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Biomedical subjects

A M Russell

Publications and source records attributed to A M Russell.

At least 19 recordsLinked to original sources
PubMed2006

BRCA1 dysfunction in sporadic basal-like breast cancer.

Basal-like breast cancers form a distinct subtype of breast cancer characterized by the expression of markers expressed in normal basal/myoepithelial cells. Breast cancers arising in carriers of germline BRCA1 mutations are predominately of basal-like type, suggesting that BRCA1 dysfunction may play a role in the pathogenesis of sporadic basal-like cancers. We analysed 37 sporadic breast cancers expressing the basal marker cytokeratin 5/6, and age- and grade-matched controls, for downregulation of BRCA1. Although BRCA1 promoter methylation was no more common in basal-like cancers (basal 14% vs controls 11%, P=0.72), BRCA1 messenger RNA expression was twofold lower in basal-like breast cancers compared to matched controls (P=0.008). ID4, a negative regulator of BRCA1, was expressed at 9.1-fold higher levels in basal-like breast cancer (P<0.0001), suggesting a potential mechanism of BRCA1 downregulation. BRCA1 downregulation correlated with the presence of multiple basal markers, revealing heterogeneity in the basal-like phenotype. Finally, we found that 63% of metaplastic breast cancers, a rare type of basal-like cancers, had BRCA1 methylation, in comparison to 12% of controls (P<0.0001). The high prevalence of BRCA1 dysfunction identified in this study could be exploited in the development of novel approaches to targeted treatment of basal-like breast cancer.

BRCA1 Protein↗
PubMed2004

Exclusion of an extracolonic disease modifier locus on chromosome 1p33-36 in a large Swiss familial adenomatous polyposis kindred.

Familial adenomatous polyposis (FAP), an autosomal dominantly inherited colorectal cancer predisposition syndrome, displays considerable inter- and intrafamilial phenotypic heterogeneity, which represents a major problem in genetic counselling of APC mutation carriers. The Min mouse model indicated a putative disease modifier locus on chromosome 4, which is syntenic to human chromosome 1p35-36. This finding was subsequently supported by parametric and nonparametric linkage analyses in FAP families, however, without identifying functional variants in candidate genes. Recently, germline mutations in the base-excision repair gene MYH (1p33-34) have been described in patients with multiple adenomas, pointing to a possible role as disease modifier in FAP. Here, we present critical reassessment of one of the largest FAP kindreds published, which was previously used in linkage mapping of 1p35-36. In this family, all affected members harbour the same APC germline mutation (5945delA), but display marked phenotypic variability, in particular regarding the occurrence of extracolonic disease that segregates in several branches of the family tree. Using updated clinical information, additional mutation carriers and polymorphic markers, fine mapping of the critical region as well as mutation analysis of the MYH gene were performed. These investigations allowed us to significantly exclude (i) the 1p33-36 region as a modifier locus and (ii) MYH as a modifier gene for extracolonic disease in this FAP kindred. Our results do not eliminate 1p33-36 from suspicion in other families, but clearly indicate that in our family linkage analysis of further putative candidate regions is necessary to identify a disease modifier locus in FAP.

Adenomatous Polyposis Coli↗
PubMed1997

Protecting the integrity of clinical laboratory test results.

