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Biomedical subjects

Alberto Ricci

Publications and source records attributed to Alberto Ricci.

16 recordsLinked to original sources

Neurotrophin system expression in human pulmonary carcinoid tumors.

Neurotrophin (NT) and NT receptor expression was assessed in 12 typical (TC) and 8 atypical (AC) human pulmonary carcinoids by Western blot and immunohistochemistry. TC and AC carcinoid express to different extent NT and NT receptor proteins. Nerve growth factor (NGF) was expressed by 83% of the TC but not by the AC carcinoids. Brain derived neurotrophic factor (BDNF) was expressed by 33 and 100% of TC and AC carcinoids, respectively. NT-3 was expressed by 58% of the TC and 38% of AC carcinoids. TC carcinoids express high affinity NT receptors while 50% of the AC carcinoids express the TrkB receptor. Our results demonstrate that NGF/TrkA and BDNF/TrkB signaling need to be considered as regulatory pathways that may address survival, differentiation and/or aggressiveness of human pulmonary carcinoids. Contrarily to the BDNF/TrkB, expression of the NGF/TrkA signaling may overcome aggressiveness of carcinoid cells. NTs may be useful as markers in the clinic.

Adult↗

Neurotrophin system activation in bronchoalveolar lavage fluid immune cells in pulmonary sarcoidosis.

BACKGROUND AND AIM OF THE STUDY: Pulmonary sarcoidosis is a chronic granulomatous disease characterized by macrophage and CD4+ T-cell accumulation at the site of inflammation. Analysis of the cytokine network has substantially improved knowledge on immunopathogenesis of sarcoidosis. We hypothesize that neurotrophins (NTs), nerve growth factor (NGF), brain derived neurotrophic factor (BDNF) and NT-3, besides their importance in immune system activities, participate in chronic inflammatory disorders and in repair processes. METHODS: The expression of NTs and NT receptors was assessed in broncho alveolar lavage (BAL) macrophages, CD4 and CD8 T-cells, from 10 patients with pulmonary sarcoidosis, using molecular biology, Western blotting and immunocytochemistry. RESULTS: Increased levels of NTs and of high affinity NT receptor (Trks) transcripts and proteins in BAL macrophages, CD4+ and CD8+ T-cells from pulmonary sarcoidosis patients were demonstrated in comparison with healthy controls. Contrarily to healthy controls, in pulmonary sarcoidosis the expression of NGF was increased in alveolar macrophages as well as NGF and BDNF in CD4+ and CD8+ T-cells. An increased expression of TrkA, TrkB and TrkC receptors was also noticeable. Furthermore, BDNF expression in alveolar macrophages and NT-3 expression in the three different BAL immune cell populations investigated were induced during sarcoidosis. A significant correlation was observed between CD4:CD8 ratio, lymphocytosis, radiological stage and CD4 and CD8 NT expression. CONCLUSIONS: These findings suggest that NTs are exaggeratedly expressed in BAL immune cells in pulmonary sarcoidosis and may participate in the progression of disease modulating immune cell functions.

Adult↗

Elevated neurotrophin and neurotrophin receptor expression in spontaneously hypertensive rat lungs.

Spontaneously hypertensive rats represent a widely used animal model of hypertension. Altered neurotrophin regulation has been related to systemic hypertension. Lung cells synthesize and release neurotrophins(NT) which are involved in several pulmonary disturbances. Our study explored the expression of NT and their receptors using molecular biology and immunohistochemistry. Spontaneously 6-, 20- and 29- weeks hypertensive (SHR) and Wistar Kyoto rat (WKY) lungs were used. SHR and WKY lungs expressed neurotrophin and neurotrophin receptor mRNAs and protein transcripts. Age and hypertension dependent increase was clearly noticeable. Furthermore, immunohistochemistry revealed that their increase was mainly noticeable within bronchial and vascular components of the lung. Although the role of NT in sympathetic hyperinnervation and progression of systemic hypertension is a well established phenomenon, their increase in SHR lungs, strongly suggest that NT may be operative during pulmonary hypertension and in subsequent airway and pulmonary vascular remodeling.

