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Biomedical subjects

P Gallo

Publications and source records attributed to P Gallo.

At least 19 recordsLinked to original sources

Production of hemolymphopoietic cytokines (IL-6, IL-8, colony-stimulating factors) by normal human astrocytes in response to IL-1 beta and tumor necrosis factor-alpha.

Astrocyte-enriched populations were established from human embryonic brain analyzed for their ability to synthesize cytokines potentially relevant for mechanisms of inflammation and immunity in the brain. Unstimulated astrocytes did not secrete significant IL-6, IL-8, macrophage CSF (M-CSF), granulocyte-macrophage CSF (GM-CSF), or granulocyte-CSF (G-CSF), as determined by specific ELISA and/or bioassay. With the exception of M-CSF mRNA, transcripts for the above factors were not detected in unstimulated astrocytes. On exposure of human astrocytes to IL-1 beta, high levels of IL-6, IL-8, M-CSF, G-CSF, and GM-CSF mRNAs were detected; moreover, active secretion of all the above cytokines was demonstrated. TNF-alpha was also able to stimulate IL-6, IL-8, M-CSF, GM-CSF, and G-CSF synthesis and secretion, but was generally less potent than IL-1 beta. No IL-3 mRNA or protein was detected in unstimulated or cytokine-treated astrocytes. IL-1 alpha and IL-1 beta mRNAs and proteins were not detected in unstimulated astrocytes, but were present in very small amounts after stimulation with TNF-alpha/IL-1 beta. No IL-6, M-CSF, GM-CSF, G-CSF, or IL-8 were induced by IL-1 beta or TNF-alpha in early primary cultures, which mainly contain undifferentiated neuronal/glial progenitor cells. These studies demonstrate for the first time the production of multiple cytokines by normal human astrocytes stimulated in culture by IL-1 beta and TNF-alpha. The capacity of human astrocytes to synthesize and release cytokines active on hemolymphopoietic cells supports the concept that these cells play an important role in the regulation of inflammatory and immune responses in a variety of brain pathologies.

Astrocytes

Muscarinic cholinergic receptors in the human right coronary artery: a receptor binding and autoradiographic study.

We used a combination of radioreceptor binding and autoradiographic techniques to study the pharmacological characteristics and anatomical localization of [3H]-quinuclidinyl benzilate (QNB) binding sites in the human right coronary artery. The ligand was bound to sections of the human right coronary artery in a manner consistent with the labelling of muscarinic receptors. The addition of pirenzepine or of carbachol to the incubation medium to generate displacement curves was indicative of the presence of M1 and M2 receptors in the right coronary artery. Autoradiography showed the localization of M1 sites primarily in the medial layer of the right coronary artery. M2 sites were located primarily in the adventitia. No [3H]-QNB binding sites were observed in the endothelium. A possible role of muscarinic receptors in the pathogenesis of coronary vasospasm is discussed.

Adolescent

Growth factor (M-CSF) and antigenic properties of macrophages in meningioma.

In meningiomas, transformed meningeal cells can share morphological aspects (in hemangiopericytic meningioma) and antigenic properties (i.e.: HLA-DR antigens expression) with elements of the monocyte/macrophage lineage. In this report, we describe a case of a highly vascular meningioma where numerous tumor cells, studied with immunohistochemical methods, present phenotypic properties of macrophages. Moreover, the cerebrospinal fluid (CF) analysis disclosed, using a biological assay, a high level of a growth factor for monocytic elements, the Macrophages Colony Stimulating Factor (M-CSF). Our findings may confirm that transitional aspects between different mesenchymal cells could be present in meningiomas.

Antigens, CD

Pathologic evidence of extensive left ventricular involvement in arrhythmogenic right ventricular cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (also known as arrhythmogenic right ventricular dysplasia) is characterized by adipose or fibroadipose tissue replacement of the right ventricular myocardium, whereas the left ventricle is substantively spared. Two cases of the disease with evidence of extensive left ventricular involvement at pathologic examination are described. Hearts from two patients who died suddenly showed full-thickness right ventricular fatty infiltration associated with extensive left ventricular involvement (greater than 50% of myocardial thickness). These findings might explain the reported clinical features of left ventricle dysfunction in a subset of patients with arrhythmogenic right ventricular cardiomyopathy. In view of the biventricular involvement of the disease, it should simply be termed "arrhythmogenic cardiomyopathy."

