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Biomedical subjects

D Lombardi

Publications and source records attributed to D Lombardi.

At least 73 records · Page 4Linked to original sources
PubMed1992

Phenotypic and functional modifications of thymocytes during tumor growth.

Thymocytes (T) from mice bearing the syngeneic tumor 3LL inhibit the immune response to SRBC by syngeneic splenocytes derived from control mice and cultured in Mishell and Dutton's antibody forming systems. T from control mice are devoid of this capacity but acquire it after in vitro incubation with tumor cells. It has been shown that metabolites of arachidonic acid (PGE-2, LTB-4 and LTC-4) synthesized in excess by tumor cells act as mediators for the acquisition of the above capacity by thymic cells in vitro. Surface phenotypical analysis by flow-cytometry demonstrated that in the thymus of tumor bearing mice the proportion of both single positive thymocytes (L3T4+/LY2- and L3T4-/LY2+) and of double negative thymocytes (L3T4-/LY2-) increased with a parallel decrease in the proportion of double positive cells (L3T4+/LY2+). In the mean time the total number of thymocytes markedly decreased. An attempt was done to mimic in vitro what happens in vivo. For this purpose T from control mice were incubated with conditioned culture medium in which 3LL cells had grown or with arachidonic acid metabolites. After one or the other of these treatments T from control mice did not modify their phenotypic antigenic pattern but acquired the capacity to negatively interfere with the in vitro immune response of normal spleen cells to SRBC. Since serum from tumor bearing mice contains large amounts of PGE-2, LTB-4 and LTC-4 we tested its effects on normal syngeneic T. Serum from tumor bearing mice, but not serum from normal mice, induces T from control syngeneic animals to acquire both immunosuppressive capacity and differentiation pattern clusters similar to those that characterize T derived from the thymus of tumor bearing mice. We demonstrated that metabolites of arachidonic acid are active as inducers of immunosuppressive capacity in T. On the other hand, a yet unknown factor present in serum of tumor bearing mice plays a role as inducer of differentiation of these cells.

Animals↗
PubMed1991

Role of alpha beta receptor heterodimer formation in beta platelet-derived growth factor (PDGF) receptor activation by PDGF-AB.

We investigated the ability of highly purified recombinant platelet-derived growth factor (PDGF) AB to interact with the products of alpha and beta receptor genes expressed in cells independently or concurrently. Although PDGF-AB lacked any detectable ability to bind or activate beta receptors in cells expressing only this receptor, efficient beta receptor activation by this ligand was readily observed in cells coexpressing alpha platelet-derived growth factor receptors (alpha PDGFRs). beta receptor activation induced by PDGF-AB was shown to be dependent upon in vivo physical association of this receptor with alpha PDGFRs. Moreover, cross-linking analysis established the existence of PDGF-AB-induced beta PDGFR dimers in vivo. All of these findings argue that initial PDGF-AB interaction with the alpha PDGFR induces conformational changes in the ligand or receptor that facilitates efficient recruitment of beta PDGFR by this PDGF isoform.

Animals↗
PubMed1991

[Circumscribed peritonitis of colonic origin].

The Authors present their personal experience of circumscribed peritonitis of colic origin. They review some physiopathological aspects of these peritonitis and then emphasize the new therapeutic possibilities offered by percutaneous prick echo or TC guided.

Colonic Diseases↗
PubMed1991

Molecular cloning and characterization of 2B7, a rat mRNA which distinguishes smooth muscle cell phenotypes in vitro and is identical to osteopontin (secreted phosphoprotein I, 2aR).

We have identified a rat smooth muscle cell mRNA, 2B7, which distinguishes smooth muscle cell phenotypes in vitro. Sequence and tissue distribution data strongly suggest this mRNA to be identical to osteopontin (secreted phosphoprotein I, 2aR). In vivo, 2B7 mRNA is expressed in normal rat aorta and carotid arteries at levels 50-60-fold greater than heart, and about 3-4 times the levels found in adult rat kidney on a per micrograms of total RNA basis. Of the other smooth muscle sources surveyed, significant levels of 2B7 mRNA were detectable in total RNA prepared from rat uterus and stomach, but not intestine. 2B7 mRNA levels in both carotid and aortic artery increase with age, and are elevated approximately 5-fold in the carotid artery 48 h after balloon angioplasty. The presence of osteopontin (secreted phosphoprotein I, 2aR) in the normal artery wall and its increased expression after injury suggests a previously unappreciated role for this molecule in the vascular system.

Amino Acid Sequence↗
PubMed1991

"Ex vivo" release of eicosanoid from human brain tissue: its relevance in the development of brain edema.

