Familial risk and genetic susceptibility for breast cancer

Clinical observations suggest that breast cancer is occasionallyinherited as an autosomal dominant disease in families. Epidemiologic studies consistently have shown that a history of breast cancer in a first-degree relative increases a woman's risk of breast cancer when compared with the general population. The risk is similar if a mother or sister is affected and is increased further if both are affected. The difficulty with such an observation is that in itself it does not clarify the nature of the true underlying risk factors which could be genetic or due to the aggregation of environmental risk factors in families. Complex segregation analysis of breast cancer aggregation in families suggests that breast cancer susceptibility is due to an autosomal dominant inheritance of one or more rare genes in a few families in which carriers have a high probability of developing the disease perhaps as great as 100 percent. Close linkage of a breast-cancer-susceptibility gene (BRCA1), between markers of the chromosomal region 17q12-q21 on the long arm of chromosome 17, with breast cancer recently has been reported. Families linked to BRCA1 were more likely to have early onset of breast cancer or have breast and ovarian cancer in the family. It is likely that other genes play a role in the unlinked breastcancer families. Both the epidemiologic and genetic data suggest that breast cancer is a heterogeneous disease.     

A conceptual framework of functional capacity evaluation for occupational therapy in work rehabilitation

Functional capacity evaluation (FCE) is commonly used in work rehabilitation to assess the capacity of the injured worker for return to work. Occupational therapists are major providers of FCE, especially in Australia. Despite a history of involvement in the functional assessment of clients for work, occupational therapy has few theoretical models for work assessment in general, and for FCE in particular. This may account for some of the confusion that exists about the conceptual basis of FCE in occupational therapy practice. This paper presents a framework for FCE that parallels occupational therapy's occupational performance model and the World Health Organisation's International Classification of Functioning, Disability and Health. The framework is used to clarify some of the confusions that exist in FCE research and practice, particularly the issue of measuring a client's function versus impairment. A redefinition of FCE for occupational therapy practice in the work assessment continuum is presented that supports occupational therapy practice and research in the area.     

Oestrogen binding and risk factors for breast cancer

Although women with breast cancer tend to have a greater proportion of their circulating oestradiol non-protein bound and albumin bound, and less SHBG-bound, than controls, it remains uncertain whether this has an aetiological role or is an effect of the tumour. Oestradiol and its binding to serum proteins was investigated: (a) in relation to risk factors for breast cancer in a normal population; (b) in women with proliferative benign breast disease as a risk group for breast cancer, and women with non-proliferative benign breast disease as a low risk group, as well as breast cancer patients. The strongest associations were with body mass index; the greater the body mass the greater the bioavailability of oestradiol. Changes in relation to age at menarche and menopause could have been a function of body mass. An interesting change with age was noted with a fall in bioavailability over the menopausal years. There was no relationship apparent for parity, age at first full term pregnancy, family history or country of birth. Similar differences in oestradiol binding between cases and controls were seen for patients with breast cancer, benign epithelial hyperplasia and fibrocystic disease without proliferative changes, but these were not significant. This study provides limited support for the concept that oestradiol binding has an aetiological role in the development of breast cancer.     

Comparison of radon-daughter-induced effects in repair-proficient and repair-deficient cho cell lines

The radiobiological effects of the radon daughter ²¹²Bi were investigated in the Chinese hamster ovary cell line AA8 and its radiosensitive derivative EM9. EM9 cells rejoin radiation-induced DNA strand breaks more slowly than do AA8 cells. Three endpoints were examined: cell killing, G2-induced chromosome aberration frequency, and mutation induction at the hypoxanthine (guanine) phosphoribosyltransferase (HGPRT) locus. Cells were exposed to the alpha-emitter ²¹²Bi chelated to diethylenetriaminepentaacetic acid (²¹²Bi-DTPA). As expected, ²¹²Bi-DTPA was more effective than X-rays in producing cytotoxicity, chromosome aberrations, and gene mutations. The relative biological effectiveness (RBE) for all three endpoints ranged from about 2 for chromosome aberrations to 4.4 for mutation induction. EM9 was more sensitive than AA8 cells to the cytotoxic and clastogenic effects of both X-rays and ²¹²Bi-DTPA, suggesting that the repair deficiency in EM9 cells affects response to low-and high-linear energy transfer (LET) radiation for these endpoints. There was no significant difference between these two cell lines in their mutagenic response to X-rays and AA8 was slightly more sensitive to the mutagenic effects of alpha radiation. These results suggest that alterations in DNA repair ability may affect response of cells to both low- and high-LET radiation-induced cytotoxicity and clastogenicity, but they appear to have little effect on gene mutation induction.     

