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Biomedical subjects

I Anderson

Publications and source records attributed to I Anderson.

At least 55 records · Page 3Linked to original sources
PubMed1998

Searching DNA databases for similarities to DNA sequences: when is a match significant?

MOTIVATION: Searching DNA sequences against a DNA database is an essential element of sequence analysis. However, few systematic studies have been carried out to determine when a match between two DNA sequences has biological significance and this is limiting the use that can be made of DNA searching algorithms. RESULTS: A test set of DNA sequences has been constructed consisting of artificially evolved and real sequences. This set has been used to test various database searching algorithms (BLAST, BLAST2, FASTA and Smith-Waterman) on a subset of the EMBL database. The results of this analysis have been used to determine the sensitivity and coverage of all of the algorithms. Guidelines have been produced which can be used to assess the significance of DNA database search results. The Smith-Waterman algorithm was shown to have the best coverage, but the worst sensitivity, whereas the default BLASTN algorithm (word length set to 11) was shown to have good sensitivity, but poor coverage. A sensible compromise between speed, sensitivity and coverage can be obtained using either the FASTA or BLAST (word length set to 6) algorithms. However, analysis of the results also showed that no algorithm works well when the length of the probe sequence is <200 bases. In general, matches can accurately be identified between coding regions of DNA sequences when there is >35% sequence identity between the corresponding proteins. Searching a DNA sequence against a DNA sequence database can, therefore, be a useful tool in sequence analysis. AVAILABILITY: The test sets used are available via anonymous ftp from mbisg2.sbc.man.ac.uk in the directory /pub/cabios/testdata/ CONTACT: I.Anderson@stud.man.ac.uk; abrass@man.ac.uk

Algorithms↗
PubMed1998

The Center for Epidemiological Studies Depression Scale in older community samples in Indonesia, North Korea, Myanmar, Sri Lanka, and Thailand.

Cultural differences in the reporting of depressive symptoms among older people were examined using the Center for Epidemiological Studies Depression (CES-D) scale in five Southeast Asian countries: Indonesia, Korea, Myanmar, Sri Lanka, and Thailand. Previous work in Asian samples--principally North American immigrants--suggested differential functioning of the CES-D. The four-factor solution established in the original studies of the CES-D was replicated for all countries using a confirmatory factor analytic approach. It was, however, demonstrated that little information was lost in considering full-scale scores rather than the four subscales separately. The behavior of the CES-D in older Asian populations was found to be comparable to results obtained in North American and European cultures. Significant somatization of depression in these Asian samples was not found. There appears to be a general factor measuring depressed mood across older populations. The results support the validity of comparing responses on the CES-D across cultures.

Affect↗
PubMed1998

Data for diagnosis, monitoring and treatment in indigenous health: the case of cervical cancer.

Deficiencies in the availability and quality of data on the health status of indigenous Australians have long been recognised. For cervical cancer, data demonstrate a 2-5 fold greater incidence rate and an 8-10 fold greater mortality rate for Indigenous women compared to non-Indigenous Australians. However, incidence and mortality data are only available for some states and there is little or no information available on the geographic or social distribution of risk, or the reasons for risk differentials. There are also little or no data on the utilisation of, or preferences for, screening services. Thus, while there is clearly a need for a cervical cancer control program specifically to target Indigenous women, current data are inadequate to inform planning and implementation, and current systems are inadequate to monitor effectiveness. This situation is the result of insufficient research and inadequate attention to recording of Indigenous status in routine data systems and applies to a greater or lesser extent across the spectrum of health of Indigenous Australians. Health workers across the spectrum in mainstream and Indigenous medical services have a shared responsibility for improving the availability and quality of data and ensuring the appropriate use of information necessary to achieve and monitor improvements in service delivery and health status of Indigenous people.

Australia↗
PubMed1997

Two populations of the estrogen receptor separated and characterized using aqueous two-phase partitioning.