Adipose Tissue

Effect of parenteral administration of GM1 on cytokines and anti-ganglioside antibody patterns. Preliminary report in normal human individuals.

To assess the effects of monosialoganglioside GM1 on some immunological parameters, 12 healthy men were treated with 100 mg GM1 i.m. daily for 15 days. Before and after treatment, the following were studied: (1) serum levels of antibodies against GM1, asialo-GM1 (aGM1), GM2 and GD1b; (2) serum levels of interleukin (IL)-1 beta, IL-2, soluble IL-2 receptor (sIL-2R), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma); (3) IL-1 beta and TNF-alpha production by peripheral blood monocytes (PBMO). Anti-ganglioside antibody and cytokine serum levels were not affected by exogenous GM1 administration with the exception of a transient increase in anti-GM1 antibody titer observed in one subject. In addition, no inhibition of IL-1 beta and TNF-alpha production by PBMO was observed. These preliminary data do not support a potential immunogenic or immunomodulatory function for in vivo administered GM1.

Adolescent

Acute central nervous system infection by Trypanosoma cruzi and AIDS.

The acute infection of the CNS by Trypanosoma cruzi acquired by blood transfusion is uncommon. The concomitance of AIDS in the patient reported shows the importance of cellular immunity in restriction of this parasite, and reinforces the problem of blood transfusion in endemic zones.

Acquired Immunodeficiency Syndrome

[Inflammatory aneurysm of the abdominal aorta: anatomo-clinical study on 16 cases and pathogenetic hypothesis].

BACKGROUND: Inflammatory aneurysms of the abdominal aorta constitute an anatomoclinical entity characterised by prominent thickening and fibrosis of the aneurysmal wall, extending to the adjoining structures. Etiology, pathogenesis and relation with atherosclerosis still remain controversial. METHODS: Sixteen consecutive patients undergoing surgery for inflammatory aneurysm of the abdominal aorta between March 1987 and December 1990 were studied (Group I); as a control, a series of 16 consecutive patients operated on in the same period for atherosclerotic aneurysm of the abdominal aorta was selected (Group II). As far as clinical history and symptoms are concerned, the comparison between the two groups revealed significant differences only for hydronephrosis (exclusively present in Group I, p < 0.05) and abdominal pain (more frequent in Group I, p < 0.01). The microscopic study of the aneurysmal wall was performed by scoring its histological features (atherosclerotic lesions, medial and adventitial fibrosis, inflammatory infiltrates and lymphatic stasis) from 1+ to 3+. RESULTS: As regards the microscopical features, atherosclerotic lesions were present in all the examined cases, whereas periadventitial fibrosis appeared in all the aneurysms of Group I and in none of Group II; the comparison between the two groups revealed further significant differences for extensive intimal calcification (exclusively present in Group II, p < 0.05), fibrous replacement of the tunica media (more thorough in Group I, p < 0.02), and the extent of inflammatory infiltrates (more prominent in Group I, p < 0.05). CONCLUSIONS: From the scarcity of pathognomonic features in both case-history and clinical presentation, the constant coexistence of prominent atherosclerotic lesions, and the progressive trend of the pathologic features, inflammatory aneurysms may be inferred to be a variant of atherosclerotic ones, characterised by a particular prominence of inflammation and fibrosis. The frequent occurrence of dilation of both periaortic lymphatic vessels and lymph node sinuses, even in "incipient" aneurysms, supports the hypothesis that it may be the lymphatic stasis which determines periaortic fibrosis. Finally, atherosclerotic components passing into periaortic fibrosis and eliciting granulomatous reaction were observed in two Group I cases featuring prominent "inflammatory" symptoms; such a finding favours the hypothesis that an immune reaction against some components of the atherosclerotic plaque may lead to the pronounced inflammatory response that is peculiar of inflammatory aneurysms.

Aged

On the role of interleukin-2 (IL-2) in multiple sclerosis (MS). IL-2-mediated endothelial cell activation.

Increased serum levels of IL-2 and sIL-2R can be demonstrated in patients with active MS, a finding that strongly supports the hypothesis of a systemic T cell activation in such patients. However, IL-2 may play a crucial role in MS immunopathology by activating endothelial cells, as suggested by the vascular leak syndrome complicating hrIL-2 therapy. Early BBB impairment and focal perivascular edema that characterize MS lesions may be the effect of an IL-2-induced cytokine cascade.