The authors' inspection reports demonstrate that the improper alteration of patient data is not a rare aberration in private commercial clinical laboratories. Although laboratory surveyors could be trained to recognize this problem, the availability of unprotected test systems makes even trained inspectors ineffectual. Both regulatory agencies and professional accrediting agencies should be concerned that their surveyors may be placing a seal of approval on what are, in reality, compromised or even fabricated data. In proposing the regulations discussed in this paper, the FDA sought to "preserve the integrity of the agency's enforcement process." This goal will remain unattainable, however, until a mechanism has been devised to secure the original raw data produced by all of the analytical systems being used not only in clinical laboratories but also in environmental laboratories, pharmaceutical laboratories, etc. Laboratories, as well as regulatory agencies and accrediting bodies, need to be concerned on behalf of the patient, but laboratories may also need to be concerned on their own behalf. In the coming era of unprecedented cost constraints and competitive bidding, unscrupulous testing facilities or groups of such facilities could have a significant edge over their conscientious competitors if the issues raised here continue to be ignored. Although the analytical data management systems provide tremendous benefits, some have serious problems in ensuring the security of their data. However, if regulatory agencies, accrediting bodies, professional organizations, and the analyzer vendors make a united commitment, the problem of securing the integrity of analytical data could eventually be resolved. It is hoped that such a commitment will be made in the near future.

Autoanalysis↗
PubMed1986

The association between lameness and fertility in dairy cows.

One thousand, four hundred and ninety-one lactations in 770 Friesian, Holstein and Ayrshire crossbred cows have been used to study the associations between lameness and fertility. Lameness was associated with a longer interval between calving and first service and a longer interval between calving and conception. The largest increases in these intervals, of 17 and 30 days, respectively, occurred in cows with either sole or white line lesions occurring between 36 and 70 days after calving. The conception rate during the 63 days before a diagnosis of lameness was made was lower (31 per cent) than at other times (40 per cent).

Animals↗
PubMed1986

Effect of wet weather on lameness in dairy cattle.

The incidence of lameness in cows recorded by five veterinary practices over one year and one practice over four years was plotted with rainfall and potential soil moisture deficit. Correlation coefficients calculated between lameness, rainfall and potential soil moisture deficit over two-week periods showed the incidence of lameness in summer to be significantly related to the potential soil moisture deficit in the same two-week period and rainfall in the previous two-week period. Differences in patterns of lameness incidence among practices and years were also partly explained by differences in rainfall and potential soil moisture deficit; however, these effects were small compared with those of other factors that affect lameness incidence such as herd size, age and stage of lactation.

Animals↗
PubMed1986

Short-term associations between disease and milk yield of dairy cows.

Short-term associations between disease and milk yield were studied in 1594 lactations occurring between 1977 and 1982 in 732 Friesian, Ayrshire and Holstein crossbred cows. Statistically significant differences in milk yield between one week before and one week after clinical diagnosis were observed for ketosis (5.1 kg/d), hypomagnesaemia (4.1 kg/d), mastitis occurring after peak yield (2.1 kg/d) and lameness (1.1 kg/d). Milk yield declined for as much as 2-4 weeks before diagnosis of disease, and total losses in milk yield associated with ketosis or hypomagnesaemia were estimated to be 60-70 kg. No significant differences were found for endometritis or for mastitis when it occurred before peak yield. Milk yield was suppressed for about 4 weeks after calvings with retained placenta, but there were no corresponding effects of dystocia or hypocalcaemia on milk yield. It is suggested that if automatic daily milk recording is available it may be possible to detect deviations from normal, and hence detect subclinical disease 2 or more weeks before its clinical appearance.

Animals↗
PubMed1985

Effects of stage of lactation, month, age, origin and heart girth on lameness in dairy cattle.

Lameness in herds during one year was commonest in the first month of lactation (15 per cent of all cases). Leg lesions were particularly common at this time (24 per cent of all cases of leg lesions) but white line abscess and sole ulcer were more common a month later. Foul-in-the-foot was one of the two most common lesions at all stages of pregnancy and lactation, and white line abscess the most common (20 per cent of all lesions) in late lactation. Both sole ulcer and underrun heel had lower incidence in the second half of the year than the first. White line abscess was particularly common in March and November although there were significant interactions between month and veterinary practice; foul-in-the-foot was most common in October. Susceptibility to lameness increased with age; 10-year-old cows were over four times more likely to develop lameness than three-year-old cows. This was due particularly to increased incidence with age of white line abscess and sole ulcer and, to a lesser extent, underrun heel. In contrast, foul-in-the-foot and leg lesions showed little change with age. Whereas these lesions accounted for 68 per cent of the total in cows up to two years old, they accounted for only 15 per cent of all lesions in cows over 10 years old. White line abscess was slightly commoner in cows with large heart girths.