The specific mechanism underlying the genesis of vasogenic brain edema is still debated: the role of arachidonic acid is considered extremely important, as it is a possible activator of self-maintaining reactions enhancing the release of vasoactive and cytotoxic compounds. The relationship between arachidonic acid metabolism and brain edema has been studied primarily in brain tissue samples or in the extracellular fluid, whereas the residual capacity of perilesional tissue to synthesize and release eicosanoids has not been investigated. In the present study, perilesional samples of brain tissue were available from 4 patients operated on for brain metastasis, from 8 patients who had malignant neuroepithelial tumors, from 4 with meningiomas, and from 5 with subarachnoid hemorrhage. A brain edema index was calculated from the preoperative computed tomographic scan. The "ex vivo" method allowed determination of the residual capacity of endogenous arachidonic acid metabolism. The edema index is significantly higher in patients with brain metastasis (6.5 +/- 0.8) and neuroepithelial tumors (3.6 +/- 0.2) than in those with meningiomas (1.5 +/- 0.06), subarachnoid hemorrhage (1.7 +/- 0.18), and in controls. In patients with metastatic and neuroepithelial tumors there is a significant correlation between peritumoral brain edema and the capacity to synthesize leukotriene C4 (P less than 0.05); the capacity to synthesize leukotriene C4 is also significantly elevated after subarachnoid hemorrhage (13.91 +/- 2.6 ng/ml of incubation medium) when compared with control cases (5.56 +/- 0.91). The capacity to synthesize prostacyclin is significantly higher in patients with brain metastasis than in those with neuroepithelial tumors and meningiomas (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Deletion or substitution within the alpha platelet-derived growth factor receptor kinase insert domain: effects on functional coupling with intracellular signaling pathways.

The tyrosine kinase domains of the platelet-derived growth factor (PDGF) and colony-stimulating factor-1 (CSF-1)/c-fms receptors are interrupted by kinase inserts (ki) which vary in length and amino acid sequence. To define the role of the ki in the human alpha PDGF receptor (alpha PDGFR), we generated deletion mutants, designated alpha R delta ki-1 and alpha R delta ki-2, which lacked 80 (710 to 789) and 95 (695 to 789) amino acids of the 104-amino-acid ki region, respectively. Their functional characteristics were compared with those of the wild-type alpha PDGFR following introduction into a naive hematopoietic cell line, 32D. Biochemical responses, including PDGF-stimulated PDGFR tyrosine phosphorylation, phosphatidylinositol (PI) turnover, and receptor-associated PI-3 kinase activity, were differentially impaired by the deletions. Despite a lack of any detectable receptor-associated PI-3 kinase activity, 32D cells expressing alpha R delta ki-1 showed only partially impaired chemotactic and mitogenic responses and were capable of sustained proliferation in vitro and in vivo under conditions of autocrine stimulation by the c-sis product. 32D transfectants expressing the larger ki deletion (alpha R delta ki-2) showed markedly decreased or abolished biochemical and biological responses. However, insertion of the highly unrelated smaller c-fms (685 to 750) ki domain into alpha R delta ki-2 restored each of these activities to wild-type alpha PDGFR levels. Since the CSF-1R does not normally induce PI turnover, the ability of the c-fms ki domain to reconstitute PI turnover in the alpha R delta ki-2 transfectant provides evidence that the ki domain of the alpha PDGFR does not directly couple with this pathway. Taken together, all od these bindings imply that their ki domains have evolved to play very similar roles in the known signaling functions PDGF and CSF-1 receptors.

Animals↗
PubMed1991

Tyrosine mutations within the alpha platelet-derived growth factor receptor kinase insert domain abrogate receptor-associated phosphatidylinositol-3 kinase activity without affecting mitogenic or chemotactic signal transduction.

A phosphatidylinositol-3 (PI-3) kinase activity of unknown biological function associates with tyrosine kinase-containing proteins, including a number of growth factor receptors after ligand stimulation. In the beta platelet-derived growth factor (beta PDGF) receptor, phosphorylation of a specific tyrosine residue within the kinase insert domain was required for its interaction with this enzyme. We show that substitutions of phenylalanine for tyrosine residue 731 or 742 within the kinase insert domain of the alpha PDGF receptor do not impair PDGF-induced tyrosine phosphorylation of the receptor or of an in vivo substrate, phospholipase C-gamma. Moreover, phosphatidylinositol turnover in response to ligand stimulation is unaffected. However, both lesions markedly impair receptor association with PI-3 kinase. Antiphosphotyrosine antibody-recoverable PI-3 kinase was also dramatically reduced in PDGF-stimulated cells expressing either mutant receptor. Since neither mutation abolished PDGF-induced mitogenesis or chemotaxis, we conclude that alpha PDGF receptor-associated PI-3 kinase activity is not required for either of these major PDGF signalling functions.

