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Acute stroke due to supratentorial intracerebral haemorrhage is associated with high morbidity and mortality. Open craniotomy haematoma evacuation has not been found to have any benefit in large randomised trials. We assessed whether minimally invasive catheter evacuation followed by thrombolysis (MISTIE), with the aim of decreasing clot size to 15 mL or less, would improve functional outcome in patients with intracerebral haemorrhage.

Accurately identifying women at increased risk of developing breast cancer will provide greater opportunity for early detection and prevention. DNA promoter methylation is a promising biomarker for assessing breast cancer risk. Breast milk contains large numbers of exfoliated epithelial cells that are ideal for methylation analyses. Exfoliated epithelial cells were isolated from the milk obtained from each breast of 134 women with a history of a non-proliferative benign breast biopsy (Biopsy Group). Promoter methylation of three tumor suppressor genes, RASSF1, SFRP1and GSTP1, was assessed by pyrosequencing of bisulfite-modified DNA. Methylation scores from the milk of the 134 women in the Biopsy Group were compared to scores from 102 women for whom a breast biopsy was not a recruitment requirement (Reference Group). Mean methylation scores for RASSF1and GSTP1were significantly higher in the Biopsy than in the Reference Group. For all three genes the percentage of outlier scores was greater in the Biopsy than in the Reference Group but reached statistical significance only for GSTP1. A comparison between the biopsied and non-biopsied breasts of the Biopsy Group revealed higher mean methylation and a greater number of outlier scores in the biopsied breast for both SFRP1and RASSF1, but not for GSTP1. This is the first evidence of CpG island methylation in tumor suppressor genes of women who may be at increased risk of developing breast cancer based on having had a prior breast biopsy.

The present study investigates factors mediating odor and social preferences in female house mice (Muc domesticus) based on the t-complex geontype of males. Previous studies in this laboratory showed that females prefer the odors of wild-type (+/+) males over those that carry lethal genes (+/t). The purpose of this study was to determine the genetic, hormonal, and environmental factors that regulate these preferences. The variables examined include t-complex genotype, genetic background, estrous condition of test females (+/+ or +/t), and genotype of the test female's parents. Results indicate that female preferences for +/+ males are dependent upon the t-complex genotype and estrous condition of test females. Only +/t females in estrus showed preferences for +/+ males. Estrous cycle condition effects were seen in both wild (+/+w5) and inbred (129 +/tw5)females. Homozygous females (+/+) and diestrous females of both geno-types did not demonstrate preferences for either +/+ or +/t males.

Twenty-five percent of wild house mice are heterozygous (+/t) for a deleterious, recessive mutation at the t complex. In previous studies we have demonstrated that wild female house mice can discriminate +/+ from +/t males and show strong preferences for the odors of males who do not carry t mutations. In the present study we examine the extent to which preferences of +/+ female mice are influenced by the genotype of their parents and or littermates. Our data indicate that when +/+ females are reared by two +/+ parents, they exhibit strong preferences for the odors of +/+ males. In contrast, when a +/+ female is reared by one +/+ and one +/t parent she shows no preference for males of either genotype. A second experiment using mice carrying recombinant chromosomes indicates that the genes responsible for the parental (or family) odor cue are not the deleterious t mutations per se but rather other genes linked to these mutations.

Wild female house mice have strong preferences for odors of male mice whose t-complex genotype is +/+ rather than for males carrying deleterious mutations (+/t) at the t complex. In this review of a large number of studies examining the basis for this preference, we suggest the following: first, preferences of +/+ females are greatly influenced by environmental factors and probably do not have a large genetic component: second, preferences of +/t females are less dependent upon environmental factors and hence may have a strong genetic component: third, the lethal factors within the t complex are involved in both the production of the cue by males and the expression of the preference in females: and fourth, there may be a second gene or genes within the t complex involved in the expression of female preference.