Age Factors↗
PubMed1983

Effects of season, herd size, management system and veterinary practice on the lameness incidence in dairy cattle.

The incidence of lameness in herds visited by veterinary practitioners in winter (0.87 cases per 100 cows per month) was greater than in summer (0.71 cases per 100 cows per month). The relative proportions of leg lesions and underrun heel were higher, and those of foul-in-the-foot, interdigital hyperplasia and foreign body in the sole were lower in winter than in summer. In winter, leg lesions and aseptic laminitis were most common in cows housed in cowsheds, white line abscess in cows in strawyards and sole ulcer in cows in either cowsheds or cubicles with concrete yards. The overall incidence of lesions was lower in strawyard accommodation (0.71 cases per 100 cows per month) than in cubicles with yards (0.93 cases per 100 cows per month). Veterinary practitioners saw proportionally fewer cases of foul-in-the-foot but proportionally more cases of sole ulcer in larger than in smaller herds. The animal incidence of lameness ranged from 1.7 to 11.4 per cent among practices; in 20 practices which recorded a total of at least 100 lesions in both summer and winter there was a large variation in the proportions observed of each lesion. A principal component analysis contrasted those practices which tended to see mainly cases of white line abscess, white line separation, foul-in-the-foot and leg lesions with those which saw mainly cases of underrun heel, interdigital hyperplasia, punctured sole with pus and sole ulcer. Twenty-nine per cent of cases of underrun heel and 22 per cent of cases of both deep sepsis and interdigital hyperplasia occurred in conjunction with another lesion.

Animals↗
PubMed1983

Use of COSREEL clinical codes in large animal veterinary practice.

COSREEL, a computerised animal health recording system with a versatile coding system for recording diagnoses, symptoms and medical and surgical treatments, has been tested by veterinary surgeons in practice. The codes were found to be logical and generally easy to use. The application of these codes, with particular reference to their use in infertility investigations, is illustrated.

Animals↗
PubMed1983

Use of COSREEL, a computerised recording system, for herd health management of two dairy herds.

COSREEL, a computerised animal health recording system, has been used since October 1980 by two agricultural colleges for the management of their dairy herds. Each college and the veterinary practice which served the college has had its own typewriter terminal connected to a remote computer. Management and milk data have been coded and entered at the college and clinical data at the veterinary practice. An average of just over one management and veterinary event per week has been coded for every three cows in milk. Error rates were on average 11 per cent by one pair of users and 4 per cent by the other pair. COSREEL has provided a valuable aid to the management of the health of the two herds, and the regular use of pregnancy diagnosis, infertility investigation and oestrus detection action lists resulted in a considerable improvement in herd fertility at the two colleges.

Animal Husbandry↗
PubMed1983

COSREEL: computerised recording system for herd health information management.

COSREEL (Computer System for Recording Events affecting Economically important Livestock) is an animal health recording system which has been designed for the management of cattle, sheep and pigs kept at the ARC Institute for Research on Animal Diseases. Unlike other, numerical, coding systems for the recording of disease, COSREEL has a versatile alpha-numeric coding system which can record diagnosis of disease, local and general symptoms, medical and surgical treatment, vaccination and antiserum therapy, therapeutic management changes and tests with their results. The system is used for recording management, veterinary and milk data, and is a terminal based system using a remote computer. Various lists for action are produced for both herd managers and clinicians including weekly reports of the production and fertility status of individual cows, and lists of cows due for pregnancy diagnosis or infertility investigation. This paper describes the general features of COSREEL, gives examples of the way diagnoses are coded and discusses the future potential of such a system for the development of a central data base for epidemiological analysis.

