Characterization of a novel breast carcinoma xenograft and cell line derived from a BRCA1 germ-line mutation carrier

A human tumor xenograft (L56Br-X1) was established from a breast cancer axillary lymph node metastasis of a 53-year-old woman with a BRCA1 germ-line nonsense mutation (1806C>T; Q563X), and a cell line (L56Br-C1) was subsequently derived from the xenograft. The xenograft carries only the mutant BRCA1 allele and expresses mutant BRCA1 mRNA but no BRCA1 protein as determined by immunoprecipitation or Western blotting. The primary tumor, lymph node metastasis, and xenograft were hypodiploid by DNA flow cytometry, whereas the cell line displayed an aneuploidy apparently developed via polyploidization. Cytogenetic analysis, spectral karyotyping, and comparative genomic hybridization of the cell line revealed a highly complex karyotype with numerous unbalanced translocations. The xenograft and cell line had retained a somatic TP53 missense mutation (S215I) originating from the primary tumors, as well as a lack of immunohistochemically detectable expression of steroid hormone receptors, epidermal growth factor receptor, human epidermal growth factor receptor 2 (HER-2), and keratin 8. Global gene expression analysis by cDNA microarrays supported a correlation between the expression profiles of the primary tumor, lymph node metastasis, xenograft, and cell line. We conclude that L56Br-X1 and L56Br-C1 are useful model systems for studies of the pathogenesis and new therapeutic modalities of BRCA1-induced human breast cancer.     

Helicobacter pylori infection in Icelandic children

Objective: The prevalence of Helicobacter pylori (HP) infection is decreasing in the western world. The seroprevalence among 25–50-year-old Icelandic adults was recently shown to be 30–40%. Information on the seroprevalence in Nordic children is limited. We aimed at ascertaining the infection prevalence among healthy Icelandic children.

Methods: The infection status in stored frozen blood samples from two cross-sectional studies on the health of 7–9-year-old children (n?=?125) and 16–18-year-old adolescents (n?=?80) was determined by enzyme-linked immunosorbent assay (ELISA). Information on family demographics and GI symptoms was obtained by standardized questionnaires.

Results: Overall, 3.4% (7/205) of the children were infected with H. pylori. The prevalence was 2.6% (5/190), missing data n?=?3, among children with both parents born in a low prevalence country compared to 17% (2/12) among those with at least one parent born in a high prevalence area (p?=?.026). When at least one parent was born in a high prevalence country, the odds ratio for being H. pylori seropositive was 2.2 (95% CI, 1.02–54.67), when adjusted for the educational status of the mother. There was no significant association between H. pylori infection and gastrointestinal symptoms.

Conclusion: Prevalence of H. pylori infection in Iceland has become very low, suggesting a great reduction in transmission from older generations. There was an association between H. pylori infection and origin from high prevalence areas but not with gastrointestinal symptoms. The results mirror recent studies of children of Scandinavian ancestry.     

The effects of five-year growth hormone replacement therapy on muscle strength in elderly hypopituitary patients

OBJECTIVE: Little is known of the long-term effects of GH replacement therapy on muscle strength in elderly adults with adult onset GH deficiency (GHD). In this study, the effects of 5 years of GH replacement therapy on muscle function were determined in adults over 60 years of age with adult onset GHD. DESIGN: A prospective, open-label, single-centre study. Patients Twenty-six (12 male and 14 female) consecutive hypopituitary adults with adult onset GHD, mean age 65.0 (range 61-74) years. MEASUREMENTS: Upper leg muscle strength was measured using a Kin-Com dynamometer. Right and left handgrip strength were measured using an electronic grip force instrument. RESULTS: The mean insulin-like growth factor-I (IGF-I) SD score increased from -1.10 at baseline to 1.21 at end of the study. Body weight was unchanged during the 5-year study. A sustained increase in lean body mass and a sustained reduction of body fat was observed as measured using dual-energy X-ray absorptiometry (DEXA). The GH replacement therapy induced a sustained increase in isometric (60 degrees ) knee flexor strength. After statistical correction for age and sex variables using observed/predicted value ratios, a sustained increase was also observed in concentric knee flexor strength at an angular velocity of 60 degrees /s, concentric knee extensor strength at 60 degrees /s and 180 degrees /s, and peak right handgrip strength. At baseline, knee flexor strength was 90-96% of predicted, knee extensor strength was 85-87% of predicted, and hand-grip strength was 74-80% of predicted values. At study end, knee flexor strength was 98-106% of predicted, knee extensor strength was 90-100% of predicted, and hand-grip strength was 80-87% of predicted values. CONCLUSION: Elderly patients with adult onset GH deficiency had decreased baseline muscle strength also after correction for age and sex. The 5-year GH replacement therapy normalized knee flexor strength and improved, but did not fully normalize, knee extensor strength and handgrip strength.     

Body composition in young adult survivors of childhood acute lymphoblastic leukaemia

OBJECTIVE: Obesity is frequently reported in patients treated for childhood leukaemia. Obesity, particularly abdominal obesity, is one of the main characteristics of the metabolic syndrome and a risk factor for cardiovascular disease and non-insulin-dependent diabetes mellitus (NIDDM). DESIGN: All patients treated for acute lymphoblastic leukaemia (ALL) before the onset of puberty in the region of western Sweden, between 1973 and 1985, and in first remission, were included. 35 out of 47 patients aged 20-32 years participated. 19 patients had received cranial radiotherapy, and the median follow-up time was 20 years. The focus of this report was to study body composition and signs of the metabolic syndrome and correlate the findings to spontaneous growth hormone (GH) secretion. METHODS: Body composition was assessed using dual-energy X-ray absorbtiometry (DEXA). We analyzed serum concentrations of insulin, glucose, leptin and lipids. RESULTS: No patient was obese according to World Health Organization criteria (body mass index, BMI > or = 30 kg/m2) but one-third were overweight (BMI 25-29.9 kg/m2). The maximal GH peak during 24 h (GHmax) was correlated to percentage of total body fat (r = -0.42; P = 0.017), trunk fat (r = -0.5; P = 0.005) and fat-free mass (r = 0.42; P = 0.017). GHmax was also correlated to s-triglycerides (r = -0.54; P = 0.001), low-density lipoprotein-cholesterol (r = -0.382; P = 0.024) and high-density lipoprotein-cholesterol (r = 0.45; P = 0.007). CONCLUSIONS: We found little effect on BMI but an increased percentage of total body fat, especially trunk fat, and a tendency for an unfavourable lipid profile in adult survivors of childhood leukaemia. These findings were related to low endogenous GH secretion due to cranial irradiation.