Amino Acid Sequence↗
PubMed1991

Effect of high-dose methylprednisolone and U74006F on eicosanoid synthesis after subarachnoid hemorrhage in rats.

Free radicals and lipid peroxidation of membrane fatty acids are thought to play a role in the pathogenesis of arterial vasospasm and the physiopathologic patterns of neuronal damage after subarachnoid hemorrhage. We have evaluated the effects of treatment with either high-dose methylprednisolone every 8 hours or a single dose of U74006F on the temporal profile of ex vivo synthesis of four selected eicosanoids in brain slices after experimental induction of subarachnoid hemorrhage in rats. Prostaglandins D2 and E2, prostacyclin and leukotriene C4 levels were determined by radioimmunoassay after 1-hour incubation of the brain slices. The synthesis of prostaglandin D2 and 6-ketoprostaglandin F1 alpha at 48 hours after subarachnoid hemorrhage was significantly higher when compared to sham-operated animals (p = 0.01); prostaglandin E2 release was significantly enhanced at 6 hours after subarachnoid hemorrhage (p = 0.01). The release of the lipoxygenase metabolite was significantly enhanced at 1, 6, and 48 hours after subarachnoid hemorrhage induction. Both treatment regimens significantly reduced the ex vivo synthesis of prostaglandin D2, prostaglandin E2, and leukotriene C4 at 1, 6, and 48 hours after subarachnoid hemorrhage, whereas the effects on 6-ketoprostaglandin F1 alpha synthesis differed in the two treatment groups. U74006F enhanced the synthesis of prostacyclin metabolite in the early phase after subarachnoid hemorrhage, and high-dose methylprednisolone reduced the increasing synthesis at 48 hours. A strict comparison between the two treatments was not possible because of the different modalities of administration. However, these data suggest that the antioxidant effect of single-dose treatment with U74006F influenced the early and delayed effects on enzymatic lipid peroxidation, whereas the effects of methylprednisolone administration every 8 hours were more significant in the delayed phase.

Animals↗
PubMed1991

Symptomatic subependymoma: a clinicopathological and flow cytometric study.

Twenty-one intracranial subependymomas were reviewed with regard to presentation, diagnosis, operative findings, and long-term follow-up data. The histopathological features were critically reviewed, and deoxyribunucleic acid analysis was performed by flow cytometry. The patients' mean age was 48.5 years (range 32 to 72 years). In 14 cases the tumor was located in the fourth ventricle, in six within a lateral ventricle, and in one in the third ventricle with extension into the lateral ventricle. Radiographic characteristics included isodensity with minimal enhancement on computerized tomography, frequent dystrophic calcification, and isointensity on T1-weighted or slight hyperintensity on T2-weighted magnetic resonance images. The predominant histological features in all cases were those of classic subependymoma. Nonetheless, pathological examination showed a minor (less than 20%) ependymoma component in five cases, significant cytological atypia in seven, mitoses in 11, endothelial prominence in four, and focal hemorrhage-associated necrosis in two. Flow cytometry revealed a diploid pattern in 12 patients, tetraploidy in two, and aneuploidy in one. Two patients died in the perioperative period. Of the remaining 19, 12 underwent gross total resection (two of whom received postoperative irradiation) and seven underwent subtotal resection (five of whom received irradiation). None of the 12 non-irradiated patients developed tumor progression or died of direct tumor-related causes. Of the seven irradiated patients, follow-up imaging studies demonstrated their tumors to be radioresponsive, particularly with doses of 5000 cGy or greater. Despite the presence of cytological atypia and mitotic activity in the majority of cases, the prognostic effects of such factors as tumor location and the extent of surgical resection outweighed those of the standard histopathological parameters. Routine postoperative irradiation is not recommended, but should be reserved for cases with a symptomatic residual or recurrent subependymomas following surgery.

Adult↗
PubMed1991

"Angioglioma" and the arteriovenous malformation-glioma association.

