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Biomedical subjects

D Lombardi

Publications and source records attributed to D Lombardi.

At least 55 records · Page 3Linked to original sources
PubMed1996

Cavernous haemangioma of the pineal region.

Cavernous haemangiomas rarely occur in the pineal region, only eight histologically verified cases have been reported to date. Clinically and radiographically, they are often confused with other tumours of the pineal region, particularly germ cell tumours. When radiotherapy is performed without the benefit of biopsy, cavernous haemangiomas as well as other radioresistant neoplasms may be unnecessarily treated. We report two surgically treated cases of cavernous haemangioma of the pineal region, and comment upon one treated by shunt placement alone. Two cases were associated with an adjacent venous malformation. In all instances, magnetic resonance imaging (MRI) permitted a correct pre-operative diagnosis. We conclude that surgical exploration and total resection is the treatment of choice when the diagnosis of cavernous haemangioma is suspected on the basis of neuro-imaging. A conservative attitude is justifiable in the case of elderly patients with a higher surgical risk.

Adult↗
PubMed1996

nm23 influences proliferation and differentiation of PC12 cells in response to nerve growth factor.

The nm23 genes codify nucleoside diphosphate kinases, which have been shown to be involved in the regulation of microtubule dynamics. We have demonstrated previously that the association between the Nm23-M1 protein and cytoskeletal beta-tubulin correlates with cell differentiation. It is known that microtubules and microtubule-associated proteins are fundamental elements regulating neuronal differentiation. In the present study, we have investigated the ability of nm23 to influence nerve growth factor-induced PC12 cell differentiation. To this end, we have altered PC12 intracellular levels of nm23-M1 by means of sense and antisense transfections. In the presence of nerve growth factor, overexpression of nm23 delays cell cycle transition, rapidly induces neurite outgrowth, and increases the expression of neurofilament and microtubule proteins. On the contrary, down-regulation of nm23 enhances cell proliferation and inhibits neuronal differentiation. These findings indicate that neuronal cell proliferation and differentiation can be modulated by nm23 expression levels.

Animals↗
PubMed1995

The association of the Nm23-M1 protein and beta-tubulin correlates with cell differentiation.

The Nm23 protein is a nucleoside diphosphate kinase (NDPK) and is thought to play a critical role in metastatic behavior. It has been reported that a NDPK activity is present in microtubules assembled in vitro. Since microtubule assembly is determinant in cell growth and differentiation, we investigated whether Nm23-M1 forms molecular complexes with beta-tubulin in murine cells either actively proliferating or differentiating. For this purpose a polyclonal antibody against the GST-Nm23-M1 fusion protein was generated and employed to detect Nm23-M1/beta-tubulin complexes in murine tumor cells derived from the Lewis lung carcinoma (3LL) and in undifferentiated and differentiated myogenic cells (C2C12). Immunoblotting and immunoprecipitation experiments performed using the anti-fusion protein antibody demonstrated that the Nm23-M1 protein is detectable in in vitro tumor cell lines and in in vivo primary tumors but not in spontaneous lung metastases. These data are in good agreement with data previously reported. Immunoprecipitation experiments demonstrated that the Nm23-M1 protein forms complexes with beta-tubulin in in vitro tumor cell lines, but not in primary tumors. Furthermore, the Nm23-M1 protein forms complexes with beta-tubulin in myogenic cells prior to and after differentiation. Interestingly, however, the level of the Nm23-M1/beta-tubulin complexes is remarkably increased in differentiated myotubes. In conclusion, the results indicate that the Nm23-M1 protein forms molecular complexes with beta-tubulin and that the number of complexes increases during the differentiation process of murine cells.

Animals↗
PubMed1995

Modulation of experimental mesangial proliferative nephritis by interferon-gamma.

