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Biomedical subjects

M Cross

Publications and source records attributed to M Cross.

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

Do you Read me?

Explore the source record for details and available documents.

Abstracting and Indexing↗
PubMed1998

Control of VSG gene expression sites in Trypanosoma brucei.

Antigenic variation in African trypanosomes continues to be one of the most elaborate and intriguing strategies ever devised by a protozoan parasite to avoid complete destruction by the immune defense of its mammalian host. Here we review some of the recent advances in our understanding of this strategy, concentrating on (unpublished) work from our laboratory.

Animals↗
PubMed1998

The significance of involved tumour bed biopsy following wide local excision of breast cancer.

AIM: Following wide local excision of breast cancer approximately 25% of patients have residual disease in the tumour bed. The aim of this study was to determine whether positive bed biopsy correlated with either local recurrence or overall survival. METHOD: Following wide excision bed biopsies were taken at four separate sites from the tumour bed. Histopathological assessment of the bed biopsies was made and compared to features within the primary tumour. Patients were followed-up over a median period of 6.17 years and local recurrence and survival data documented. RESULTS: Two hundred and sixty-eight patients were included in the study and 63 had positive bed biopsies. In all, 85 patients had a recurrence of breast cancer and 69 died. Kaplan-Meier plots showed no evidence of a difference in survival between bed biopsy positive and negative patients. Bed biopsy positive patients were at greater risk of local recurrence. CONCLUSIONS: These findings suggest that positive bed biopsy is associated with an increase in local recurrence rates but has no effect on overall survival following wide excision of breast cancer.

Adult↗
PubMed1998

Frequent loss of the active site during variant surface glycoprotein expression site switching in vitro in Trypanosoma brucei.

African trypanosomes undergo antigenic variation of their variant surface glycoprotein (VSG) coat to avoid being killed by their mammalian hosts. The active VSG gene is located in one of many telomeric expression sites. Replacement of the VSG gene in the active site or switching between expression sites can give rise to a new VSG coat. To study Trypanosoma brucei VSG expression site inactivation rather than VSG gene switching, it is useful to have an in vitro negative-selection system independent of the VSG. We have achieved this aim by using a viral thymidine kinase (TK) gene. Following integration of the TK gene downstream of the 221a VSG expression site promoter, transformant cell lines became sensitive to the nucleoside analog 1-(2-deoxy-2-fluoro-8-D-arabinofuranosyl)-5-iodouracil. These TK trypanosomes were able to revert to resistance at a rate approaching 10(-5) per cell per generation. The majority of revertants expressed a new VSG gene even though there had been no selection against the VSG itself. Analysis of these switched variants showed that some had shut down TK expression via an in situ expression site switch. However, most variants had the complete 221 expression site deleted and another VSG expression site activated. We speculate that a new VSG expression site cannot switch on without inactivation of the old site.

Animals↗
PubMed1998

Biosynthesis and function of the modified DNA base beta-D-glucosyl-hydroxymethyluracil in Trypanosoma brucei.

beta-D-Glucosyl-hydroxymethyluracil, also called J, is a modified DNA base conserved among kinetoplastid flagellates. In Trypanosoma brucei, the majority of J is present in repetitive DNA but the partial replacement of thymine by J also correlates with transcriptional repression of the variant surface glycoprotein (VSG) genes in the telomeric VSG gene expression sites. To gain a better understanding of the function of J, we studied its biosynthesis in T. brucei and found that it is made in two steps. In the first step, thymine in DNA is converted into hydroxymethyluracil by an enzyme that recognizes specific DNA sequences and/or structures. In the second step, hydroxymethyluracil is glucosylated by an enzyme that shows no obvious sequence specificity. We identified analogs of thymidine that affect the J content of the T. brucei genome upon incorporation into DNA. These analogs were used to study the function of J in the control of VSG gene expression sites. We found that incorporation of bromodeoxyuridine resulted in a 12-fold decrease in J content and caused a partial derepression of silent VSG gene expression site promoters, suggesting that J might strengthen transcriptional repression. Incorporation of hydroxymethyldeoxyuridine, resulting in a 15-fold increase in the J content, caused a reduction in the occurrence of chromosome breakage events sometimes associated with transcriptional switching between VSG gene expression sites in vitro. We speculate that these effects are mediated by the packaging of J-containing DNA into a condensed chromatin structure.

Animals↗
PubMed1998

Exercise-induced hyperthermia and hormonal responses to exercise.

Changes in plasma hormonal concentrations during exercise have been ascribed to the type, duration, and intensity of exercise, physical fitness of subjects, oxygen availability and debt, and acid-base balance. However, relatively few studies have examined the possible role of exercise-induced hyperthermia. This paper reviews previous studies on this subject and describes a series of experiments carried out in our laboratories to define the role of changes in body temperature in the release of hormones during exercise. In a first series of experiments, we studied the relationship between thermoregulatory and growth hormone responses to severe exercise at 23 degrees C for 2 h in fit euhydrated subjects, controlling the core temperature increase to a maximum of 40 degrees C by varying wind speed. Exponential relationships were found between increases in core temperature and plasma growth hormone, prolactin, and catecholamines during exercise, suggesting the existence of a thermal threshold for stimulation of hormonal release during exercise. The effect of endurance exercise with and without a thermal clamp (immersion in cold and warm water) on hormonal and leukocyte responses was examined. Again, a significant exponential relationship was found between increases in core temperature and hormonal responses. Thermal clamping significantly diminished the hormonal and the leukocytic responses to exercise, suggesting that an exercise-induced thermal threshold of approximately 38 degrees C exists where hormonal responses are observed. Therefore, core temperature increases may be integrated in the controlling system of hormonal and leukocytic responses to exercise.

Body Temperature↗
PubMed1998

Undetected communication problems in children with behavioural problems.

There is an increasing amount of evidence for links between emotional and behavioural problems and communication difficulties. Many children who hav emotional and behavioural problems also have communication difficulties (Cohen and Lipsett 1991, Benaisch et al. 1993) and children who have communication difficulties are more likely to develop psychiatric illness than their peers (Cantwell and Baker 1985). More importantly there are many children with emotional and behavioural problems who have undiagnosed speech and language difficulties. These have been found in child psychiatric populations (Cohen, et al 1993) and special educational settings (Burgess and Bransby 1990). This paper reports on a small-scale study which found undetected communication problems in children looked after by the local authority. The implications for these children are explored.

Adolescent↗
PubMed1998

Going it alone.

A delivery system in Western New York has developed many of its own software programs, saving big bucks. Now, it's buying certain clinical programs and integrating them with the home-grown software.

Cost Control↗
PubMed1998

Mapping. Using specialized software as a competitive tool.

Cost pressures of managed care, consolidation of health care organizations and the need to effectively spend marketing dollars are strengthening demand for geographic information systems. Providers, payers and others are using the software to convert a wide variety of information into easy-to-understand maps and reports.

Catchment Area, Health↗