The term "angioglioma" denotes a highly vascular glioma, most of which are low-grade lesions associated with a favorable prognosis. The authors encountered an example of this pathology, a cystic oligodendroglioma associated with prominent vasculature which both clinically and histologically mimicked an occult arteriovenous malformation (AVM). This case and reports of the association of AVM and glioma prompted a histological review of 1034 surgically resected AVM's, both angiographically occult and visible, among which no oligodendroglial or astrocytic forms of "angioglioma" were found. Eight cases were observed, however, wherein oligodendroglial cells were increased in number within or about the malformation. Two basic histological patterns of oligodendroglial cell excess were seen; one appeared to be malformative in nature with abnormal disposition of oligodendroglial cells being an integral part of the AVM, whereas in the other an apparent increase in cellularity seemed the result of chronic ischemia with condensation of white matter. It appeared that the areas of increased oligodendrocyte content seen in association with AVM are non-neoplastic lesions that exhibit two rather distinct histological patterns of differing origin. In an effort to determine the frequency of "angioglioma," the authors examined Tissue Registry data for several glioma groups in which highly vascular examples are prone to occur. Tumors selected for study included 104 cerebellar-type (pilocytic) astrocytomas, 82 oligodendrogliomas, and 51 supratentorial pilocytic astrocytomas. Histological hypervascularity mimicking a vascular malformation (that is, an "angioglioma") was encountered in 5%, 4%, and 12% of the cases, respectively. Based upon clinical, radiological, and pathological reviews of these cases, as well as a careful review of the literature, it was concluded that 1) "angiogliomas" are neither rare nor represent a distinct clinicopathological entity; 2) in histological but not necessarily angiographic surgical terms, they represent simply highly vascular gliomas, usually of low grade; and 3) the clinicopathological and angiographic features as well as the prognosis of such lesions do not differ from those of similar gliomas without angioma-like vasculature. Finally, "angiogliomas" must not be confused with gliomas of high-grade malignancy which, due to neovascularity, may be highly vascular at angiography and at surgery.

Adolescent↗
PubMed1991

The new pyramid: laying the groundwork with motivational power.

To successfully implement a comprehensive, progressive management system, a manager must incorporate daily administrative or executive principles and duties with an array of motivational tactics. Various motivational strategies have been discussed since the generation of industrial psychological research, which is generally conceded to have had its genesis with Abraham Maslow. Maslow's simple premise regarding man's needs for self-esteem, security and affiliation is at the root of many theories and practicums in vogue today.

Career Mobility↗
PubMed1991

[Acute pseudoabdomen. A proposed nosographic picture].

The authors put forward a new and original classification of the clinical pictures of acute pseudo-abdomen. They separate the cases due to extra-abdominal causes which are not marked by the essential features of acuity and severity from those which do not require surgery.

Abdomen, Acute↗
PubMed1990

[Indications and surgical tactics in ulcerative rectocolitis. Our experience].

Surgical indications in URC are examined in relation to various situations of election, emergency and urgency. The various possible surgical procedures are analysed, stress being laid on criteria of choice which take account of the seriousness of the disease and of the different technical solutions now available. A series of 30 operations in 145 cases of URC is presented and complications examined in relation to the type of operation performed and to the indications. Stress is laid on the importance of intervening adequately so as to achieve the best prognostic results.

Adolescent↗
PubMed1990

Experimental isobaric subarachnoid hemorrhage: regional mitochondrial function during the acute and late phase.

Patients treated for aneurysmal subarachnoid hemorrhage show, in the long-term follow up, an elevated rate of cognitive disturbances that are mainly related to the impact of the initial bleeding: the neurotoxic effects of blood deposition in subarachnoidal spaces may result in a diffuse encephalopathy, but the intrinsic mechanism and the biochemical correlates are not known. In the present study we have evaluated mitochondrial function after experimental induction of subarachnoid hemorrhage. Mitochondrial function was evaluated in four different rat brain areas (frontal cortex, occipital cortex, hippocampus, and brain stem) after experimental isobaric subarachnoid hemorrhage in rats. Subarachnoid hemorrhage was induced by injecting 0.07 mL of arterial autologous blood into the cisterna magna. Intracranial pressure did not significantly increase. The nonsynaptic mitochondrial fraction was isolated from different rat brain areas, and the maximal rate of enzymatic reactions of some key enzymatic activities related to the Krebs cycle [nicotinamide adenine dinucleotide (oxidized form) (NAD+)-isocitrate dehydrogenase, citrate synthase, and succinate dehydrogenase] and of the electron transfer chain (cytochrome oxidase) were evaluated. The nonsynaptic mitochondrial fraction was utilized also to check parameters related to the mitochondrial respiration: state 3, state 4, uncoupled state, respiratory control ratio, and adenosine 5'-diphosphate/oxygen ratio. The biochemical parameters were measured at 1 and 72 hours after the subarachnoidal injection of blood. Subarachnoid hemorrhage did not affect the mitochondrial enzymatic activities both at 1 and 72 hours, while the mitochondrial enzymatic activities parameters were significantly affected: in particular, a significant decrease of respiratory control ratio in all tested brain areas was demonstrated. The increased mitochondrial vulnerability in the delayed phases could be one of the biochemical correlates of post-hemorrhagic encephalopathy.