The observation that interferon-gamma (IFN-gamma) inhibits cell proliferation and collagen synthesis of a variety of cell types in culture has suggested that IFN-gamma may be useful in the treatment of fibroproliferative diseases. We administered recombinant IFN-gamma subcutaneously (10(5) U/kg/day for 3 days) to rats, beginning one day after the induction of mesangial proliferative nephritis with anti-Thy 1 antibody. IFN-gamma reduced glomerular (primarily mesangial) cell proliferation by 44% at days 2 and 4 compared to vehicle injected control rats with anti-Thy 1 nephritis (that is, proliferating cells that excluded the macrophage marker, ED-1, P < 0.001). Despite the inhibition of mesangial cell proliferation, IFN-gamma did not reduce the overall extracellular matrix deposition (by silver stain) or deposition of type IV collagen or laminin (by immunostaining) at 4 or 7 days, and glomerular type IV collagen and laminin mRNA levels were increased (1.4 and 1.7-fold) at 4 days relative to controls. The inability of IFN-gamma treatment to reduce mesangial matrix expansion may relate to the fact that IFN-gamma treated rats had a twofold increase in glomerular macrophages (that is, ED-1 positive cells, P < 0.001 at 2 and 4 days) with an increase in oxidant producing cells (day 2, P < 0.05) and a 1.6-fold increase in glomerular TGF-beta mRNA expression (4 days). This suggests that the effect of IFN-gamma to inhibit mesangial cell proliferation in glomerulonephritis may be offset by the ability of IFN-gamma to increase glomerular macrophages and TGF-beta expression. These data also show that IFN-gamma can partly dissociate the mesangial proliferative response from the extracellular matrix expansion in glomerulonephritis.

Animals↗
PubMed1994

Sellar and parasellar extra-axial cavernous hemangiomas.

Cavernous hemangiomas can grow extra-axially within dural sinuses, particularly the cavernous sinus and present like tumours. Five cases of cavernous hemangiomas arising within or from the wall of the cavernous sinus are reported. Three of them had an "endophytic" growth within the cavernous sinus with a lateral extension into the middle cranial fossa, a medial extension into the sella and an anterior extension into the superior orbital fissure. Two cases presented with an "exophytic" extension from the sinus wall at the point of entry of the third and fourth cranial nerves respectively. These patterns of growths are best appreciated by MRI. Keeping in mind that these lesions are contained within a pseudocapsule will help in planing surgical strategy. Characteristic MRI findings of cavernous hemangiomas in this location include hypo-intensity on T 1-weighted images, marked hyperintensity on T2-weighted images and Gadolinium enhancement.

Adult↗
PubMed1994

Osteopontin expression in angiotensin II-induced tubulointerstitial nephritis.

Osteopontin is an arginine-glycine-aspartate (RGD) containing secreted phosphoprotein recently shown to stimulate a local macrophage influx when injected subcutaneously in mice. We examined the effect of angiotensin II infusion on renal injury and osteopontin expression in the rat kidney by in situ hybridization and immunohistochemistry. Preceding pathologic changes in tubular and interstitial cells, a dramatic increase in renal osteopontin protein and mRNA levels was observed primarily in epithelial cells of the distal tubules, collecting ducts and Bowman's capsule. Although both cortex and medulla showed increased osteopontin levels, the effect was most pronounced in the renal cortex which normally showed very little constitutive osteopontin expression. Interestingly, regions of the kidney expressing high osteopontin levels correlated with sites of monocyte/macrophage accumulation. These observations, coupled with recent findings that osteopontin may be a pro-inflammatory protein, suggests that osteopontin over-expression may facilitate monocyte/macrophage accumulation at the sites of renal tubulointerstitial injury.

Angiotensin II↗
PubMed1994

Prophylaxis of complications after pancreatic surgery: results of a multicenter trial in Italy. Italian Study Group.

An Italian prospective multicentre study evaluated the efficacy of octreotide, a synthetic somatostatin analogue, in preventing the complications of elective pancreatic surgery. 303 patients with tumours of the pancreas or the ampullary region, in whom ultrasonography and computed tomography scan had shown a resectable lesion, or with chronic pancreatitis, were randomized in a double-blind fashion to treatment with octreotide 100 micrograms t.i.d. s.c. starting at least 1 h before surgery and continued till the 7th postsurgical day, or with matching placebo. Unresectable lesions were found at laparatomy in 31 patients (15% of those with tumours). In 14 others, procedures not anticipated in the study protocol had to be performed, and in 6 additional cases there were other protocol violations so that these 20 patients were excluded from the study analysis. Considering the 252 evaluable patients, the complication rate was significantly higher in the 130 placebo-treated patients than in the 122 who received octreotide (29.2 vs. 15.6%; p = 0.01). We therefore suggest that octreotide may substantially reduce the risk of complications after elective pancreatic surgery.