Animals↗

Pulmonary alveolar microlithiasis: report on 576 cases published in the literature.

BACKGROUND AND AIM OF THE WORK: Pulmonary alveolar microlithiasis (PAM) is a rare disease characterized by intra-alveolar calcium deposits. The etiology of the disease is still unknown and many authors have supposed that an inherited local enzymatic defect is responsible for calcium deposition. The present paper aimed to study the disorder throughout the world, emphasizing the diagnostic and therapeutic views. METHODS: All the papers published on this subject in the literature were reviewed. RESULTS: Cases studied were 576 and most of them came from Europe (42.7%) and Asia (40.6%). The countries involved were fifty-one and twelve of them were attributed with at least ten cases each (Bulgaria, France, Germany, India, Italy, Poland, Spain, Russia, Japan, Turkey, USA, ex-Yugoslavia). Symptoms were absent in more than half the patients; dyspnoea, cough and chest pain were reported in the other cases. Family history for the disease was found in one-third of the patients. Chest x-rays and computed tomography were so characteristic that they were enough to diagnose the disease even if microscopic evidence of the microliths into the alveoli was obtained in most cases (e.g. by biopsy, autopsy, bronchoalveolar lavage). Pulmonary tuberculosis or sarcoidosis were misdiagnosed in 88 cases out of the 576. The course of the disease was slow and patients usually died as a result of cardio-respiratory failure. CONCLUSIONS: This review of PAM has shown that the etiology of the disease is still unknown, it is widespread throughout the world and easy to diagnose; it develops slowly and therapy is ineffective except for lung transplantation.

Adolescent↗

Neurotrophin and neurotrophin receptor protein expression in the human lung.

Neurotrophins (NTs) promote survival and differentiation of central and peripheral neurons, and display several activities also in non-neuronal cells. Human lungs synthesize and release NTs, which are probably involved in the pathophysiology of pulmonary disturbances. In this article the expression and anatomic localization of nerve growth factor, brain-derived neurotrophic factor, and NT-3 and of corresponding high-affinity receptors TrkA, TrkB (full-length and truncated [TR-] isoforms), TrkC, and of the low-affinity p75 receptor, were assessed in surgical samples from adult human lung by reverse transcriptase-polymerase chain reaction, Western blot, and immunohistochemistry. NTs and their cognate receptor mRNA and protein transcripts were detected by reverse transcriptase-polymerase chain reaction and immunoblotting, respectively, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) mRNA and corresponding protein transcripts being the most expressed. High levels of TrkB-[TR-] mRNA and of its protein transcript were also demonstrated, whereas a low expression of p75 mRNA and of corresponding protein transcript were found. Microanatomic analysis of immunohistochemical study revealed that bronchial epithelial cells were immunoreactive for different NTs, with a higher intensity of BDNF immune staining compared with other NTs, but did not express NT receptor immunoreactivity. Alveolar cells were immunoreactive for TrkA and TrkC receptor protein, but did not display immunoreactivity for NTs or other receptors investigated. Gland cells expressed NT and high-affinity NT receptor immunoreactivity, but not p75 receptor immunoreactivity. NT and low-affinity receptor immunoreactivity was observed within neurons and satellite cells of parasympathetic ganglia as well as in nerve fiber-like structures supplying the bronchopulmonary tree. An obvious immunoreactivity for NTs and NT receptor protein was also observed in intrapulmonary branches of pulmonary artery. Pulmonary lymphocytes and macrophages express nerve growth factor and high-affinity NT receptor immunoreactivity. The role of NTs in non-neuronal tissue including lung has not been clarified yet. The widespread expression of NTs and their receptors in different components of the lung suggests that these factors may contribute to regulate cell function in human lung.

