TGF-beta1 increases tyrosine hydroxylase expression by a mechanism blocked by BMP-2 in human neuroblastoma SH-SY5Y cells

Human neuroblastoma SH-SY5Y cells were used to study the effects of transforming growth factor beta1 (TGF-beta1) and bone morphogenetic protein 2 (BMP-2) on neuronal differentiation and acquisition of a catecholaminergic phenotype. SH-SY5Y cells express the intracellular factors activated through the receptors of the TGFbeta superfamily members, Smad1 and Smad4, as in basal conditions or after differentiation with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or retinoic acid (RA). TGF-beta1 and BMP-2 induce differentiation in SH-SY5Y cells by different pathways: the effect of TGF-beta1 is potentiated by TPA and the effect of BMP-2 is blocked by RA. Cell differentiation due to TGF-beta1 treatment is accompanied by an increase in tyrosine hydroxylase (TH) expression, more pronounced in the presence of TPA or RA and counteracted by BMP-2. BMP-2 and RA both induce noncatecholaminergic cell differentiation, and together they may induce choline acetyltransferase expression in serum-cultured cells. In conclusion, our results suggest that TGF-beta1 and BMP-2 may contribute, in opposite ways, to regulation of the neuronal catecholaminergic phenotype.     

Interpretative reading of the non-fermenting gram-negative bacilli antibiogram

Among non-fermenting Gram-negative rods, the most clinically important species are Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia, which are frequently multiresistant. P. aeruginosa resistance to beta-lactams depends on the production of chromosomal and plasmid-mediated beta-lactamases, altered permeability (loss of OprD porin is related to carbapenem-resistance) and active efflux pumps, particularly MexAB-OprM. In aminoglycoside-resistant strains the main mechanism of resistance is the production of inactivating enzymes; the efflux pump MexXY-OprM is also involved. Quinolone-resistance in P. aeruginosa is related to changes in topoisomerases, altered permeability and efflux pumps. The mechanisms of resistance of A. baumannii have not been well characterized, which makes interpretative reading of the antibiogram in this organism difficult. Resistance to beta-lactams is associated with the production of beta-lactamases and altered penicillin-binding proteins. Resistance to aminoglycosides has been related to modifying enzymes and resistance to quinolones to altered targets. S. maltophilia is resistant to carbapenems and other beta-lactams because of the production of two beta-lactamases (L-1 and L-2). Aminoglycoside-modifying enzymes have also been described in this species. In contrast to what is observed in other organisms, S. maltophilia resistance to quinolones has been mainly related to active efflux, rather than to target alterations.     

Activation of pyramidal cells in rat medial prefrontal cortex projecting to ventral tegmental area by a 5-HT1A receptor agonist.

5-HT(1A) receptor agonists increase the activity of dopamine (DA) neurons in the ventral tegmental area (VTA) and DA release in medial prefrontal cortex (mPFC). The mPFC is enriched in 5-HT(1A) receptors and projects to the VTA, where mesocortical dopaminergic neurons originate. We examined whether 5-HT(1A) receptor activation can modulate the activity of mPFC pyramidal neurons projecting to VTA. These were identified by antidromic stimulation from the VTA and were recorded extracellularly in anesthetized rats. The selective 5-HT(1A) agonist BAY x 3,702 (10-80 microg/kg i.v.) increased the firing rate in 14/19 neurons (283 +/- 79%) and reduced the activity of 5/19 neurons (22 +/- 11%), resulting in an overall 2.2-fold increase of the firing rate. Both effects were blocked by the selective 5-HT(1A) antagonist WAY-100635. These results suggest that the increase in dopaminergic activity produced by 5-HT(1A) receptor activation can be driven by an increase in the activity of projection neurons in mPFC.     

Importance of radiotherapy in the outcome of patients with primary CNS lymphoma: an analysis of the CHOD/BVAM regimen followed by two different radiotherapy treatments.

PURPOSE: To assess the effect of a reduced dose of radiotherapy (RT) in patients with primary CNS lymphoma (PCNSL) responding to the cyclophosphamide, doxorubicin, vincristine, and dexamethasone (CHOD)/carmustine, vincristine, methotrexate, and cytarabine (BVAM) regimen. PATIENTS AND METHODS: Patients received one cycle of CHOD and two of BVAM. In the first trial, all 31 patients received 45-Gy whole-brain RT (CHOD/BVAM I). In the second, with 26 patients, RT dose was reduced to 30.6 Gy if there was a complete response (CR) after chemotherapy (CHOD/BVAM II). RESULTS: Age, performance status, and chemotherapy received were similar in both protocols. CR rate at the end of all treatment was 68% for CHOD/BVAM I and 77% and for CHOD/BVAM II. Treatment modality was the only predictor of relapse, with 3-year relapse risks of 29% and 70% for CHOD/BVAM I and II, respectively. This was specifically important in the 25 patients less than 60 years old (3-year relapse risk, 25% v 83%; P =.01). The 5-year overall survival (OS) was 36%. Age (< 60 v > or = 60 years) was the only predictor for OS in the multivariate analysis (relative risk, 2.1; 95% confidence interval, 1.4 to 2.8). RT dose was the only predictor of OS in patients younger than 60 years old who achieved CR at the end of all treatment (3-year OS, 92% v 60% for patients receiving 45 or 30.6 Gy, respectively; P =.04). CONCLUSION: Reduction of the RT dose from 45 Gy to 30.6 Gy in patients younger than 60 years old with PCNSL who achieved CR resulted in an increased risk of relapse and lower OS.     

