Localization and quantification of fluorescent inclusions embedded in a turbid medium

A set-up, based on a CCD camera, to localize fluorescent inclusions in diffusing media was developed. This set-up allows one to acquire a huge dataset along two axes. This aspect is fundamental to performing a tomographic reconstruction in order to quantify the fluorescence amplitude in each voxel of the sample. Firstly, a simple analytical approach to recover the position of a single inclusion, embedded in a turbid medium, was developed. Then, we implemented a reconstruction algorithm to recover the position of one and two inclusions and to estimate their relative concentrations. Finally, we studied the dependence of reconstructed data on the number of injection points of excitation light and the number of detection points of fluorescence emission.     

Human cortical responses during one-bit delayed-response tasks: an fMRI study

Neuroimaging study of cognition across aging requires simple tasks ensuring: (i) high rate of correct performances in neurophysiological settings; and (ii) significant modulation of cortical activity. As a preliminary step, the present functional magnetic resonance imaging (fMRI) study tested the hypothesis that very simple delayed-response tasks fit these requirements in normal young adults. The short-term memory (STM) variant included a sequence of cue stimulus (two vertical bars), delay period (blank screen for only 5s), go stimulus, and motor response compatible with the taller vertical bar. Noteworthy, the retention (only one bit) could be based on visuo-spatial, phonological, and somatomotor coding. In the control variant (no STM, NSTM), the cue stimulus was present during the delay period. Results showed high rate of correct performances in both tasks (about 95%). Compared to the NSTM task (delay period), the STM task enhanced cortical responses in bilateral dorsolateral prefrontal (Brodmann area 8-9 (BA 8-9)), lateral premotor (BA 6L), medial premotor (BA 6M), inferior parietal (BA 40), and superior parietal (BA 7) areas. In the STM task, cortical responses were stronger in right than left BA 8-9 and BA 6L. These results indicate that, in normal young adults, a simple STM variant of delayed-response tasks (one bit to be retained) is correctly performed and enhances bilateral fronto-parietal responses. Therefore, it may be used for future cognitive neuroimaging studies on aging.     

Functional topography of the secondary somatosensory cortex for nonpainful and painful stimulation of median and tibial nerve: an fMRI study

Functional magnetic resonance imaging (fMRI) was used to study the cortical activity of the bilateral secondary somatosensory cortex (SII) during nonpainful (motor threshold) and painful electrical stimulation of median and tibial nerves. fMRI recordings were performed in eight normal young adults. The aim was at evaluating the working hypothesis of a spatial segregation of nonpainful and painful populations not only in the "hand" representation of SII [Ferretti, A., Babiloni, C., Del Gratta, C., Caulo, M., Tartaro, A., Bonomo, L., Rossini, P.M., Romani, G.L., 2003. Functional topography of the secondary somatosensory cortex for nonpainful and painful stimuli: an fMRI study. NeuroImage 20, 1625-1638.] but also in its "foot" representation. Results showed that, in both "hand" and "foot" representations of bilateral SII, the activity elicited by the painful stimulation was localized more posteriorly with respect to that elicited by the nonpainful stimulation. A fine spatial analysis of the SII responses revealed a clear somatotopic organization in the bilateral SII subregion especially reactive to the nonpainful stimuli (i.e., segregation of the hand and foot representations). In contrast, it was not possible to disentangle the "hand" and "foot" representations of SII for painful stimuli. These results extended to the SII "foot" representation previous evidence of a spatial segregation in the SII "hand" representation of subregions for the painful and nonpainful stimuli. Furthermore, they suggest that noxious information is not somatotopically represented in human bilateral SII, at least as inferred from fMRI data at 1.5 T.     

Activation of the extracellular-signal regulated protein kinase pathway in human glomerulopathies

Examined was extracellular-signal regulated kinase (ERK) activation in normal human kidney (n = 2) and a cohort of glomerulopathies by immunohistochemistry staining for the dual-phosphorylated form of ERK (p-ERK). Cell proliferation was determined by expression of the proliferating cell nuclear antigen (PCNA). In normal human kidney, p-ERK was largely restricted to the cytoplasm of cells of the collecting duct (CD). In glomerulopathies, glomerular ERK activation was highly variable. However, there was colocalization of cell proliferation and ERK activation in the glomerular tuft and crescents. Tubular ERK activation in the different glomerulopathies was confined to the CD in areas with normal architecture. In contrast, ERK activation was prominent in tubules and interstitial cells in areas of tubulointerstitial damage. ERK activation was observed in glomerular and interstitial alpha-smooth muscle actin-positive myofibroblasts, but few macrophages or T cells showed ERK activation. There was a significant correlation between glomerular p-ERK+ and PCNA+ cells and between tubular p-ERK+ and PCNA+ cells. Glomerular p-ERK+ cells correlated with glomerular cellularity and the percentage of glomeruli with segmental lesions. Tubular p-ERK+ cells correlated with renal dysfunction and interstitial fibrosis and tubular atrophy. In conclusion, activation of the ERK pathway in human glomerulopathies correlates with cell proliferation, histologic lesions, and renal dysfunction. ERK activation may promote renal repair through tubular proliferation while promoting renal fibrosis via proliferation of glomerular and interstitial myofibroblasts.     

