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Biomedical subjects

T Marshall

Publications and source records attributed to T Marshall.

At least 91 records · Page 5Linked to original sources
PubMed1998

Clinical analysis of human urinary proteins using high resolution electrophoretic methods.

The application of isoelectric focusing (IEF), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), two-dimensional electrophoresis (2-DE) and capillary electrophoresis (CE) for high resolution electrophoretic analysis of human urinary proteins is reviewed. In each case, the information is tabulated chronologically with details of sample preparation, electrophoretic system, detection method and clinical application. The text includes an historical perspective of the use of each method for urinalysis and a detailed review of the application of the methods to the investigation of renal disease, renal transplantation, Bence Jones proteinuria (BJP), diabetes mellitus, cadmium toxicity, nephrolithiasis and cancers of the urogenital tract.

Electrophoresis↗
PubMed1998

Analysis of Bence Jones proteinuria by high resolution two-dimensional electrophoresis.

Analysis of Bence Jones proteinuria by high resolution two-dimensional electrophoresis (2-DE) and immunoblotting reveals a complex pattern of light chain (LC) isoforms corresponding to the free monoclonal Bence Jones protein and its fragments. Replica blotting gives duplicate blots for LC typing (lambda, chi) and, under the conditions employed, leaves sufficient protein for Coomassie Blue staining of the urinary protein profile and pIIMr determination of the LC isoforms. Carrier ampholytes (CAs, in our "simplified" 2-DE system) and immobilised pH gradients (IPGs, in the Multiphor 2-DE system) give similar LC isoform patterns. Artifacts, including cone-like distortions and trailing "piggyback" spots, are visualised with both 2-DE systems. IPGs are advantageous as they allow reproducible detection of strongly basic LC isoforms by isoelectric focusing (under equilibrium conditions) without recourse to CA nonequilibrium pH gradient electrophoresis.

Bence Jones Protein↗
PubMed1998

5-Lipoxygenase reaction products modulate alveolar macrophage phagocytosis of Klebsiella pneumoniae.

The leukotrienes are potent lipid mediators of inflammation formed by the 5-lipoxygenase-catalyzed oxidation of arachidonic acid. Although the effects of leukotrienes on neutrophil chemotaxis and activation have been established, their role in modulating innate host defense mechanisms is poorly understood. In a previous study (M. Bailie, T. Standiford, L. Laichalk, M. Coffey, R. Strieter, and M. Peters-Golden, J. Immunol. 157:5221-5224, 1996), we used 5-lipoxygenase knockout mice to establish a critical role for endogenous leukotrienes in pulmonary clearance and alveolar macrophage phagocytosis of Klebsiella pneumoniae. In the present study, we investigated the role of specific endogenous leukotrienes in phagocytosis of K. pneumoniae and explored the possibility that exogenous leukotrienes could restore phagocytosis in alveolar macrophages with endogenous leukotriene synthesis inhibition and enhance this process in leukotriene-competent cells. Rat alveolar macrophages produced leukotriene B4 (LTB4), LTC4, and 5-hydoxyeicosatetraenoic acid (5-HETE) during the process of phagocytosis, and the inhibition of endogenous leukotriene synthesis with zileuton and MK-886 dramatically attenuated phagocytosis. We also observed a reduction in phagocytosis when we treated alveolar macrophages with antagonists to the plasma membrane receptors for either LTB4, cysteinyl-leukotrienes, or both. In leukotriene-competent cells, LTC4 augmented phagocytosis to the greatest extent, followed by 5-HETE and LTB4. These 5-lipoxygenase reaction products demonstrated similar relative abilities to reconstitute phagocytosis in zileuton-treated rat alveolar macrophages and in alveolar macrophages from 5-lipoxygenase knockout mice. We conclude that endogenous synthesis of all major 5-lipoxygenase reaction products plays an essential role in phagocytosis. The restorative and pharmacologic effects of LTC4, LTB4, and 5-HETE may provide a basis for their exogenous administration as an adjunctive treatment for patients with gram-negative bacterial pneumonia.

Animals↗
PubMed1998

Influence of five years of antenatal screening on the paediatric cystic fibrosis population in one region.

BACKGROUND: Antenatal screening for cystic fibrosis has been endorsed by the US National Institutes of Health. Edinburgh is the only city in the UK with an established routine antenatal screening programme for cystic fibrosis. AIMS: To report the change in numbers of infants diagnosed with cystic fibrosis born in Edinburgh after the introduction of antenatal screening for the disease. POPULATION: Infants diagnosed as having cystic fibrosis (by sweat test or genotyping, or both) in the seven years before antenatal testing (1984-90) and the first five years of antenatal testing (1991-95). Children born in this region who had moved before diagnosis were identified from the UK cystic fibrosis survey database. RESULTS: The incidence of cystic fibrosis decreased from an average of 4.6 to 1.6 children each year with antenatal screening. The reduction in the incidence (65%) was greater than that accounted for by prenatal diagnosis and termination (36%). Of the eight children born with cystic fibrosis during the period of antenatal screening, five had been subject to antenatal screening: three had only one mutation identified, one was missed due to a laboratory error, and one was identified as a one in four risk, but prenatal diagnosis was not performed. CONCLUSIONS: Antenatal testing for cystic fibrosis has successfully reduced the incidence of cystic fibrosis in this region. Although the numbers are small, it is possible that the reduction in numbers may have been greater than might be expected from antenatal screening alone.

