Summary:Keywords: AML; inv(16); CBF␤/MYH11; MRD; BMTWe evaluated the occurrence of the CBF␤/MYH11 fusion transcripts by PCR analysis in 10 patients with Acute myelomonocytic leukemia with bone marrow eosinoinv(16)(p13;q22) acute myeloid leukemia (AML) who philia (AML-M4Eo), according to the French-Americanunderwent allogeneic bone marrow transplantation British (FAB) classification, is a distinct subtype of AML. (BMT) (n = 5), peripheral blood progenitor cell trans-AML-M4Eo is often associated with rearrangements of plantation (PBPCT) (n = 3), or autologous transplanchromosome 16, mostly involving 16p13 and 16q22, leadtation (n = 2). In addition to the analysis of minimal ing either to a pericentric inversion, inv(16)(p13q22) or, residual disease (MRD), the chimerism status of patients less commonly, to a translocation between the homologous after allogeneic transplant was studied by PCR. The chromosomes, t(16;16)(p13;q22). The pericentric inversion CBF␤/MYH11 fusion trancript was not detectable in six inv(16)(p13q22) is one of the most frequently occurring of seven patients who remained in remission after allochromosomal rearrangements detected in this neoplasm, geneic BMT or PBPCT. Two of these patients in which has been reported to account for approximately 16% remission were monitored for 50 months and 64 months of all AML. undergo allogeneic BMT have a significantly lower risk of transcript was detectable. In one patient in relapse, the relapse than their counterparts treated with chemotherapy fusion transcript was not only detectable in blood and alone. On the other hand allogeneic BMT is associated with bone marrow, but also in a cerebrospinal fluid sample more treatment-related mortality than autologous BMT or prior to transplant. Two patients who received autologchemotherapy alone. ous BMT were monitored for CBF␤/MYH11 transcripts Several reports suggest that the CBF␤/MYH11 fusion 3 months after BMT. The CBF␤/MYH11 was detected mRNA can often be detected in patients in long-term in these patients. Both patients subsequently relapsed 3 remission after chemotherapy. [4][5][6][7] To date, other than single months and 23 months post-autologous BMT. The case reports, studies of the detection of the CBF␤/MYH11 results study show that analysis of the CBF␤/MYH11 fusion transcripts after allogeneic BMT do not exist. institution. In addition to the analysis of minimal residual Germany

Breast cancer metastasizes to bone more frequently than to any other organ, and over 80% of advanced breast cancer patients develop bone metastases. Our recent demonstration that human breast cancer cells express bone sialoprotein (BSP), a bone matrix protein, provides a possible clue for the selective affinity of breast cancer cells for bone. We tested the hypothesis that detection of BSP in primary human breast cancer could be a potential indicator of the ability of breast cancer cells to metastasize to bone. BSP expression was evaluated in the primary breast cancers of 39 patients using immunoperoxidase and two specific anti-BSP antibodies. None of these patients presented clinically or scintigraphically detectable bone metastases at the time of surgery. In the course of their disease, 22 patients developed clinically diagnosed bone metastases. Expression of BSP in breast cancer cells from patients who developed bone metastases was significantly higher (p = 0.008, according to the Mann-Whitney test) than in patients with no bone involvement. No association was found between BSP expression in the primary breast lesions and axillary lymph node metastases. BSP expression was significantly increased in infiltrating ductal carcinoma compared with infiltrating lobular carcinoma (p = 0.0023). No correlation was found between immunoreactivity to BSP antibodies and estrogen receptor (ER) status, progesterone receptor (PR) status, or age. Our data suggest that BSP could help to identity which women will develop bone metastases and provide new bases for the understanding of the molecular mechanism(s) responsible for breast cancer cells osteotropism.

Abstract— The influx and efflux of [3H]GABA were investigated in synaptosomes. Two efflux components were detected. The first, termed spontaneous efflux, was not affected by the external sodium chloride concentration. The second, termed GABA‐stimulated efflux, was observed when low levels of GABA were added to the incubation medium and was found to require external sodium chloride. The rate of spontaneous efflux at 0°C was about 37 per cent of the rate at 27°C but both GABA‐stimulated efflux and GABA influx were completely inhibited at 0°C. The stimulation of efflux by external GABA followed simple Michaelis–Menten kinetics with respect to external GABA. The concentration of external GABA required for half‐maximal stimulation was 4·9 ± 1·4 μm and the Vmax for efflux was 1·0 ± 0·6 nmol. min‐1.mg‐1 of protein. A similar stimulation of efflux was observed with GABA analogue l‐2,4‐diamino‐butyric acid which is a competitive inhibitor of influx. The concentration of external l‐2,4‐diaminobutyric acid required for half‐maximal stimulation of efflux was 51 ± 12 μm and the Vmax for efflux was 0·8 ± 0·5 nmol.min‐1.mg‐1 of protein. Since the sodium‐dependency, temperature sensitivity, and kinetic properties of the GABA‐stimulated efflux system were similar to the influx system, GABA‐stimulated efflux was attributed to carrier‐mediated exchange diffusion. Measurement of efflux and influx in the same preparation showed there was a net efflux when total fluxes were considered and that the exchange ratio (influx to GABA‐stimulated efflux) was 0·9 when carrier‐mediated fluxes were considered. The effect of the temperature of the fluid used to rinse synaptosomes collected on filters in influx experiments was investigated. There was no detectable difference in measured values of influx between samples rinsed with cold fluid (0°C) and warm fluid (27°C). The endogenous GABA content of synaptosomes was found to be 20·3 ± 2·5 nmol GABA per mg of protein. From this value, the cytoplasmic concentration of GABA in synaptosomes was estimated to be a maximum of 40 mm. About 5 per cent of total cerebral cortical GABA was found in the synaptosomal fraction.

Osteoporosis is associated with an increased rate and older age with a decreased rate of HRT prescription, whereas no difference is observed in association with cardiovascular or breast cancer risk.