Chronic Disease↗
PubMed1994

Mesangial cell apoptosis: the major mechanism for resolution of glomerular hypercellularity in experimental mesangial proliferative nephritis.

Increases in mesangial cell number may herald glomerular scarring, but they are not irreversible. This study sought mechanisms by which surplus glomerular mesangial cells can be cleared. A small proportion of cultured mesangial cells exhibited typical morphological features of apoptosis (programmed cell death), which was increased by growth factor deprivation or exposure to cycloheximide, stimuli known to increase apoptosis in other cell types. Apoptosis was confirmed by typical internucleosomal chromatin cleavage. In vivo, clear morphological evidence of mesangial apoptosis leading to phagocytosis by neighboring mesangial cells was obtained in self-limited mesangial proliferation induced in rats by Thy1.1 antibody, apoptosis occurring approximately 10-fold more frequently than in the healthy rat glomerulus. Indeed, changes in glomerular cell number in Thy1.1 nephritis strongly suggested that apoptosis is the major cell clearance mechanism counterbalancing cell division, thereby mediating resolution of glomerular hypercellularity in experimental mesangial proliferation.

Animals↗
PubMed1994

[The use of polypropylene (Marlex) mesh in ambulatory care of inguinal hernia].

The use of Marlex mesh in the treatment of inguinal hernia produces a series of advantages, if compared with traditional techniques. According to the authors, these advantages can be identified with the ambulatorial treatment of this pathology, with the possibility to use the local anaesthetic, with a minimum postoperating pain, with a possible collaboration of the patients with the surgeon during the operation, and with a considerable reduction of relapses. The authors explain the different steps of their techniques.

Adolescent↗
PubMed1994

Tubulointerstitial disease in glomerulonephritis. Potential role of osteopontin (uropontin).

Interstitial inflammation and tubular injury accompany most types of glomerulonephritis and are likely to mediate progressive renal injury. We hypothesized that the interstitial monocyte/macrophage accumulation in nephritis involves osteopontin, a cell attachment glycoprotein that avidly binds macrophages in vitro and induces a macrophage-rich infiltrate on subcutaneous injection in mice (Singh et al, J Exp Med, 1990, 171: 1931). In this study, we demonstrate that osteopontin messenger RNA and protein levels are up-regulated in a proportion of proximal and distal tubules in three experimental models of glomerulonephritis. In all three models, the expression of osteopontin initially precedes histological evidence of tubular injury, but is correlated with subsequent sites of monocyte/macrophage accumulation and tubular damage. Osteopontin expression also correlates with the severity of the tubulointerstitial injury, being greatest in amino-nucleoside nephrosis. These data suggest that 1) osteopontin is up-regulated in tubules in glomerular disease; 2) osteopontin may be important for macrophage accumulation at specific sites in diseased tissue; and 3) osteopontin may therefore have a role in the pathogenesis of the tubulointerstitial injury that accompanies glomerulonephritis.

Animals↗
PubMed1993

A 13 kb resolution cosmid map of the 14 Mb fission yeast genome by nonrandom sequence-tagged site mapping.

We present the application of a nonrandom sequence-tagged site (STS) content detection method in mapping an entire genome, that of fission yeast. The novelty of our strategy is in the use of STS probes made from both ends of cosmid clones, selected on the basis of "sample without replacement" (only library clones that show no previous positive hybridization are selected and made into probes). We developed powerful techniques, based on consistency analysis, for error detection and contig assembly. In addition, we probed our library with genetically mapped markers and Notl or Sfil linking clones, thereby anchoring contigs onto chromosomes. Our map contains more than 1000 sites, including genes (most were previously unmapped), occurrences of known repetitive elements, and Notl-Sfil restriction sites.

Chromosome Mapping↗
PubMed1993

Rab9 functions in transport between late endosomes and the trans Golgi network.