Aged↗

[Legionnaire's pneumonia with rhabdomyolysis and acute renal failure. A case report].

Legionella pneumophyla is the agent responsible of Legionnaire's disease. It appears as a severe pneumonia and often requires admission in Intensive Care Unit. In literature, renal failure is reported to occur in 15 percent of Legionnaire disease and this event induce a mortality over 50% of these cases. The authors describe a case of Legionnaire's pneumonia with respiratory failure, rhabdomyolysis and acute renal failure. Patient was a female, 61 yrs old, admitted to our hospital because of fever (38 degrees-38.5 degrees C), severe respiratory failure (pH = 7.49, PaCO2 = 23.1 mmHg, PaO2 = 56.7 mmHg), oliguria (< 200 ml/24 h); chest x-rays and computed tomography (TC) showed a pneumonia at right lower lobe. Among other things, in blood analysis was noted the following values: BUN = 47 mg/dl, creatinine = 2.1 mg/dl, Na+ = 133 mmol/L, Cl- = 97 mmol/L, Ca+ = 7.2 mg/dl, K+ = 5.8 mmol/L, AST = 213 U/L, ALT = 45 U/L, LDH = 1817 U/L, CPK = 16738 U/L, CPK-MB = 229 U/L, myoglobin > 4300 ng/ml., leucocyte count = 17,500/mmc (N = 92%, L = 3%, M = 5%), positive anti Legionella IgG and IgM (IgG > 1:64, IgM > 1:96), evidence of Legionella soluble antigen in the urine analysis. Therapy with clarytromicyne (500 mg b.i.d i.v.) and rifampicin (600 mg/die i.v.) was begun; computed tomography showed after six days an improvement of pulmonary lesion but, in the following days, health status and blood analysis got worse. Patient went on antibiotics and underwent haemotherapy (Hb: 8 gr/dl), haemodialysis because of acute renal failure but healthy status worse furthermore and she died on 18th days after admission. This case point out rhabdomyolysis with acute renal failure is suggestive for Legionnaire's disease and is associated with high rate of mortality.

Acute Kidney Injury↗

Postnatal development of dopamine receptor expression in rat peripheral blood lymphocytes.

Postnatal development in the expression of dopamine D1-like and D2-like receptors was investigated in peripheral blood lymphocytes of male Wistar rats aged 1, 3, 4, 8, 12 and 16 weeks of age by radioligand binding assay techniques. Sample of frontal cortex, striatum and hippocampus were also investigated as reference tissues. The dopamine D1-like receptor antagonist [3H]SCH 23390 and the dopamine D2-like receptor agonist [3H]7-OH-DPAT were used as radioligands. The affinity (K(d)) of [3H]SCH 23390 or of [3H]7-OH-DPAT binding was unchanged in lymphocytes of rats of different age groups. The density (B(max)) of [3H]SCH 23390 binding sites increased from the 1st to the 3rd week of age, remained constant from the 3rd to the 8th week of age, and then increased slightly at 12 and 16 weeks of age. The B(max) value of [3H]7-OH-DPAT binding to lymphocytes increased from the 1st to the 3rd week of age, remained constant from the 3rd to the 4th week, increased again until the 12th week and then plateaued. Dopamine D1-like and D2-like receptor maturation in frontal cortex, hippocampus and striatum revealed an increased receptor density until the 4th week of age and a relative stabilization of receptor density values between the 4th to the 12th week depending on the area considered. Comparatively postnatal maturation of lymphocyte dopamine D1-like receptors displayed a pattern different from that of brain areas investigated, whereas maturation of D2-like receptors displayed a pattern similar to that of striatum. The quantitative and/or qualitative dissimilarities between development of lymphocyte and brain dopamine receptors suggest that from a developmental point of view lymphocyte dopamine receptors probably cannot be considered as a marker of homologous brain receptors.

