anti-gcGH-I antibody specifically reacted with GH localized in the secretory granules of the goldfish somatotroph. Using anti-gcGH-I in a dot-blot assay, it was found that in vivo implantation of solid silastic pellets containing E2, (100 micrograms/g body weight for 5 days) increased pituitary GH content by 150% in female goldfish. In a second, independent study employing a previously characterized anticommon carp GH antibody for radioimmunoassay, it was found that E2 increased pituitary GH content by 170% and serum GH levels by approximately 350%. The E2-induced hypersecretion of GH and increase in pituitary GH levels was not associated with changes in steady-state pituitary GH mRNA levels, suggesting that this sex steroid may enhance GH synthesis at the posttranscriptional or translational level. Previous observations indicate that GH can stimulate ovarian E2 production. The present results show that E2 can in turn stimulate GH production, indicating the existence of a novel pituitary GH-ovarian feedback system in goldfish.

Animals↗
PubMed1997

Patient-reported problems associated with dysphonia.

In the UK there has been little assessment of the efficacy of therapy for patients with dysphonia. Current objective assessment methods (e.g. acoustical analysis) do not correlate well with patient symptoms. Existing subjective measures are based on clinical impression. To date, no measure has been based on the patient's experience and the aim of this study was to explore the difficulties that patients encounter as a consequence of their illness or disability. One hundred and thirty-three dysphonic patients completed an open-ended questionnaire where they were asked to make a list of the problems they experienced due to their voice disorder. Responses were categorized using the WHO International Classification of Impairments, Disabilities and Handicaps. A total number of 467 problems were listed: 60% impairments, 26% disabilities and 14% were handicap related. The six major impairments related to altered voice and throat symptoms. Although the majority of disabilities resulted from lack of projection and clarity, the most frequently reported was singing. Reported handicaps encompassed psychological, emotional and employment-related difficulties and effects on family and friends. People with dysphonia experience social, lifestyle and employment difficulties as a consequence of their voice disorder. Responses to the open-ended questionnaire have considerable practical applications in targeting more comprehensive treatment strategies.

Adolescent↗
PubMed1995

The effects of deinstitutionalization on adults with learning disabilities.

We compared a group of people with learning disabilities who have been deinstitutionalized with a control group remaining in an institution on measures of adaptive and maladaptive behaviour, community living skills, social skills, and quality of life. In general, there was no change over 30 months for the control group. Changes for the experimental group were either not seen or were generally modest in scale, and tended to occur within 6 months of moving, the measures staying relatively stable thereafter. Implications for detailed examination of the effects of deinstitutionalization were discussed.

Activities of Daily Living↗
PubMed1994

The p53 status of cultured human premalignant oral keratinocytes.

Around 60% of oral squamous cell carcinomas (SCCs) have been shown to harbour p53 mutations, and other studies have demonstrated mutant p53 genes in normal and dysplastic squamous epithelium adjacent to these SCCs. In line with these earlier studies we show here that DOK, a keratinocyte cell line derived from a dysplasia, displays elevated levels of p53 protein and harbours a 12 bp in-frame deletion of the p53 gene spanning codons 188-191. In contrast, the coding region of the p53 gene was normal in a series of six benign recurrent laryngeal papillomas and a series of four premalignant oral erythroplakia biopsies and their cell cultures. All but one of these lesions were free of malignancy at the time of biopsy, in contrast to the premalignant lesions studied by previous investigators, but keratinocytes cultured from these lesions all displayed a partially transformed phenotype that was less pronounced than that of DOK. Since three out of four of the erythroplakia patients developed SCC within 1 year of biopsy, these lesions were by definition premalignant. The availability of strains of partially transformed keratinocytes from premalignant erythroplakias which possess normal p53 genes should enable us to test the role of mutant p53 in the progression of erythroplakia to SCC. The premalignant tissues and cultures were also tested for the presence of human papillomavirus (HPV), which is known to inactivate p53 function in some cases. Only the benign papillomas were shown to contain high levels of either HPV 6 or HPV 11 E6 DNA, but not both, and none of the samples contained detectable levels of HPV 16, HPV 18 or HPV 33 E6 DNA or L1 DNA of several other HPV types. There was therefore no evidence to suggest that p53 was being inactivated by a highly oncogenic HPV in these samples.

Biopsy↗
PubMed1992

Clinical role of free-field voice tests in children.

Clinical voice testing forms part of the routine assessment of children's hearing. However, its role in paediatric practice has not been defined. In particular, the sensitivity and specificity of the test in detecting the presence of a hearing impairment is not known. The value of the test as a screen was assessed by comparison of the results of free-field clinical voice testing with pure-tone audiometric thresholds in 141 children aged 5-12 years. In order to pass the screen, a child had to respond to a whispered voice 2 feet (60 cm) from the test ear. The mean pure-tone average (average at 0.5, 1.0 and 2.0 kHz) of those ears that passed was 14 dB HL compared with 31 dB HL for those that failed (P less than 0.001). The test was 80% sensitive (95% specific) in detecting a hearing impairment greater than or equal to 25 dB HL, and 89% sensitive (90% specific) in detecting a hearing impairment greater than or equal to 30 dB HL. Therefore, clinical voice tests will fail to detect a significant proportion of children with a hearing impairment and cannot be advocated as a screening method. The test would appear to be of limited value in a specialist situation where facilities for pure-tone audiometry exist.

Age Factors↗
PubMed1992

Multiple primary malignant tumours in patients with head and neck cancer: the implications for follow-up.

The pattern of second primary cancer occurrence in 518 Scottish patients with head and neck cancer was determined by a retrospective study. The overall incidence of second cancers was 9% but the true incidence increased steadily in the years following initial diagnosis to reach a maximum of 21% at 11 years. After 4 years of follow-up patients were more likely to die from a second primary cancer than from the effects of the initial tumour. The Scottish cohort differed from previously reported, overseas, study groups in having a high incidence of second primary cancers in sites outside the upper aerodigestive tract. This potential demographic difference suggests a need for local audit prior to design and implementation of screening protocols for second primary cancers.

Adolescent↗
PubMed1992

Structure of the 5S rRNA genes in birch (Betula papyrifera) and alder (Alnus incana).

Hybridization of a 5S rDNA probe to Southern transfers of birch (Betula papyrifera) or alder (Alnus incana) DNA digested with BamH1 reveals similar triple-band "ladder-like" patterns. The sizes of sequenced 5S repeat units from both plants ranges only from 471 to 490 base pairs, suggesting that the complexity detected by Southern analysis is not due to different size classes of 5S repeats as found in other species. Within the intercistronic spacer region, conservation of large blocks of sequence between birch and alder 5S is observed implying a close evolutionary relationship between these two species. In both species, a duplication of part of the coding sequence including a restriction site for BamH1 introduces a second BamH1 site into the repeat unit. Differential methylation of the two BamHI restriction sites can account for the observed triple-band pattern.

Base Sequence↗
PubMed1990

The resonance frequency of the external auditory canal in children.

The frequency of the resonance peak of the external auditory canal was measured in 250 children aged 3 to 12 years. The mean resonance peak frequency was greatest in the younger age groups (3089 Hz in 4 year olds, range 2298 to 3763) and then decreased with age until 7, the age at which adult values were reached. Children less than 7 years of age have mean resonance frequencies significantly different from adults, suggesting that the "adult" length of external auditory canal is not reached until the age of 7. This alteration in resonance frequency with age may have practical implications by affecting the insertion gain of hearing aid systems in children.

Acoustics↗