Surface markers of primate B and T lymphoid cell lines identified by antibodies to human and simian lymphocyte antigens

Simian B and T lymphoid cell lines were shown to maintain surface markers found on mature lymphocytes in vivo. The T lymphoid cell lines expressed Ia-like antigens on their surfaces, further suggesting that they represent mature, activated T cells. These Ia antigens show a structural similarity to Ia on human cells although some diversity exists. The Ia antigen expressed on T lymphoid cell lines was shown to be very similar to those on B lymphoid cell lines. Owl monkey and marmoset T lymphoid cell lines were also shown to express a VH immunoglobulin-related determinant, a marker which is thought to be associated with T cell antigen receptor. Owl monkey and marmoset T cell lines express a surface antigen which identifies the sheep erythrocyte receptor on human T cells and some of these lines express an antigen found on human helper T cells. It is noteworthy that substantial conservation of surface components has occurred within primate evolution such that monoclonal antibodies to human Ia, OKT-11a and Leu 3a markers can be used to type lymphocytes of lower primates.     

Interactive effects of pertussis toxin and the phorbol ester tumour promotor, phorbol dibutyrate, on T-lymphocyte mitogenesis and the expression of phenotypic determinants.

The B oligomer of pertussis toxin serves as a weak mitogen in the T lymphocyte, an effect which is associated with an early rise in cytosolic free calcium concentrations, as monitored by Fura-2 fluorescence. Upon co-administration of phorbol dibutyrate, a phorbol ester tumour promotor which activates protein kinase C, pertussis toxin-induced proliferation was synergistically enhanced, as measured by the increased uptake of [3H]thymidine, into cellular DNA. Although phorbol ester co-administration has often been associated with an inhibition of Ca2+-mobilizing pathways, phorbol dibutyrate pretreatment had no inhibitory effect on the pertussis toxin-induced calcium flux and may actually have enhanced this response slightly. Flow cytometric analysis of cell populations expanded by the combined regimen did not provide evidence for the preferential expansion of cells bearing either CD4 or CD8, the T-cell determinants representative of the helper-inducer and cytotoxic-suppressor subsets, respectively. Pertussis toxin and phorbol dibutyrate appear, therefore, to elicit polyclonal stimulation, rather than the selective activation of a given lymphocyte subset. Expression of the transferrin receptor, a marker for nutrient uptake, and CD25, the Tac component of the interleukin-2 (IL-2) receptor, was, however, synergistically enhanced in cells activated by the co-treatment procedure.     

Osteopenia in anorexia nervosa: specific mechanisms of bone loss.

Osteopenia is a well recognized medical complication of anorexia nervosa (AN). The mechanism of bone loss is not fully understood and there is uncertainty about its management. New markers of bone turnover have been developed. C-terminal type 1 propeptide (PICP) is a measure of bone formation and urinary pyridinolines such as deoxypyridinoline (DPYRX) and serum carboxyterminal crosslinked telopeptide (ICTP) are markers of bone resorption. The aim of this study was to examine these bone markers in patients with AN. Twenty female patients with AN and 12 healthy controls were included in the study. Bone mineral density (BMD) of AN patients was measured by dual energy X-ray absorptiometry (DEXA). Lumbar bone density was significantly reduced in the AN group compared to standardised values of thirty year old adults (t-score 83.2%, S.D. 12.1). Femoral neck bone density showed an even greater reduction (t-score 79.4%, S.D. 13.5). We found a significant negative correlation between femoral BMD and the duration of the illness. Femoral BMD correlated significantly with minimal body weight (r(16) = 0.504, p = 0.033). The markers of bone resorption were significantly higher in the patients with AN compared to the values of the control group (ICTP t(30) = -2.15, p = 0.04, DPYRX t(25) = -2.26, p = 0.033), whereas the markers of bone formation did not differ significantly between the groups. AN appears to be a low turn over state associated with increased bone resorption without concomitant bone formation. This pattern differs from osteopenia in menopausal women and should, therefore, lead to the development of specific therapeutic strategies in AN associated osteopenia. Hormone replacement therapy as well as calcium and vitamine D-supplementation are so far discussed controversially. Long-term treatment studies are warranted.     

Accelerated partial breast irradiation with external beam radiotherapy

Background and purpose

To evaluate the feasibility and efficacy of external beam three-dimensional (3D) conformal accelerated partial breast irradiation (APBI) for selected patients with early breast cancer.

Patients and methods

Between 2011 and 2016, 72 patients were recruited for this prospective phase 2 trial. Patients were eligible for APBI if they had histologically confirmed breast cancer or pure ductal carcinoma in situ (DCIS), a tumor diameter ≤3 cm, clear resection margins ≥2 mm, no axillary lymph node involvement, no distant metastases, tumor bed clips, and were aged ≥50 years. Patients were excluded if mammography showed a multicentric invasive growth pattern, or if they had residual diffuse microcalcifications postoperatively, an extensive intraductal component, or vessel invasion. Patients received 3D conformal external beam APBI with a total dose of 38 Gy in 10 fractions in 1–2 weeks. The trial had been registered at the German Clinical Trials Register, DRKS-ID: DRKS00004417.

Results

Median follow-up was 25.5 months (range 1–61 months). Local control was maintained in 71 of 72 patients. The 3?year local recurrence rate was 2.1% (95% confidence interval, CI: 0–6.1%). Early toxicity (grade 1 radiodermatitis) was seen in 34.7% (25/72). Late side effects ≥ grade 3 did not occur. Cosmetic results were rated as excellent/good in 96.7% (59/61).

Conclusion

APBI with external beam radiotherapy techniques is feasible with low toxicity and, according to the results of the present and other studies, on the way to becoming a standard treatment option for a selected subgroup of patients.

     

Synthesis and biological activity of 22-deoxo-23-oxa analogues of saponin OSW-1

Analogues of the potent cytotoxic saponin OSW-1 were prepared from the readily available steroidal 16β,17α,22-triol. The new 22-deoxo-23-oxa analogues of OSW-1 were screened against eight cancer cell lines and normal human fibroblasts. The analogues proved to be slightly less active than OSW-1 but also less toxic to normal cells. They induce concentration- and time-dependent apoptosis of mammalian cancer cells with caspase-3 activation.