Aging↗

Age-related changes of dopamine receptor protein immunoreactivity in the rat mesenteric vascular tree.

Dopamine D1-D5 receptor protein immunoreactivity and tyrosine hydroxylase (TH) immunoreactivity were investigated on the mesenteric arterial tree by immunohistochemistry. The density of various dopamine receptors and TH immunoreactivity was compared between young (6-month-old), adult (15-month-old) and senescent (24-month-old) Fischer 344 rats by computer-assisted microdensitometry. The dopamine D1-like (D1 and D5) receptors were localized on the tunica media of different sized mesenteric artery branches. The D2-like (D2, D3 and D4) receptors as well as TH immunoreactivity were localized only on the adventitia-media transitional zone of mesenteric arterial tree. Expression of the D1 and D5 receptors was decreased in both adult and senescent rats compared to the young rats, suggesting an age-related decline in these receptors. Of the D2-like receptors, the expression of the D2 receptor was decreased as a function of age, while the D3 receptor was unchanged in the senescent rats compared to the young rats. Expression of the D4 receptor was increased in adult, but was unchanged in the senescent rats compared to young animals. TH immunoreactivity was increased as a function of age. The above data suggest that reduction in the D1, D2 and D5 receptor expression may contribute to the deficiency in the dopamine-mediated vasorelaxation and hence blood flow in the mesenteric vascular tree in aging. The different sensitivity to aging of sympathetic neuroeffector junctions labeled by TH and of dopamine D2-like receptors that are known to be prejunctional, suggests that age-related changes of dopamine receptor expression in the mesenteric vasculature reflect more complicated mechanisms than simple up- or down-regulation phenomena.

Aging↗

Expression of peripheral blood lymphocyte muscarinic cholinergic receptor subtypes in airway hyperresponsiveness.

The expression of muscarinic cholinergic receptor subtypes was investigated in peripheral blood lymphocytes (PBL) of bronchial asthma patients by a combined kinetic and equilibrium labeling technique for radioligand binding assay of muscarinic cholinergic receptor subtypes and by receptor immunochemistry and immunocytochemistry. An increased expression of M2 and to a lesser extent of M5 receptors and no changes of M4 receptor were observed in PBL of asthmatics compared to control individuals. The increase was related to bronchial hyperresponsiveness detected by methacholine challenge test. Analysis of M3 receptor expression revealed biphasic changes, with a decreased receptor density in patients with normal, mild and moderate responses to methacholine test and a recovery to levels similar to those found in healthy individuals in severe responders to methacholine test. The demonstration of a different expression of lymphocyte muscarinic receptors in asthma suggests that cholinergic system may participate to a molecular framework influencing immune functions in asthma.

Acetylcholine↗

Immunochemical and immunocytochemical characterization of cholinergic markers in human peripheral blood lymphocytes.

Cholinergic markers and the expression of M(2)-M(5) muscarinic cholinergic receptor subtypes were investigated in human peripheral blood lymphocytes by Western blot analysis and immunocytochemistry. The totality of peripheral blood lymphocytes express acetylcholine (ACh) immunoreactivity, choline acetyltransferase (ChAT), acetylcholinesterase (AChE), vesicular ACh transporter (VAChT) and M(2)-M(5) muscarinic cholinergic receptor protein immunoreactivity. Western blot analysis performed independently on T and B lymphocytes using anti-ChAT and anti-AChE antibodies revealed labelling of single bands of approximately 68-70 and 70 kDa, respectively, whereas VAChT was bound to two bands of approximately 80 and 45 kDa. The pattern of immunoblotting was similar in membranes of lymphocytes and striatum, used as a reference brain tissue. Western blot analysis using anti M(2)-M(5) receptor antibodies revealed labelling of single bands of approximately 55, 85-90, 50 and 81 kDa, respectively. Confocal laser immunofluorescence showed the localization of ACh and VAChT immunoreactivity in punctiform areas likely corresponding to cytoplasmic vesicles. ChAT and AChE were diffused to the cytoplasm and plasma membrane. Muscarinic receptor immunoreactivity was located in lymphocyte plasma membrane. Although the role of lymphocyte cholinergic system is still unclear, the demonstration of cholinergic markers in T and B human blood lymphocytes supports the view that a cholinergic systems may contribute to the regulation of immune function. The characterization of these cholinergic markers may also contribute to define if their evaluation can be used for assessing the status of brain cholinergic system.