Effect of filgrastim on serum lactate dehydrogenase and alkaline phosphatase values in early breast cancer patients

To improve chemotherapy dose intensity and to optimize the use of granulocyte-colony stimulating factor, 506 patients with early breast cancer were randomly assigned to high dose epirubicin and cyclophospamide (EC) with or without prophylactic subcutaneously filgrastim, according to 5 different schedules: 480 µg or 300 µg daily or every other day, on day 8 through day 14, and 300 µg daily on days 8 and 12 of each chemotherapy course, Serum levels of lactate dehydrogenase (LDH) and alkaline phosphatase (AP) were significantly higher in patients given EC plus filgrastim than EC alone (P + 0.0001), the rate of G1-3 toxicity being 33.4% and 13.1% vs. 1.6% and 1%, respectively. No clinical evidence of filgrastim-related hepatic damage or significant difference in transaminase and γ-GT elevation was seen between the two groups. LDH and AP closely resembled peripheral blood leukocytes count and increased with increasing leucocytosis, throughout the 5 schedules. Although no patient continued treatment for filgrastim-related side effects, and LDH and AP rises resolved spontaneously within 3 weeks following the chemotherapy course, physicians should be aware of the transient and innocuous change in serum chemistry associated to leucocytosis, since it could be misinterpreted as expression of disease activity.     

Activation and cellular localization of the p38 and JNK MAPK pathways in rat crescentic glomerulonephritis

BACKGROUND: The p38 and c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) are intracellular signal transduction pathways involved in the production of inflammatory mediators. Little, however, is known about the contribution of these pathways to renal inflammation, nor the cell types in which these pathways are activated within normal and inflamed kidneys. The aim of this study was therefore to delineate the pattern and cellular localization of p38 and JNK activation in normal rat kidney and rat acute and chronic inflammatory renal disease. METHODS: Normal male Sprague-Dawley rats and groups of rats given accelerated anti-glomerular basement membrane (GBM) disease were killed at 3 hours, day 1, day 7, or day 28 and examined for p38 and JNK pathway activation by Western blotting and immunolocalization of the phosphorylated p38 (p-p38) and JNK (p-JNK) kinases. RESULTS: In terms of glomerular MAPK activation, Western blotting identified the presence of both p-p38 and p-JNK in normal glomeruli, localized by immunohistochemistry to podocytes and epithelial cells of Bowman's capsule. In anti-GBM disease, Western blotting showed that p38 activation peaked at 3 hours and remained elevated above normal throughout the disease time course. JNK activation (via the 54 kD isoform) likewise increased at 3 hours of anti-GBM disease and remained elevated throughout disease. At 3 hours, p-p38, but not p-JNK, was localized to neutrophils and glomerular endothelial cells. p-JNK was localized to glomerular endothelial cells at day 7. Macrophages, lymphocytes, activated podocytes, and myofibroblasts were positive for both p-p38 and p-JNK. In terms of tubular MAPK activation, Western blotting identified p38 and JNK activation in tubules of normal kidney. Immunostaining showed that most cortical tubules contained some p-p38 and p-JNK stained cells. There was a significant increase in tubular p38 activation at 3 hours of anti-GBM disease, followed by increased JNK activation of the 54 kD isoform from day 7 onward, and the 46 kD isoform at day 28. Immunostaining of diseased tissue localized p-p38 and p-JNK to virtually all cortical tubular cells. CONCLUSION: The p38 and JNK MAPK pathways are activated in glomeruli and tubules of normal kidney. In acute anti-GBM disease, there was an increase in p38 activation within glomerular endothelial cells and within infiltrating neutrophils, suggesting an important role for p38 MAPK in acute inflammation. In progressive anti-GBM disease, p38 and JNK activation in podocytes, glomerular endothelial cells, infiltrating macrophages, T cells, and myofibroblasts suggests that both the p38 and JNK MAPK pathways are important in chronic inflammation and fibrosis. Blockade of these pathways may therefore be potentially therapeutic in the treatment of acute and chronic renal inflammation.     

Complete surgical resection of a huge thoracic mass consisting in a localized fibrous tumor simulating a high-grade malignant neoplasm

Solitary fibrous tumour is an infrequent neoplasm generally arising from the parietal and visceral pleura. The diagnosis may be difficult in the presence of a history of malignant disease owing to the different presentations and to radiological findings of evident invasiveness. The authors report the case of a woman with a right giant fibrous solitary tumour of the pleura twenty years after a subcutaneous mastectomy with axillary dissection and radiation therapy for breast cancer. The biopsy diagnosis was consistent with a probable solitary fibrous tumour of the pleura but the discrepancy with the radiological images and the difficult differential diagnosis versus a malignant sarcoma, possibly radio-induced, prompted us to verify the real features of the disease. The patient was submitted to a right anterolateral thoracotomy and partial sternotomy and the giant mass was resected enbloc with the phrenic nerve and diaphragm which proved to be the only structures tightly adhering to the neoplasm. Histological examination confirmed the diagnosis of a solitary fibrous tumour of the pleura. The patient is still alive and disease-free 30 months after the surgical operation. Fibrous solitary tumour is a disease generally characterised by a good prognosis but in particular cases, with unmistakable radiological findings of invasiveness, a precise diagnosis must be obtained in order to choose the most appropriate therapy.     

Breast cancer metastatic to the choroid in a male patient: case report

Choroidal metastases have been observed in about 8% of patients with metastatic breast cancer, even if their true incidence is likely to be higher, as they are not routinely investigated in the absence of symptoms. Radiotherapy is the treatment of choice for symptom palliation. The prognosis is traditionally poor, with a reported average survival of one year. Here we describe the third case reported in the literature of a metastatic tumor to the choroid from a male breast carcinoma.