Blood-Brain Barrier

[The contribution of pathology sections to the Italian Heart Transplant Project in the first 5 years of its activities (1985-1990)].

All the transplantation units within the Italian Heart Transplantation Project are supported by a section of pathology, devoted to the study of the recipient's heart, to patient monitoring by means of a schedule of endomyocardial biopsies, and, if that was the case, to examine the donor's heart and to analyse the causes of death. When successes and failures of the first five years of the Project's activity are weighed up, good results are observed: of the 847 operations performed (orthotopic, heterotopic and heart-lung transplants, and re-transplants) an actuarial survival rate of 77% at 5 years has been achieved. The sections of pathology believe to have contributed significantly to these results, examining as many as 10,446 endomyocardial biopsies. The indications for transplantation were: dilated cardiomyopathy (48.5%); ischemic (35.3%); valvular (5.9%) and congenital (2.4%) heart disease; hypertrophic cardiomyopathy (2.2%); endocardial fibroelastosis (1.7%); restrictive cardiomyopathy (1.4%); anthracycline cardiotoxicity (0.8%); myocarditis (0.8%); cardiac tumours (0.5%) and arrhythmogenic cardiomyopathy (0.2%). Distribution of recipients by sex and age varied according to the indications for transplantation: males were more common among the patients transplanted for ischemic (97%) and valvular (84%) heart disease, as well as for dilated (82%) and hypertrophic (78%) cardiomyopathy, whereas the opposite was true for endocardial fibroelastosis (males constituting 21%) and cardiac tumours (25%). Mean age at transplantation ranged from 49 years (ischemic heart disease) to 6 years (endocardial fibroelastosis). In the follow-up period, a 17.5% death rate was recorded; the main causes of death were the early failure of the transplanted heart (27 pts), postoperative complications (16), hyperacute rejection (4), acute rejection (18), infections (the singular most frequent cause of death, 35 pts), the proliferative endoarteritis of coronary branches (the so-called chronic rejection, that caused 21 deaths and required 14 re-transplants) and the development of neoplasms (11). The actuarial survival curve drops to 89% after the first postoperative month, abates to 82% at the end of the first year, and progressively decreases to 77% at the end of the fifth follow-up year. Rejection monitoring required an average number of 12.5 endomyocardial biopsies per recipient, and allowed 1.7 rejection episodes per patient to be diagnosed. The fewer were the rejection episodes occurring in a unit, the higher was the percentage of deaths due to infections.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors

Herpes simplex pneumonia in a heart transplant recipient.

An unusual case of Herpes simplex virus (HSV) pneumonia in a heart transplant recipient receiving chronic immunosuppressive therapy is reported. This infection presented an indolent course manifested by a chronic left pulmonary infiltrate unresponsive to antibiotic therapy and mild hypoxemia. Death eventually occurred as a consequence of an other infectious complication of the postoperative period. The HSV etiology of the necrotizing pneumonia observed at autopsy was established on the basis of histologic findings.

Adult

Left ventricular outflow tract obstruction in atrioventricular septal defects: a pathologic and morphometric evaluation.

Subaortic stenosis has been described with increasing frequency as an ominous feature of atrioventricular septal defect (AVSD), especially following surgical correction of the anomaly in non-Down's syndrome patients. In order to study the surgical anatomy of the left ventricular outflow tract in this malformation, 48 hearts featuring AVSD were examined. Obstructive lesions were classified into unequivocal forms (class A, 13.5%) and potential ones (class B, 10.8%). In the remaining hearts (class C, 75.7%) no obstruction was noted. In class A, subaortic stenosis was due to exaggeration of the anticipated anomalous arrangement of atrioventricular valve tensor apparatus, to the persistence of a subaortic muscular infundibulum, and to a discrete fibrous diaphragm. A potential for subaortic stenosis is provided by the unwedged position of the aortic valve. The left ventricular outflow tract is transformed into a long, forward-displaced fibromuscular channel. Morphometric analysis showed in AVSD (with both common annulus and separate orifices) a significantly (p less than 0.01) lower inflow/outflow tract ratio, and a significantly (p less than 0.01) lower right ventricular/left ventricular outflow length ratio than normal hearts. These results suggest that AVSD is characterized not only, as commonly stated, by inflow tract shortening, but by outflow tract lengthening as well. On these anatomical grounds, nearly all cases of AVSD could harbor the potential for subaortic stenosis; however, this becomes a real hazard (class B) only when associated with forward displacement of the left anterior papillary muscle, or direct insertion on the ventricular septum of the anterior bridging leaflet, and it may be converted to an actual obstruction by the effects of surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic Valve Stenosis

Prognostic signs in the evolution of premature thelarche by discriminant analysis.