Analysis of Variance↗
PubMed1990

Macrophage-colony-stimulating factor (CSF-1) induces proliferation, chemotaxis, and reversible monocytic differentiation in myeloid progenitor cells transfected with the human c-fms/CSF-1 receptor cDNA.

The c-fms protooncogene encodes the receptor for macrophage-colony-stimulating factor (CSF-1). Expression vectors containing either normal or oncogenic point-mutated human c-fms genes were transfected into interleukin 3 (IL-3)-dependent 32D cells in order to determine the effects of CSF-1 signaling in this murine clonal myeloid progenitor cell line. CSF-1 was shown to trigger proliferation in association with monocytic differentiation of the 32D-c-fms cells. Monocytic differentiation was reversible upon removal of CSF-1, implying that CSF-1 was required for maintenance of the monocyte phenotype but was not sufficient to induce an irrevocable commitment to differentiation. Human CSF-1 was also shown to be a potent chemoattractant for 32D-c-fms cells, suggesting that CSF-1 may serve to recruit monocytes from the circulation to tissue sites of inflammation or injury. Although c-fms did not release 32D cells from factor dependence, point-mutated c-fms[S301,F969] (Leu-301----Ser, Tyr-969----Phe) was able to abrogate their IL-3 requirement and induce tumorigenicity. IL-3-independent 32D-c-fms[S301,F969] cells also displayed a mature monocyte phenotype, implying that differentiation did not interfere with progression of these cells to the malignant state. All of these findings demonstrate that a single growth factor receptor can specifically couple with multiple intracellular signaling pathways and play a critical role in modulating cell proliferation, differentiation, and migration.

Animals↗
PubMed1990

High-dose methylprednisolone and 'ex vivo' release of eicosanoids after experimental subarachnoid haemorrhage.

In the present study we have investigated the effects of high-dose methylprednisolone (MP) treatment on the 'ex vivo' release of four major eicosanoids in an experimental model of subarachnoid haemorrhage (SAH) with the aim of verifying: (a) the efficacy in reducing arachidonic acid metabolism enhancement; (b) whether high-dose methylprednisolone is effective on both the cyclooxygenase and lipoxygenase pathways; and (c) discussing the possible role of high-dose MP treatment in brain protection after SAH. Levels of prostaglandin D2 and E2, prostacyclin and also leukotriene C4 were determined by the radioimmunoassay technique after 1 h incubation of cerebral cortex samples of rats which had been subjected to experimental SAH procedure (injection of 0.3 ml of autologous arterial blood). The release of prostaglandin D2 at 48 h after SAH is significantly higher when compared to that of sham-operated animals (P less than 0.01); prostaglandin E2 release is significantly enhanced at 6 h after the SAH procedure (P less than 0.01); release of the lipoxygenase metabolite is significantly enhanced at 1, 6 and 48 h after SAH induction; MP significantly decreases the release of all eicosanoids, and values in treated animals do not differ from those of sham-operated animals. The results of the present study suggest that the global inhibitory effect of high-dose MP treatment on the 'ex vivo' release of eicosanoids after experimental SAH could be considered to be one of the neurochemical correlates for the reduced incidence and severity of arterial inflammatory response, which results in chronic vasospasm and supports the clinical evidence of MP efficacy in preventing or reducing the incidence of arterial vasospasm after aneurysmal rupture.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Extra-axial cavernous hemangiomas involving the dural sinuses.

Extra-axial cavernous hemangiomas are rare lesions previously associated with unacceptable mortality and morbidity rates that precluded surgical resection. The authors analyze the clinical presentation, surgical results, and histology of eight intrasinus cavernous hemangiomas: six located in the cavernous sinus, one in the petrosal sinus, and one in the torcula. Magnetic resonance imaging is the best radiographic test for surgical planning. Successful tumor removal was achieved in six cases with no mortality and low morbidity. In the remaining two patients, only subtotal resection was achieved because of massive hemorrhage in one and the misdiagnosis of a pituitary adenoma leading to a transsphenoidal approach in the other. For hemangiomas arising within the cavernous sinus, extradural removal of the sphenoid bone facilitated preservation of the neurovascular structures. Since the clinical and histological characteristics of these lesions are distinct from intra-axial cavernous hemangiomas, a more appropriate term may be "sinus cavernoma" to indicate that these lesions are primarily intrasinus in origin.

Adult↗