Male wild house mice (Mus musculus) were given a choice of odors of females whose T-locus genotype was +/ + or +/t. Males showed strong preferences for the odors of +/ + females. However, when males were tested with odors of recombinant females whose genotype differed at the T locus but which carried similar haplotypes at the H-2 locus, the preference for odors of +/+ females was not manifested. Consequently, differences in female odor production that are responsible for male odor preference are not due specifically to the female genotype at the T locus.

Female house mice (Mus musculus), derived from several populations of wild-caught mice, were tested for their ability to discriminate between males whose genotype at the T locus was +/+ and those whose genotype was +/t, using odor cues alone. Females spent more time near the odors or +/+ males than near the odors of +/t males. This preference was independent of the T-locus genotype of the female and the particular type of t allele carried by either the male or the female. A female's preference, however, did appear to be related to the genotype of her parents. Females with one +/t parent were more likely to prefer +/t males than were females whose parents were both +/+. In a second experiment 18 females were tested with odors from soiled bedding of recombinant males whose genotype varied at the T locus but who were similar at the H-2 locus. As a control, these 18 females were also tested with bedding of wild-derived +/+ and +/tw semilethal males. Females tested with recombinant males preferred odors of males not carrying lethal t alleles over those of males carrying two lethal t alleles, indicating that T-locus variability, not H-2-locus variability, is responsible for odor differences between +/+ and +/t males. Female responses to odors of recombinanat males did not differ from those to odors of +/+ and +/tw semilethal males. Responses of mice to odor differences associated with T-locus variability may have evolved independently of responses to odor variability associated with the H-2 locus.

Data obtained from published studies and from mice trapped for use in our laboratory were analyzed to determine the relationship between frequency of t-haplotypes in wild house mice (Mus musculus) and other variables such as sex, age at capture, and kind of t-haplotype found in the population. In addition, the frequency of t-alleles in populations from which mice had been sampled repeatedly was examined to determine whether, within populations, frequency of t-haplotypes tends to change over time. Populations in which semilethal haplotypes predominated had higher frequencies of heterozygous animals than populations in which the predominant haplotype was a lethal. Furthermore, frequencies of t-haplotypes were higher in males than in females. However, no difference in frequency of t-alleles was found between mice trapped as juveniles and individuals of the same sex trapped as adults. Furthermore, only one of 14 populations from which mice were trapped repeatedly showed evidence of a change in frequency of heterozygotes over time. The relevance of these data for potential processes controlling the frequency of t-haplotypes in wild populations is discussed.

This paper reviews work conducted over the last several years on the effect of genetic differences within the t-complex of wild house mice on female mating preference. Wild mice are polymorphic for a mutation within the t complex on chromosome 17. About 25% of wild mice are heterozygous (+/t) for a t-haplotype and the remainder are +/+. These t-haplotypes have a number of deleterious effects when homozygous and hence t/t individuals are rarely found in wild populations. We have examined preferences of +/+ and +/t females for males of both genotypes. We have found that +/t, but not +/+ females have strong preferences for +/+ males. These preferences can be modified by a variety of factors including estrous condition of the female (the preferences are stronger among estrous than diestrous females) and the dominance status of the male (when forced to choose, females give priority to male dominance status over t complex genotype in choosing males). The restiction of preference to +/t females indicates that genes on t haplotypes modulate these preferences. Because t haplotypes include the major histocompatibility complex (MHC) of the mouse we designed a study to ascertain whether the preferences of +/t females were associated with the MHC. Results of the study indicate that the preferences are independent of the MHC. Further work testing females carrying a partial t-haplotype (tw18) indicates that the genes for mating preference are localized in the region of the t complex distal to the MHC. A large number of t haplotypes are found in wild mouse populations. Females that are themselves +/t when forced to choose between 2 +/t males (one carrying a haplotype that is the same as their own and one carrying a haplotype that is different) prefer males carrying t-haplotypes that differ from their own. Finally, we conclude that mating preference may only be a weak force regulating the frequency of t-mutations in wild mouse populations. The impact of mating preference on population genetics of genes within this region is muted because of the great importance of male dominance rank in determining mating patterns within interacting social groups.