Since premature thelarche (PT) can be a first sign of precocious puberty (PP), the aim of our study was to identify simple items in the course of the first 6 months of follow-up that could help predict if PT would evolve to PP. Thirty-two girls with PT were studied. First evaluation included bone age (BA), basal estradiol, FSH, LH and prolactin. GnRH was performed in 15 subjects and BA was checked at 6 month intervals in 30. Based on clinical outcome after a mean follow-up of 33.4 +/- 16.5 (SD) months, patients were divided into 2 groups: Group I (G-I) included subjects whose breast development either remained unchanged, increased or regressed; Group II (G-II) included subjects who progressed to PP. The multivariate combination of the items which was able to best discriminate between the two groups was chosen in predicting the evolution of PT. The items considered included four variables available at the time of diagnosis [chronological (CA) at onset less than 3 years, basal FSH, basal LH and BA/CA ratio] and two additional variables after a 6-month follow-up (delta BA/delta CA and growth velocity); 88% of G-I and 14% of G-II had CA less than 3 yr. Basal FSH levels were elevated in both G-I (7.6 +/- 3.0 mIU/ml) and G-II (12.1 +/- 4.1) with respect to controls (2.6 +/- 1.2); however, approximately 20% of G-I had low FSH levels. Basal LH levels were consistently higher in G-II (8.0 +/- 1.3 mIU/ml) than in G-I (2.9 +/- 1.5) or controls (2.8 +/- 1.2). Although initial BA was advanced (greater than 2SD) in 21% of G-I and in all of G-II, an acceleration of BA was seen only in G-II. The mean growth velocity of G-I (44.1 +/- 31.5%) was significantly less than G-II (92 +/- 32%; p less than 0.0025). With the help of the discriminant equations derived from data obtained at diagnosis and during the first 6 months of follow-up, all subjects with isolated premature thelarche could be sharply distinguished from those who subsequently progressed to precocious puberty.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

A longitudinal study on IL-2, sIL-2R, IL-4 and IFN-gamma in multiple sclerosis CSF and serum.

The cerebrospinal fluid (CSF) and serum levels of interleukin-2 (IL-2), soluble IL-2 receptor (sIL-2R), interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) were longitudinally investigated in 20 multiple sclerosis (MS) patients. There were 80 paired CSF and serum samples (range 2-8 per patient) covering a 1-5 year (mean 2.5 year) period. Increased levels of IL-2 and sIL-2R were found in 56 and 71%, respectively, of MS sera. In all patients, one or several sera (totally 89%) exhibited values above the normal range for either one of the components or both. The occurrence of IL-2 or sIL-2R positive CSF specimens was much lower, 15 and 9%, respectively. Only 3 MS sera (from one patient) had clearly detectable IL-4 and no CSF samples were definitely positive. IFN-gamma was undetectable in all serum and CSF specimens. No correlations were found between the immunological parameters and the clinical disease activity. The cytokine patterns in MS give strong support for the presence of a systemic T-cell activation. Furthermore, the data argue for a predominant activation of an IL-2- and sIL-2R-producing but not IL-4-producing T-helper (Th) lymphocyte subpopulation, Th1/CD4 + CD45R + cells.

Autoimmune Diseases

Autoradiographic localization of beta-adrenergic receptors in human large coronary arteries.

The distribution of beta-adrenergic receptors in sections of the human right and left coronary arteries and of the anterior intraventricular branch was studied by the use of combined in vitro radioreceptor binding and autoradiographic techniques. [125I]Cyanopindolol was used as a ligand for beta-adrenergic receptors. Binding of the radioligand to sections of the three coronary arteries under study was saturable, stereoselective, reversible, and displaceable by antagonists and agonists with the rank order of potency expected for beta-adrenergic receptors. Analysis of binding isotherms indicated maximum binding capacities of 41.5 fmol/mg protein for the right coronary artery, 35.4 fmol/mg protein for the left coronary artery, and 25.7 fmol/mg protein for the anterior interventricular branch. Dissociation constants were approximately 35 pM in the arteries examined. The relative amounts of beta 1- and beta 2-receptor subtypes were as follows: 72% beta 1-receptors and 28% beta 2-receptors in the right coronary artery; 65% beta 1-receptors and 35% beta 2-receptors in the left coronary artery; 40% beta 1-receptors and 60% beta 2-receptors in the anterior interventricular branch. The results of autoradiographic analysis revealed a predominance of beta 1-receptors in the medial layer. beta 2-Receptors were localized primarily in the adventitia, in the adventitia-media border, and in the intimal layer. These results should lead to a better understanding of the mechanisms involved in the control of coronary circulation in humans.