Acetylcholine↗

Dopamine D4 receptor expression in rat kidney: evidence for pre- and postjunctional localization.

Dopamine D4 receptors mediate inhibition of vasopressin-dependent sodium reabsorption by dopamine in collecting tubules. At present, the distribution of D4 receptors in other renal districts remains an open issue. The renal distribution of D4 receptor was assessed in normally innervated and denervated male Sprague-Dawley rats by quantitative immunohistochemistry using an anti-dopamine D4 receptor rabbit polyclonal antibody. D4 receptor protein immunoreactivity was observed perivascularly in the adventitia and the adventitia-media border. The density of perivascular dopamine D4 receptor was higher in afferent and efferent arterioles than in other segments of the renal vascular tree. Renal denervation abolished perivascular dopamine D4 receptor protein immunoreactivity. In renal tubules, the epithelium of collecting tubules showed the highest dopamine D4 receptor protein immunoreactivity, followed by the epithelium of proximal and distal tubules. No dopamine D4 receptor protein immunoreactivity was observed in the epithelium of the loop of Henle. Denervation did not change dopamine D4 receptor protein immunoreactivity in renal tubules. These results indicate that rat kidney expresses dopamine D4 receptors located both prejunctionally and nonprejunctionally in collecting, proximal, and distal tubules. This suggests that the dopamine D4 receptor may be involved in the control of neurotransmitter release and in renal hemodynamic and tubule function.

Animals↗

Neurotransmitter receptor expression by peripheral mononuclear cells: possible marker of neuronal damage by exposure to radiations.

Peripheral mononuclear cells (PMC) express several neurotransmitter systems. Increasing evidence suggests that PMC neurotransmitter receptors are involved in modulating immune responses. It is also thought that expression of PMC neurotransmitter receptors may reflect the status of homologous brain receptors. A problem encountered with assay of PMC neurotransmitter receptors was in developing techniques suitable for their assessment in spite of low density. In this paper we summarized findings on the expression of alpha1-adrenoceptor and dopamine receptor subtypes in human peripheral blood lymphocytes characterized by radioligand binding assay techniques and immunocytochemistry. Human lymphocytes express alpha1A-, alpha1B- and alpha1D-adrenoceptor subtypes and dopamine D3, D4 and D5 receptors. Compared to radioligand binding assay, immunocytochemistry applied to cytospin-centrifuged peripheral lymphocytes allowed to assay receptor subtypes investigated in small amounts of blood. The development of sensitive and reproducible techniques for assaying PMC neurotransmitter receptor subtypes even in small amounts of blood such as those used for diagnostic purposes may allow to analyze their sensitivity to different conditions including radiation exposure.

Adult↗

Time intervals (3' or 5') between dose steps can influence methacholine challenge test.