Cystic Fibrosis↗
PubMed1998

P67L: a cystic fibrosis allele with mild effects found at high frequency in the Scottish population.

Only three mutant cystic fibrosis (CF) alleles have to date been established as conferring a dominant mild effect on affected subjects who are compound heterozygotes. We now add a fourth, P67L, which occurs on about 1.4% of Scottish CF chromosomes. Among 13 patients (12 unrelated) with this allele, the average age at diagnosis was 22.5 +/- 11.3 years. None of the cases had consistently raised sweat chloride concentrations, the average value being 57 +/- 9 mmol/l; 77% of the patients were pancreatic sufficient. When compared to three other established mild CF alleles, R117H, A455E, and 3849 + 10kb C-T, a compound heterozygote for P67L has minimal disease and clinical suspicions are unlikely to be confirmed other than by DNA typing.

Adolescent↗
PubMed1998

Validation of the heat treatment step used in the production of diaspirin crosslinked hemoglobin (DCLHb) for viral inactivation.

A series of experiments was performed to assess the ability of the heat treatment step used in the manufacture of diaspirin crosslinked hemoglobin (DCLHb) to inactivate viruses. In-process solutions (reaction mixtures after the crosslinking process) from six different manufacturing lots were used as test media in a 1:680 scaled down system in which the key process parameters used in the large scale production were duplicated. The inactivation of five different viruses (Bovine Viral Diarrhea Virus, Pseudorabies Virus, Human Immunodeficiency Virus 1, Porcine Parvovirus and Hepatitis A Virus) was evaluated. Each validation experiment consisted of spiking the solution at 37 degrees C with virus, heating to 74 +/- 1 degrees C over a period of 30 minutes, holding at 74 +/- 1 degrees C for 90 minutes and cooling from 74 +/- 1 degrees C to less than 10 degrees C over a period of 30 minutes. Duplicate experiments were performed with each of the viruses with the exception of Human Immunodeficiency Virus 1, for which three experiments were performed. In each experiment samples were removed before, during, and after heating for the purpose of determining virus titer and evaluating key process parameters. The results obtained from these experiments confirmed that the key process parameters in these experiments using the scaled down test system reproduced those of the large scale manufacturing process. The results of the virus assays showed at least a 7 log reduction was accomplished by the heat treatment for each of the viruses tested.

Animals↗
PubMed1998

A review of tonsillectomy for recurrent throat infection.

Tonsillectomy is most frequently carried out for recurrent throat infection, but there is uncertainty about its effectiveness. This paper reviews the evidence of its effectiveness obtained from a search of the Cochrane database and MEDLINE for randomized controlled trials comparing tonsillectomy with non-surgical management of recurrent throat infection. The results show that the effectiveness of a procedure such as tonsillectomy, needs to be considered in the light of its adverse effects. Attempts should be made to inform patients about the uncertainty surrounding the procedure.

Adolescent↗
PubMed1997

Transcription elongation factor P-TEFb is required for HIV-1 tat transactivation in vitro.

P-TEFb is a key regulator of the process controlling the processivity of RNA polymerase II and possesses a kinase activity that can phosphorylate the carboxy-terminal domain of the largest subunit of RNA polymerase II. Here we report the cloning of the small subunit of Drosophila P-TEFb and the finding that it encodes a Cdc2-related protein kinase. Sequence comparison suggests that a protein with 72% identity, PITALRE, could be the human homolog of the Drosophila protein. Functional homology was suggested by transcriptional analysis of an RNA polymerase II promoter with HeLa nuclear extract depleted of PITALRE. Because the depleted extract lost the ability to produce long DRB-sensitive transcripts and this loss was reversed by the addition of purified Drosophila P-TEFb, we propose that PITALRE is a component of human P-TEFb. In addition, we found that PITALRE associated with the activation domain of HIV-1 Tat, indicating that P-TEFb is a Tat-associated kinase (TAK). An in vitro transcription assay demonstrates that the effect of Tat on transcription elongation requires P-TEFb and suggests that the enhancement of transcriptional processivity by Tat is attributable to enhanced function of P-TEFb on the HIV-1 LTR.

Amino Acid Sequence↗
PubMed1997

Bone mineral density in Turner's syndrome--a longitudinal study.