Selective distribution of a novel tubulin in the developing and mature rat brain

A monoclonal antibody, G8, was isolated which recognizes a form of tubulin (G8-tubulin) with a novel distribution in the rat brain. Immunoblots of rat brain homogenates and immunohistochemical staining of rat brain sections of various ages with G8 revealed a restricted and developmentally regulated distribution of the G8-tubulin. G8 staining was primarily found in granule cell dendrites in the dentate gyrus, in pyramidal cell apical dendrites in the hippocampus, and in Purkinje cell dendrites in the cerebellum. This pattern was much more selective than that observed with three other anti-tubulin antibodies. Relative abundance of G8-tubulin in the brain increases with age between postnatal day 1 (P1) and adulthood. The results suggest that G8 is specific for a novel tubulin form which shows a characteristic distribution in the rat brain. This distribution may indicate that the G8-tubulin possesses functional specificity.     

Posterior fossa intracranial hemorrhage in infants treated with extracorporeal membrane oxygenation: sonographic findings

Posterior fossa hemorrhage was documented by autopsy in five infants who had been treated with extracorporeal membrane oxygenation over a 5-year-period. In all five cases, the diagnosis was made prospectively by cranial sonography. Sonographic findings were compared with those in a control group of 15 infants with normal posterior fossae at autopsy. The following sonographic abnormalities were exhibited in neonates with posterior fossae hemorrhage: loss of definition of the cerebellum and fourth ventricle on midline sagittal images, heterogeneous cerebellar parenchyma, focal hypoechoic lesions, ventricular dilatation, and tentorial abnormalities. Bright foci inferior to the third ventricle were seen in four neonates in the normal control group. These foci measured 5-10 mm in diameter. One cranial sonogram was falsely interpreted as showing a posterior fossa hemorrhage because of prominent echoes in the interpeduncular cistern. Infants treated with extracorporeal membrane oxygenation are at risk for developing posterior fossa hemorrhage. Awareness of sonographic signs and potential pitfalls in the interpretation of posterior fossa hemorrhage is important for early and accurate recognition of these unusual and sometimes treatable hemorrhages.     

Beyond the rodent model: Calorie restriction in rhesus monkeys

Lifespan extension and reduction of age-related disease by calorie restriction (CR) are among the most consistent findings in gerontological research. The well known effects of CR have been demonstrated many times in rodents and other short-lived species. However, effects of CR on aging in longer-lived species, more closely related to humans, were unknown until recently. Studies of CR and aging using nonhuman primates (rhesus monkeys) were begun several years ago at the National Institute on Aging, the University of Wisconsin-Madison, and the University of Maryland. These studies are beginning to yield useful data regarding the effects of this nutritional intervention in primates. Several studies from these ongoing investigations have shown that rhesus monkeys on CR exhibit physiological responses to CR that parallel findings in rodents. In addition, several potential biomarkers of aging are being evaluated and preliminary findings suggest the possibility that CR in rhesus monkeys could slow the rate of aging and reduce age-related disease, specifically diabetes and cardiovascular disease. It will be several years before conclusive proof that CR slows aging and extends life span in primates is established, however, results from these exciting studies suggest the possibility that the anti-aging effects of CR reported in rodents also occur in longer-lived species such as nonhuman primates, strenghtening the possibility that this nutritional intervention will also prove beneficial in longer-lived species, including humans.