Bronchial hyperresponsiveness (BHR) is a common feature in the majority of asthmatic subjects and methacholine is the most frequently used agent for the test. The influence of 3 or 5 min time intervals between doses steps in a double methacholine challenge test (MCH-3' or MCH-5') was investigated. Using the MCH-3' challenge, 52 intermittent asthmatics were classified as having moderate (BHR-M; 18 subjects), mild (BHR-m; 19 subjects), or bordeline (BHR-B; 15 subjects) BHR. The cumulative dose and the PD20FEV(1) were higher for MCH-5' compared with MCH-3' in BHR-m (p < 0.05) and BHR-B (p < 0.05) but not in the BHR-M group. Also the dose response slopes, FEV(1)% decline/cumulative methacholine dose, calculated for the two challenge tests were statistically different only in BHR-m (p < 0.05) and BHR-B (p < 0.01). At MCH-5', there were 16 subjects with BHR-M, 18 with BHR-m, 12 with BHR-B and 6 subjects with normal reactivity. Results may suggest that in the group of BHR-m and BHR-B subjects, at MCH-5' compared with MCH-3', the cumulative effect of the administered drug, quickly metabolized by cholinesterase, is not complete, thus leading to an incorrect estimation of bronchial hyperresponsiveness degree. It is hoped that time interval between doses be standardized to ensure maximum comparability within and between subjects in challenge tests.

Adult↗

Neuronal populations of rat cerebral cortex and hippocampus expressed a higher density of L-type Ca 2+ channel than corresponding cerebral vessels.

Dihydropyridine (DHP)-type Ca2+ antagonists block primarily L-type Ca2+ channels and are used in the therapy of hypertension. They were also proposed for the treatment of several central nervous system disorders. In brain, these compounds bind both neuronal and vascular Ca2+ channels, but no studies have evaluated comparatively their density at neuronal and vascular level. This study has analyzed the pharmacological profile and the anatomical localization of L-type Ca2+ channels in rat frontal cortex, hippocampus and in forebrain pial and intracerebral arteries by radioligand binding assay and high resolution light microscope autoradiography. The DHP derivative [3H]nicardipine was used as a radioligand. Binding of [3H]nicardipine was consistent with the labeling of L-type Ca2+ channels. In frontal cortex, the highest density of binding sites was found in nerve cell body region, followed by the neuropil and the wall of intracerebral arteries. In hippocampus, the density of binding sites was higher in the nerve cell body region than in the neuropil of CA1, CA3, and CA4 subfields. In the dentate gyrus, a higher density of silver grains was developed in neuropil than in nerve cell body of granule neurons. With the exception of dentate gyrus, neuronal binding sites were more expressed than vascular binding sites in the hippocampus. In pial arteries [3H]nicardipine binding density decreased concomitant with the reduction of vessel diameter, whereas in intracerebral arteries [3H]nicardipine binding density displayed an opposite pattern. The above findings indicate that in brain the density of neuronal L-type Ca2+ channels was significantly higher than that of vascular ones. This may account for more pronounced neuronal than vascular effects after pharmacological manipulation of cerebral Ca2+ channels.

Animals↗

Reversibility test in the early stages of bronchial asthma.

In the early stages of bronchial asthma, it is frequent to find subjects with a positive history and an FEV1 or FEV1/FVC > 80% of the predicted value. This study investigated if the test of reversibility showed a reversible airway obstruction (RAO) in 291 subjects with the above clinical and functional features. Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and expiratory flows (PEF, MEF50, FEF(25-75)) were registered before and 20 minutes after salbutamol administration (200 mcg by MDI). Of 291 subjects, FEV1 increased in 73 (25%) after bronchodilator > or = 12% compared to baseline; the number of subjects with a > or = 35% increase in MEF50 or FEF(25-75) were similar in terms of percentage (respectively, 29.2% and 29%), whereas those with increases in FVC (> or = 12%) and in PEF (> or = 15%) were significantly lower (respectively, 2.7% and 12.3%). The percentage of subjects with RAO (FEV1 increase after bronchodilator > or = 12%) was lower (12%) in the subgroup (108 subjects), with an MEF50 > or = 70% of the value predicted at the baseline assessment, and higher (36%) in the subjects of the subgroup (183 subjects) with an MEF50 < 70%. In conclusion, it is advisable to carry out reversibility tests in all subjects with symptoms indicative of asthma even if their functional tests are "normal" because in a considerable number of cases the RAO was found to confirm the suspected diagnosis and provided a more reliable classification of the disease.

Adrenergic beta-Agonists↗