Rab proteins represent a large family of ras-like GTPases that regulate distinct vesicular transport events at the level of membrane targeting and/or fusion. We report here the primary sequence, subcellular localization and functional activity of a new member of the rab protein family, rab9. The majority of rab9 appears to be located on the surface of late endosomes. Rab9, purified from Escherichia coli strains expressing this protein, could be prenylated in vitro in the presence of cytosolic proteins and geranylgeranyl diphosphate. In vitro-prenylated rab9 protein, but not C-terminally truncated rab9, stimulated the transport of mannose 6-phosphate receptors from late endosomes to the trans Golgi network in a cell-free system that reconstitutes this transport step. Rab7, a related rab protein that is also localized to late endosomes, was inactive in the in vitro transport assay, despite its efficient prenylation and capacity to bind and hydrolyze GTP. These results strongly suggest that rab9 functions in the transport of mannose 6-phosphate receptors between late endosomes and the trans Golgi network. Moreover, our results confirm the observation that a given organelle may bear multiple rab proteins with different biological functions.

Amino Acid Sequence↗
PubMed1992

Effect of high-dose methylprednisolone on anti-oxidant enzymes after experimental SAH.

Lipid peroxidation has been considered one of the most important factors involved in the pathogenesis of neuronal damage following subarachnoid hemorrhage. In the brain, the protective systems most involved against peroxidative and free radicals generated reactions are superoxide-dismutase (SOD) and glutathione-peroxidase (GSH-Px). Since these activities are subjected to a significant reduction following experimental SAH induction in rats, we investigated in the present study if the beneficial effect of high-dose methylprednisolone (MP) in inhibiting lipid peroxidative processes in SAH is possibly linked to an influence on anti-oxidant enzymatic activities. In brain cortex, after MP treatment, Cu-Zn SOD activity in the early phase and more dramatically in the late phase after SAH was restored (4.06 +/- 0.06 and 4.07 +/- 0.14 enzymatic units/mg of protein, respectively) if compared to hemorrhagic non-treated controls (3.69 +/- 0.16 and 2.96 +/- 0.06 enzymatic U/mg of protein) while Mn-SOD and GSH-Px activities were improved in treated animals only in the early and late phases after SAH, respectively. In the hippocampus, in treated rats Cu-Zn activity was partially restored only at 6 h, while Mn-SOD activity recovered at 48 h after SAH; no significant changes in GSH-Px activity were found in treated animals at any time. In the brain stem, in treated animals, Cu-Zn SOD activity was restored in the early phase (3.86 +/- 0.12 enzymatic U/mg of protein) up to control values of non-hemorrhagic rats (3.44 +/- 0.30 enzymatic U/mg of protein), while GSH-Px activity recovered in the late phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Renal injury from angiotensin II-mediated hypertension.

Angiotensin II (Ang II)-mediated hypertension induces vascular smooth muscle cell hypertrophy and hyperplasia in systemic blood vessels, but the effects of Ang II on the intrinsic cell populations within the kidney have been less well characterized. We infused Ang II for 14 days into rats by minipump at doses (200 ng/min) that resulted in moderate hypertension (mean systolic blood pressure 156-172 mm Hg). Small renal arterial vessels of Ang II-infused rats demonstrated focal injury with fibrinoid necrosis and medial hyperplasia, whereas the glomerular capillaries demonstrated only rare segmental hyalinosis. Proliferation of vascular smooth muscle cells was pronounced (fourfold to 20-fold increase in [3H]thymidine incorporation) as opposed to a minimal proliferation of glomerular cells in Ang II-infused rats. In contrast, the principal effect of Ang II in glomeruli was to increase the expression of alpha-smooth muscle actin by mesangial cells and desmin by visceral glomerular epithelial cells. Ang II-infused rats also developed focal tubulointerstitial injury, with tubular atrophy and dilation, cast formation, an interstitial monocytic infiltrate, and mild interstitial fibrosis with increased type IV collagen deposition. The injury was associated with a proliferation of distal tubule, collecting duct, and interstitial cells as determined by immunostaining for proliferating cell nuclear antigen, and was accompanied by an increase in platelet-derived growth factor B-chain messenger RNA in the area of interstitial injury as localized by in situ hybridization. Renal interstitial cells also underwent phenotypic modulation in which they expressed alpha-smooth muscle actin. Vehicle-infused control rats displayed no tubular injury, proliferation, or phenotypic modulation. Thus, Ang II in doses that cause moderate hypertension induces marked vascular, glomerular, and tubulointerstitial injury with cell proliferation, leukocyte recruitment, phenotypic modulation with the upregulation of proteins normally associated with smooth muscle cells, and interstitial fibrosis.

Angiotensin II↗