Wild type p73 overexpression and high-grade malignancy in breast cancer

The overexpression of wild type p73 is the most frequent alteration of p73 in malignancies. We investigated, in 70 breast carcinomas, p73 mRNA expression and its relationship to p53 mutations, determined by an immunohistochemical method, and loss heterozygosity (LOH) status of the 1p36 region, together with its possible implication in the pathogenesis of breast carcinomas. LOH, amplifying DNA by PCR using 5 markers, of 1p36 region (one intragenic to p73 gene) was found in 17% of cases but no significant correlation was observed with p73 overexpression. p53 positive immunostaining was present in 33% of breast carcinomas, and these exhibited a statistically significant relation with p73 overexpressed tumors. Overexpression of p73 mRNA was observed in 19 tumors (27%). The analysis of cases with p73 overexpression and cases with normal mRNA expression, in terms of age and pathologic characteristics of the tumors showed a significant association of p73 overexpression and tumors with lymph node metastases, vascular invasion and higher pathologic stage. These results suggest that p73 overexpression is a molecular alteration that could be implicated in the tumorigenesis of breast carcinomas and, eventually, in a poor clinical behavior.     

Gasless laparoscopic cholecystectomy is not moretime-consuming

apd: 4 September 2001     

Basiliximab induction improves the outcome of renal transplants in children and adolescents

Thirty-two children and adolescents received their renal transplant at the Montefiore Medical Center, in New York, between October 1996 and May 2000. Twenty-four patients received basiliximab, in addition to tacrolimus and steroids (basiliximab group). The remaining eight patients received only tacrolimus and steroids (non-basiliximab group). The 1-year patient survival rate was 100% in both groups. The 1-year graft survival rate was 87.5% for the basiliximab group and 75% for the non-basiliximab group (P=0.45). The rates of acute rejection in the basiliximab and non-basiliximab groups were 26% and 43%, respectively (P=0.36). However, in recipients with ≤3 HLA mismatches, the rate of acute rejection was zero in the basiliximab group, and 40% in the non-basiliximab group (P=0.04). The beneficial effect occurred despite the fact that tacrolimus was maintained at below the target levels. There were no adverse events directly attributable to the administration of basiliximab. There were no cases of opportunistic infections or post-transplant lymphoproliferative disease. In summary, addition of basiliximab to tacrolimus and prednisone significantly decreased the rate of acute rejection in well-matched patients. Moreover, this effect was manifest at lower, and therefore less toxic, tacrolimus levels. Received: 19 December 2000 / Revised: 23 April 2001 / Accepted: 24 April 2001     

Development of in vivo ventilatory and single chemosensitive neuron responses to hypercapnia in rats

We used pressure plethysmography to study breathing patterns of neonatal and adult rats acutely exposed to elevated levels of CO2. Ventilation (VE) increased progressively with increasing inspired CO2. The rise in VE was associated with an increase in tidal volume, but not respiratory rate. In all animals studied, the CO2 sensitivity (determined from the slope of the VE vs. inspired % CO2 curve) was variable on a day to day basis. Chemosensitivity was high in neonates 1 day after birth (P1) and fell throughout the first week to a minimum at about P8. Chemosensitivity rose again to somewhat higher values in P10 through adult rats. The developmental pattern of these in vivo ventilatory responses was different than individual locus coeruleus (LC) neuron responses to increased CO2. The membrane potential (V(m)) of LC neurons was measured using perforated patch (amphotericin B) techniques in brain slices. At all ages studied, LC neurons increased their firing rate by approximately 44% in response to hypercapnic acidosis (10% CO2, pH 7.0). Thus the in vivo ventilatory response to hypercapnia was not correlated with the V(m) response of individual LC neurons to hypercapnic acidosis in neonatal rats. These data suggest that CO2 sensitivity of ventilation in rats may exist in two forms, a high-sensitivity neonatal (or fetal) form and a lower-sensitivity adult form, with a critical window of very low sensitivity during the period of transition between the two (approximately P8).