Animals↗
PubMed1982

Survey of lameness in British dairy cattle.

During 1977 a survey was undertaken by practising veterinary surgeons of the incidence of different lesions causing lameness in dairy cattle. Forty-eight veterinary practices participated and they treated 7526 cases of lameness in 1821 herds. The average incidence of lameness among all cows was 5.5 per cent and the annual incidence among practices ranged from 1.8 to 11.8 per cent. Most lesions (88.3 per cent) occurred in the feet; the commonest were foul of the foot (16.7 per cent), white line abscess (15.6 per cent), sole ulcer (13.6 per cent), punctured sole and pus (10.4 per cent) and underrun heel (8.7 per cent). These proportions varied in different parts of the country. Eighty-four per cent of foot lesions occurred in the hind feet and of these lesions 85 per cent occurred in the outer claw; 42 per cent of foot lesions occurred in abnormally shaped claws. The remaining 11.7 per cent of lesions occurred in the legs and trunk, 76 per cent of which occurred in the hindlimb. Trauma was the main cause of leg lesions, which occurred most frequently in the joints and ligaments.

Animals↗
PubMed1976

Manganese metabolism in cows and goats.

When 54MnCl2 was incubated with fresh bovine or caprine serum for 20 h and the serum subjected to electrophoresis at pH 9.5, the 54Mn bound to transferrin and alpha2-macroglobulin in proportions which varied with the temperature of incubation and the temperature of electrophoresis. Between 0 and 37 degrees C, the higher the temperature of incubation the larger the proportion bound to transferrin and the lower the proportion bound to alpha2-macroglobulin. The temperature at which electrophoresis was performed had little effect on the proportion of 54Mn bound to transferrin, but increasing temperature reduced the proportion of 54Mn bound to alpha2-macroglobulin. Mn2+ did not bind to purified transferrin in vitro in the absence of an oxidising agent. In the presence of permanganate, Mn3+ was formed and chelated by transferrin at physiological pH. In fresh serum this oxidation step may be performed by ceruloplasmin or molecular oxygen. Mn2+ was bound reversibly to alpha2-macroglobulin but this protein played no part in the oxidation of divalent manganese and had no effect on the protein binding of trivalent manganese. Manganese in the divalent state, either free as Mn2+ or bound to alpha2-macroglobulin, is removed from blood plasma very efficiently by the liver. However, the manganic-transferrin complex normally found in circulation is not rapidly removed from plasma. The liver can remove large amounts of excess manganous manganese which it presumably excretes; the small essential fraction of the manganese absorbed is oxidised to the trivalent state and bound to transferrin.

Animals↗
PubMed1976

Iron dynamics in the ruminant.

We have compared the plasma clearance rate of radioactive iron in cows both as ferric chloride and as iron specifically bound to transferrin. We have also repeated the transfusion experiment of Dern et al. (Dern, R.J., Monti A. and Glynn, M.F. (1963) J. Lab. Clin. Med. 61,280-291) using goats. The results show that neither non-specificity bound iron (Bates, F.W. and Schlabach, M.R. (1973) J. Biol. Chem. 248, 3228-3232) nor the iron bound to the two different sites in transferrin (Awai, M., Chipman, B. and Brown, E.B. (1975) J. Lab. Clin. Med. 85,769-784) can be identified as distinguishable iron pools by this technique.

Animals↗
PubMed1976

A variant of prothrombin induced in cattle by prolonged administration of warfarin.

Cows on long term Warfarin therapy produce a form of prothrombin which, although it binds to barium citrate, has a low biological activity. Activation experiments on this form of prothrombin show that it is only slowly converted to thrombin in the presence of Ca2+, although the thrombin produced has normal activity. Further experiments show that the Fragment 1 region of the molecule has a reduced calcium binding capacity. The results indicate the existance of a partially carboxylated form of prothrombin.

Animals↗