Two populations of the rat uterine estrogen receptor (ER) were separated and characterized using aqueous two-phase partitioning. Countercurrent distribution of rat uterine cytosolic ER allowed rapid and efficient separation of two populations, one population partitioned preferentially into the top phase (T, K(obs) = 3-6) and the other into the bottom phase (B, K(obs) = 0.01-0.03). The majority of unoccupied cytosolic ER is in the T population. Upon estrogen binding and/or heating to 30 degrees C in vitro the T population is converted to the B population. The transition from T to B does not exclusively involve loss of heat shock protein 90 and does not alter the ligand binding ability of the steroid binding domain. Using the human ER steroid binding domain overproduced in Escherichia coli and the steroid binding domain generated by partial trypsinization of the rat uterine ER, we demonstrate that the characteristic distinguishing T and B populations is not localized to this domain alone but may be associated with the amino terminal half of the ER (the A/B and DNA binding domains). The T to B transition of the ER also occurs in human MCF-7 breast cancer cells upon treatment with estrogen at 37 degrees C.

Animals↗
PubMed1997

Identification of the complete coding sequence and genomic organization of the Treacher Collins syndrome gene.

Treacher Collins syndrome (TCS) is an autosomal dominant disorder of craniofacial development, the features of which include conductive hearing loss and cleft palate. Recently, the demonstration of a series of 10 mutations within a partial-length cDNA clone have indicated that the TCS gene (TCOF1) has been positionally cloned. Although it has been shown that the gene is expressed in a wide variety of fetal and adult tissues, database sequence comparisons have failed to provide significant information on the function of the gene. In the current investigation, a combination of cDNA library screening and rapid amplification of cDNA ends has permitted the isolation of the complete coding sequence of TCOF1, which is encoded by 26 exons and predicts a low complexity, serine/alanine-rich protein of approximately 144 kD. The use of a variety of bioinformatics tools has resulted in the identification of repeated units within the gene, each of which maps onto an individual exon. The predicted protein Treacle contains numerous potential phosphorylaiton sites, a number of which map to similar positions within the repeated units, and shows weak but significant homology to the nucleolar phosphoproteins. Although the precise function of Treacle remains unknown, these observations suggest that phosphorylation may be important for its role in early embryonic development and that it may play a role in nucleolar-cytoplasmic shuttling. The information presented in this study will allow continued mutation analysis in families with a history of TCS and should facilitate continued experimentation to shed further light on the function of the gene/protein during development of the craniofacial complex.

Amino Acid Sequence↗
PubMed1997

Teacher accuracy in the identification of pre-school pupils with hearing loss.

Teachers of 110 pre-school pupils used a questionnaire to identify which children they thought would fail a hearing screening. Following screening, the data was compared to both audiometric only, and combined audiometric and tymponometric screening results. Teachers identified one out of six pupils who failed audiometric screening, and one out of seven who failed combined screening. We concluded that teachers could not accurately identify pupils with hearing problems and should not be used to detect hearing losses in pupils without prior education and training.

Acoustic Impedance Tests↗
PubMed1996

Salmonella septic arthritis of the shoulder in Zambian children.

Nineteen children under the age of two with salmonella septic arthritis (SSA) of the shoulder presented to Mukinge Hospital between 1st January 1992 and 31st March 1993. There were 13 boys and six girls. All patients were below the 50th centile for weight. The most common presentation was swelling, pyrexia and non-use of the arm. Pain was not always present. All patients were anaemic but in many cases had both WBC and ESR in the normal range. All patients were treated with drainage and antibiotics. All made a good recovery and were discharged pain free, apyrexial and using the affected arm. One patient was re-admitted because of recurrent infection. Nine patients reviewed after one month had continued good function with no clinical sign of infection. We conclude that where intestinal salmonella are endemic, low nutritional status is likely to be a factor in the development of a bacteraemia, and that the intra-articular extension of the proximal humeral metaphysis and repetitive minor trauma to the joint are predisposing factors to the development of shoulder infection.

Arthritis, Infectious↗
PubMed1995

Salmonella septic arthritis in Zambian children.