Adolescent

Electron paramagnetic resonance spectroscopy on isolated rat heart: a technical note.

Spin labels have been measured directly in the isolated rat heart, perfused by the Langendorff method, using a 1500 MHz low frequency electron paramagnetic resonance spectrometer. This apparatus was previously employed to measure spin label pharmacokinetics of nitroxide sensitive to oxygen in whole mice. The heart was introduced in a resonant cavity to measure the uptake and clearance of free radicals. Various kinetic parameters were measured and are discussed, taking into account the features of the Langendorff apparatus.

Animals

Transferrin receptors in rat central nervous system. An immunocytochemical study.

Using an immunocytochemical method we demonstrated the presence of TfR on adult rat neurons, particularly in the cerebral cortex and brain stem. The monoclonal antibody (mab) against rat TfR (clone OX 26) stained neurons of all cortical layers and in the brain stem where the reaction was most evident. Purkinje cells in the cerebellum and scattered neurons in the gray matter of the cervical spinal cord were weakly stained. Choroid plexus cells also reacted with the mab against TfR whereas oligodendrocytes in the cerebral white matter were faintly outlined by the mab. The presence of TfR on endothelial cells of brain capillaries was here confirmed.

Animals

Free light chains of immunoglobulins in the cerebrospinal fluid of human immunodeficiency virus type 1-infected patients.

The presence of immunoglobulin (Ig) free light chains (FLC) was investigated in the cerebrospinal fluid (CSF) of human immunodeficiency virus type 1 (HIV-1)-infected patients. Intrathecal synthesis of FLC was demonstrated in 80% of the patients, even in the absence of oligoclonal Ig. The FLC patterns were characterized by restricted heterogeneity with regard to both isoelectric point and the molecular weight, and were mainly composed by dimers rather than monomers. A striking prevalence of lambda FLC was also observed. Local production of FLC can be taken as a marker of an ongoing immunopathological process within the central nervous system (CNS) in HIV-1-infected patients. A deregulation of Ig production by intrathecally activated B cells may be hypothesized.

Acquired Immunodeficiency Syndrome

Relation of complex ventricular arrhythmias to presenting features and prognosis in dilated cardiomyopathy.

To evaluate whether complex ventricular arrhythmias relate to presenting features and prognosis of dilated cardiomyopathy, 104 patients were studied from 1977 to 1987. At diagnosis, the 19 patients with complex ventricular arrhythmias (18%), as compared to the 85 patients without (82%), had a higher incidence of palpitation (P less than 0.01), severe dyspnea (P less than 0.001) and atrial fibrillation (P less than 0.01). They showed also higher mean right atrial pressures (10 +/- 5 vs 6 +/- 4 mm Hg, P less than 0.001) and higher right ventricular end-diastolic pressures (11 +/- 4 vs. 7 +/- 4 mm Hg, P less than 0.001) than patients without complex ventricular arrhythmias. Histologic samples were collected from the 32 patients (31%) studied since 1984 and semiquantitatively graded. The 11 patients with complex ventricular arrhythmias showed a higher frequency of severe interstitial fibrosis than the 21 patients without (64% vs. 24%, P less than 0.05), but they were otherwise similar as to the frequency of marked myocellular hypertrophy, changes of myocardial regression, endocardial fibrosis, attenuation of myocytes, hyperplasia of smooth muscle cells and infiltration by inflammatory cells. During a follow-up of 3.8 +/- 3.5 years, 35 patients (34%) died. Mortality was 58% (11 out of 19) in patients with complex ventricular arrhythmias and 28% (24 out of 85) in patients without (P less than 0.025). These results show that complex ventricular arrhythmias in dilated cardiomyopathy are associated with impairment of function of the right heart and severe interstitial fibrosis of the left ventricle, rather than with left ventricular dysfunction. Presence of complex ventricular arrhythmias also seems to identify those at high risk for death.

Adult