Platelet-derived growth factor effects on purified testicular peritubular myoid cells: binding, cytosolic Ca++ increase, mytogenic activity, and extracellular matrix production enhancement

The response of purified rat testicular peritubular myoid cells (PMC) to platelet-derived growth factor (PDGF) was studied. Freshly isolated PMC were devoid of measurable amounts of PDGF-binding sites. However, after 1 day in culture in serum-free conditions, specific high affinity receptors were detected. The estimated binding sites per cell revealed that PMC express more receptors for PDGF-BB, followed by PDGF-AB and PDGF-AA. PDGF treatment of cultured PMC increased the cytosolic Ca2+ concentration, showing a rank order of potencies with PDGF-BB > PDGF-AB > PDGF-AA. PMC proliferation, as measured by direct cell counting, was also stimulated by all three PDGF isoforms, with the same order of potencies observed for the increase in intracellular Ca2+. This effect was inhibited by antibodies to PDGF. Moreover, PDGF treatment increased the release of type IV collagen and fibronectin, and induced the release of type V collagen and laminin. These results demonstrate that testicular PMC are induced to express functionally active PDGF receptors in response to cell culturing. These data suggest that PMC may be a target for PDGF and that PDGF-mediated effects in vivo are dependent on factors regulating the expression of the receptors. The role that PDGF may play in normal and pathological testicular processes is discussed

Transforming growth factor beta regulates differentiation and proliferation of human neuroblastoma

The effects of transforming growth factor-beta1 (TGFbeta) on two human neuroblastoma cell lines, LAN-5 and SK-N-AS, and one human glioblastoma cell line, GL15, were evaluated. Of the three cultures, only two, SK-N-AS and GL15, had a complete response to TGFbeta, with induction of the following effects: (i) inhibition of cell proliferation; (ii) up-regulation of the extracellular matrix glycoprotein fibronectin, together with down-regulation of the VLA5 integrin receptor; (iii) up-regulation of histotype-specific cytoskeletal intermediate filaments (neurofilaments for neuroblastoma and GFAP for glioblastoma); and (iv) increase in the glycoprotein CD44, only in SK-N-AS. In the third cell line, neuroblastoma LAN-5, the effects exerted by TGFbeta consisted only of (i) neurofilament increase and (ii) morphological differentiation. The TGFbeta receptor pattern was different in each culture: SK-N-AS expressed low rates of type I and type II receptors and high rates of type III receptor; LAN-5 expressed high rates of type I, low rates of type II, and no type III; GL15 expressed high rates of all three receptors. These data suggest that TGFbeta can induce a histotype-specific cell maturation and that the neuroblastoma expressing low type II and at the same time lacking type III receptor responds only partially to TGFbeta, with induction of neural differentiation but without inhibition of cell growth

Role of [18F]-FDG-PET/MDCT in evaluating early response in patients with Hodgkin's lymphoma.

PURPOSE: The authors evaluated the prognostic role of 18-fluoro-fluorodeoxyglucose positron emission tomography/multidetector computed tomography ([(18)F]-FDG PET/MDCT) in treating patients with Hodgkin's lymphoma (HL). MATERIALS AND METHODS: We retrospectively evaluated 132 patients with HL studied with PET/MDCT before the start of chemotherapy (CTX) for staging purposes and again after two CTX cycles with [doxorubicin (Adriblastin), bleomycin, vinblastine, dacarbazine (ABVD_] (interim PET/MDCT), at least 30 days after the end of the last CTX cycle and/or 3 months after the end of radiotherapy, if delivered (final PET-MDCT). RESULTS: Interim PET-MDCT was negative in 104/132 patients (79%), and their final PET-MDCT showed complete remission in 102/104 (98%) of cases, with disease recurrence/persistence in two (2%). In the remaining 28 (21%) patients, interim PET-MDCT revealed an early response in 68% of cases and chemoresistance with disease progression in 32% of cases; in these 28 patients, final PET-MDCT showed a lack of response to treatment in 43% of cases (43%) and complete remission in 57% of cases. Statistical analysis of these data showed that interim PET-MDCT had a negative predictive value of 98% and a positive predictive value of 42%, with values of sensitivity, specificity and diagnostic accuracy of 85.7%, 86.4% and 86.4%, respectively. CONCLUSIONS: Interim PET-MDCT has a reliable prognostic role in diagnosis and treatment of patients with HL, as it helps predict which patients are more likely to achieve a complete response at the end of treatment. PET/MDCT may also lead to a change in treatment, with reduced treatment-related toxic effects and significantly reduced total costs

Methicillin resistant- and Methicillin susceptible Staphylococcus aureus: comparison of genomic similarity of strains isolated from human and veterinary specimens using amplified fragment length polymorphism (AFLP).

In consequence of a previous study on Methicillin-resistant (MRSA) and Methicillin-susceptible (MSSA) Staphylococcus aureus isolated from veterinary samples, a correlated study was carried out to evaluate the genetic relatedness among MRSA and MSSA isolated from human and veterinary specimens using the amplified fragment length polymorphism (AFLP) fingerprinting technique. Twenty-four out of 32 veterinary strains and 21 out of 29 human strains were MRSA. The methicillin resistance was evaluated with E-test and the presence of mec A gene was confirmed with PCR. The results of the genomic analysis revealed that all the isolated strains were distinct. An analysis of molecular variance (AMOVA) was also carried out to verify the distribution of variance a) among and within strains of different origin (human and veterinary) and b) among and within MRSA and MSSA strains. The results showed that in both cases the major component of variance was within strains (76.66 and 92.55%, respectively, for the first and second case). A more accurate molecular technique, like AFLP rather PFGE, and the use of a sophisticate statistical analysis, like AMOVA, are strictly recommended to avoid that different strains are wrongly considered correlated

Is cerebral glucose metabolism affected by chemotherapy in patients with Hodgkin's lymphoma?

OBJECTIVE: The aim of the study was to investigate the effect of chemotherapy treatment with ABVD on brain glucose metabolism in patients with Hodgkin's disease (HD). METHODS: A total of 49 patients (23 men, 26 women; mean age 32±9 years) diagnosed with HD were included in the study. All of them underwent a baseline (PET0) and an interim (PET2) 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG) PET/computed tomography (CT) brain scan. All patients were treated after PET0 with two cycles of ABVD consisting of doxorubicin (adriamycin), bleomycin, vinblastine, and dacarbazine for 2 months. Thirty-five patients were evaluated further 15±6 days after four additional cycles (PET6). Differences in brain (18)F-FDG uptake were analyzed by statistical parametric mapping (SPM2). RESULTS: Compared with PET0, PET2 showed a significantly higher metabolic activity in the right angular gyrus (Brodmann area 39) and a significant metabolic reduction in Brodmann areas 10, 11, and 32 bilaterally. All these changes disappeared at PET6. CONCLUSION: Our results support the conclusion of a very limited impact of ABVD chemotherapy on brain metabolism in patients with HD