Thirty-four children under the age of 3 years with septic arthritis presented to Mukinge Hospital between 1 January 1992 and 31 March 1993. Twenty-six of these cultured Salmonella spp. The salmonella group comprised 17 males and 9 females with an average age of 10 months. Most patients were anaemic and all were under 50th centile for weight. The commonest presentation was swelling, pyrexia and non-use of the limb. The mean white cell count (WBC) was 14,000/mm3 and the mean erythrocyte sedimentation rate (ESR) was 15.8 mm/h, but in many cases both the WBC and ESR were normal. All patients were treated with drainage and antibiotics. All made a good recovery and were discharged pain free, apyrexial and using the affected joint. One patient was readmitted because of recurrent infection. Nine patients reviewed after 1 month had continued good function. We consider that malnutrition and local trauma are predisposing factors to the development of salmonella septic arthritis in a population where salmonella is endemic.

Arthritis, Infectious↗
PubMed1994

The proximal promoter of the bovine luteinizing hormone beta-subunit gene confers gonadotrope-specific expression and regulation by gonadotropin-releasing hormone, testosterone, and 17 beta-estradiol in transgenic mice.

Transient transfection studies have proven useful in unraveling the molecular mechanisms underlying gonadotrope-specific expression and hormonal regulation of the gene encoding the alpha-subunit of the glycoprotein hormones. In contrast, similar studies performed with the LH beta gene have been less informative. When assayed by transient transfection into alpha T3-1 cells, activity of a 776-basepair bovine LH beta promoter-chloramphenicol acetyltransferase fusion gene (bLH beta CAT) was no greater than that of a promoterless control. To determine whether limited activity in vitro reflected the absence of critical regulatory elements, we examined activity of bovine LH beta fusion genes after stable integration in transgenic mice. In contrast to transient transfection studies, the LH beta promoter targeted high levels of CAT expression specifically to the pituitary. In addition, a bLH beta TK fusion gene was active only in gonadotropes. The bLH beta CAT transgene was also evaluated for responsiveness to gonadal steroids and GnRH. Testosterone and 17 beta-estradiol were capable of suppressing activity 70-80% in castrated males, despite the absence of high affinity binding sites for androgen or estrogen receptors. This suggests that feedback inhibition of LH beta CAT transgene expression by gonadal steroids may occur through an indirect mechanism, possibly at the level of the hypothalamus. To address whether the bLH beta CAT transgene could be regulated by GnRH, we treated ovariectomized females with antide, a GnRH antagonist. Antide suppressed transgene activity by 60%. Thus, the proximal promoter of the bovine LH beta subunit gene directs appropriate patterns of cell-specific expression and retains responsiveness to gonadal steroids and GnRH. In light of the robust activity of the LH beta promoter in transgenic mice, we suggest that this animal model can be exploited further to dissect the complex mechanisms that underlie gonadotrope-specific expression and hormonal regulation of the LH beta gene.

Animals↗
PubMed1993

Structural characterization of the trypsinized estrogen receptor.

Structural differences between the unoccupied and ligand-occupied rat uterine estrogen receptors (ERs) were investigated using partial proteolysis followed by immunoblotting, affinity labeling, and gel filtration chromatography. Trypsin digestion of the unoccupied ER at 4 degrees C resulted in retention of 70-80% of high-affinity [3H]estradiol binding. Only two fragments of the rat ER were detected after prolonged trypsin treatment of the unoccupied ER followed by affinity labeling with [3H]tamoxifen aziridine. One fragment represents the intact steroid binding domain (28 kDa), and the other fragment is about 10 kDa. The small 10-kDa fragment of the ER detected by denaturing gel electrophoresis is shown to be held in a large oligomeric complex in solution using gel filtration chromatography. This oligomeric complex probably represents the steroid binding domain, which has its tertiary structure maintained predominantly by noncovalent interactions between the trypsin-generated fragments. The estrogen, anti-estrogen, and unoccupied trypsinized ERs all result in similar patterns of fragments after separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and detection by immunoblotting. Although no new trypsin cleavage sites were exposed, the sensitivity of the available trypsin sites was altered by heating the ER and, to a lesser extent, by hormone treatment. Gel filtration chromatography of the trypsinized estradiol- and 4-hydroxytamoxifen-occupied ERs demonstrates similar, diffuse peaks centered at about the correct size for the intact steroid binding domain (28 kDa), whereas the trypsinized unoccupied ER results in a sharp, discrete peak centered at about 80 kDa.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