A comparative study of HER2/neu amplification and overexpression using fluorescencein situ hybridization (FISH) and immunohistochemistry (IHC) in 101 breast cancer patients

The HER2/neu protooncogene is expressed in the breast, ovarian, gastric and prostatic tumors. Studies done in a number of laboratories have demostrated that 25%–30% of breast cancer contain overexpression of HER2/neu gene. A comparative analysis of the amplification and overexpression of HER2/neu using fluorescencein situ hybridization (FISH) and immunohistochemistry (IHC) was performed to determine the correlation between both techniques. In this study, FISH with HER2/neu probe (Path Vysion) is compared to immunohistochemistry (rabbit anti-human c-erbB-2-DAKO) in a series of 101 prospective human breast cancer specimens. Among 25 patients with score of IHC 3+, 23 (92%) were detected amplified by FISH and in two cases we found overexpression (3+) but without gene amplification. Out of 46 cases with 2+ by IHC, we found 43 not amplified, two moderately amplified (<10 copies) and one highly amplified (>10 copies) (6.5%). No patient with IHC O or 1+, presented amplification of HER2/neu. A good correlation between both techniques was found. FISH technique should have clinical utillity overoat in cases with 2+.     

Impact of hematological diagnosis on early and late outcome after laparoscopic splenectomyrid=""

Background: Laparoscopic splenectomy (LS) is now regarded as the treatment of choice for autoimmune thrombopenia (ITP). However, there have been few reports describing the application of LS to other splenic diseases, such as malignant entities and conditions associated with splenomegaly. Hematological diseases have specific clinical features that can influence immediate outcome after LS. Although the long-term effects of LS are unknown, a risk of splenosis has been suggested. Therefore, we designed a study to analyze the impact of primary hematological disease on immediate and late outcome in a prospective series of LS patients. Methods: We performed a prospective analysis of 111 LS done between February 1993 and March 1999. The patients were classified by hematological indications into the following four groups: (a) group 1, low platelet count. This group was further subdivided into group 1A, idiopathic thrombocytopenic purpura (ITP) (n= 48) and group 1B, HIV-related ITP (n= 8); (b) group 2, anemia. This group was further subdivided into group 2A, autoimmune hemolytic anemia (n= 8), and group 2B, spherocytosis (n= 11); (c) group 3, malignancy (n= 28); and (d) group 4, others (n= 8). Immediate outcomes were recorded prospectively. Hematological status and late complications were reviewed after a mean follow-up of 24 ± 18 months. Results: There were no significant differences between the groups in terms of conversion, transfusion requirements, and morbidity, although transfusion and morbidity were slightly higher in group 3. However, hospital stay was significantly longer in groups 3 and 4 than in groups 1 and 2. Long-term follow-up showed satisfactory hematological results in ≥75% of patients (group 1A, 82%; group 1B, 88%; group 2A, 88%; group 2B, 100%; group 3, 75%; group 4, 88%). Overall, late morbidity was 8.3% and mortality was 6.2%, mainly due to deaths in group 4 (six of 22 patients). Conclusion: LS is a safe and reproducible procedure for most hematological indications, with a similar immediate outcome for benign diseases and a long-term hematological response comparable to the standard results that have been observed in open series. Received: 1 April 1999/Accepted: 22 November 1999/Online publication: 8 May 2000     

The influence of age on early surgical treatment of acute cholecystitis

This study was undertaken to assess the influence of age on the early surgical treatment of acute cholecystitis. One hundred consecutive patients who had early operations for acute cholecystitis were divided into two groups according to age. Group 1 consisted of 41 patients who were younger than 60 years of age, and group 2 was made up of 59 patients who were more than 60 years of age. Shock, leukocytosis, hyperglycemia and uremia were more common in those patients in group 2 (p less than 0.05). The over-all diagnostic effectiveness was 94 per cent. The mortality rate was 4.1 per cent (n = 4). There were no significant differences in morbidity and mortality between both groups. In conclusion, advanced age is not a contraindication for early surgical treatment of acute cholecystitis.     

Solid-pseudopapillary tumor of pancreas

Solid-pseudopapillary tumor of pancreas is a very rare neoplasm of low malignant potential and unknown origin. It generally occurs in young women and the prognosis is usually good after complete surgical removal. Two cases of solid pseudopapillary tumor with distinct disease duration are reported.