OBJECTIVE: Osteoporosis is a recognized problem in adult women with Turner's syndrome, the aetiology of which is unclear. The aim of this study was to examine bone mineralization longitudinally in a group of girls with Turner's syndrome and to study the effect of different treatments on bone mineral density. DESIGN: A prospective observational study. PATIENTS: Eighteen girls with Turner's syndrome aged 4-17 years attending a paediatric endocrine clinic. MEASUREMENTS: Bone mineral density of the lumbar spine was assessed using dual energy X-ray absorptiometry at several time points over a 2.5-year period. RESULTS: Only one girl had evidence of a significant reduction in bone density when comparisons were made with control data related to body weight and pubertal status. No advantage was found for any form of treatment in optimizing bone mineralization. CONCLUSIONS: As there is little evidence of reduced bone mineral density in girls with Turner's syndrome there is no justification for an early introduction of oestrogen replacement during the prepubertal years.

Adolescent↗
PubMed1997

Scientific knowledge in medicine: a new clinical epistemology?

Technological developments in the field of communications have widened access to research evidence and, as a result, scientific epistemology is in the ascendancy in the area of medical knowledge. This has been the subject of vigorous debate within the medical profession itself, with many opposing the increasing weight given to research evidence at the expense of expert opinion. Medicine has a professional culture which identifies knowledge with particular individuals - a 'person culture'. Much of the authority of physicians derives from the presumption that medical professionals have privileged access to medical knowledge. Scientific epistemology, on the other hand, identifies knowledge with a process of investigation. The esoteric knowledge to which expert individuals claim privileged access has no currency in this process. Because of this, the rise of scientific epistemology in medicine partially undermines the profession's authority. Access to scientific research evidence can be used to undermine the individual authority of professional experts. Illustrative examples are given of the nature of debate within a 'person culture' and of ways in which research evidence has been used to challenge the authority of physicians.

Attitude of Health Personnel↗
PubMed1997

Asking questions about women's reproductive health: validity and reliability of survey findings from Istanbul.

In countries where population-based data on health problems are scarce, the extent of reproductive morbidity can be estimated from replies in structured interviews as a complement or as an alternative to reports from physician's examination and laboratory tests. We examined the sensitivity and specificity of detected morbidity based on these replies as compared to medical diagnoses and explored the consistency of replies when the questionnaire was administered twice, by two types of interviewers in different environments. Data were collected in a cross-sectional survey in Istanbul. The presence or absence of five morbidities, reproductive and urinary tract infections (RTI and UTI), menstrual disorders, pelvic relaxation and anaemia was determined by algorithms based on the replies, and by the physician's diagnosis. Except with anaemia, questionnaire replies were more specific than sensitive in detecting morbidity, probably partly due to many morbid conditions being accepted as normal. Sepcificity exceeded 80% for home reports of menstrual disorders (93.0%), pelvic relaxation (95.7%), RTI (abnormal discharge and pain) (81.2%) and UTI (80.7%), with the corresponding figure for anaemia at 41.7%; the best sensitivity results were for anaemia (58.3%), RTI (abnormal discharge only) (49.3%) and menstrual disorders (45.4%) with figures for pelvic relaxation and UTI reaching only 17.3 and 13.0%. Reliability between the interviews (assessed by the K coefficient), was highest at 66.1% for pelvic relaxation and lowest at 39.9% for menstrual disorders. Reliability varied between the two lay interviewers, suggesting the interviewer and the interview conditions are important. Questionnaire-based information on this type of morbidity is most useful for ascertaining perceived ill-health and only of limited use for the corresponding medically defined conditions.

Adult↗
PubMed1997

Relationship between CD4 count and CD4% in HIV-infected people.

OBJECTIVE: To describe the relationship between absolute CD4 count and CD4%, and the influence on this of gender, risk group, age, a diagnosis of AIDS, use of zidovudine (ZDV) therapy and PCP prophylaxis. METHODS: 9203 paired serial measurements of CD4 count and CD4% on 1017 initially AIDS-free and ZDV-naive HIV positive patients from a London-based cohort were available for analysis. Multi-level regression procedures were used on log-transformed data to relate values of CD4 count to a given level of CD4%. We estimated the effect of selected covariates on this relationship from the exponent of the covariate coefficient. RESULTS: A strong linear relationship was found between log CD4 and log CD4%, CD4 = e 1.78(CD4%)1.26 or 5.93 (CD4%)1.26 (excluding covariates). Based on this model, a CD4% of 5%, 15%, and 30% corresponded to an estimated CD4 count (95% confidence interval [CI]) of 45 cells/mm3 (17-117 cells/mm3), 182 cells/mm3 (64-499 cells/mm3) and 438 cells/mm3 (132-1395 cells/mm3), respectively. However, after adjustment for selected covariates, the predicted CD4 count for a given CD4% was found to be lower among heterosexuals and injecting drug users as compared with homosexual men by 30% and 17% respectively; following an AIDS diagnosis by 21%; and after initiation of ZDV therapy and PCP prophylaxis by 19% and 10%, respectively. CONCLUSION: This analysis should be useful to clinicians and researchers in relating values of CD4 count to CD4%, although we have demonstrated that this is not a simple relationship. The wide CI observed in the estimated CD4 count particularly at high CD4% values, and the adjustments necessary according to risk group, following an AIDS diagnosis and use of ZDV and PCP therapy limit its application in the clinical setting.

Adolescent↗