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Biomedical subjects

A Mangoni

Publications and source records attributed to A Mangoni.

At least 19 recordsLinked to original sources

Adenovirus-mediated VEGF(165) gene transfer enhances wound healing by promoting angiogenesis in CD1 diabetic mice.

It has been previously shown that vascular endothelial growth factor (VEGF) plays a central role in promoting angiogenesis during wound repair and that healing-impaired diabetic mice show decreased VEGF expression levels. In order to investigate the potential benefits of gene therapy with growth factors on wound repair, a replication-deficient recombinant adenovirus vector carrying the human VEGF(165) gene (AdCMV.VEGF(165)) was topically applied on excisional wounds of streptozotocin-induced diabetic mice. Treatment with AdCMV.VEGF(165) significantly accelerated wound closure when compared with AdCMV.LacZ-treated, as well as saline-treated control mice, by promoting angiogenesis at the site of injury. Our findings suggest that AdCMV.VEGF(165) may be regarded as a therapeutic tool for the treatment of diabetic ulcers.

Adenoviridae↗

Clinical aspects of the AIDS dementia complex in relation to histopathological and immunohistochemical variables.

To correlate cerebral histopathological and immunohistochemical changes in the neuroclinical features of the AIDS dementia complex (ADC), autopsy results of 28 ADC patients were related, in a retrospective analysis, to scores on a standardised neurological examination performed at neurologic onset. From a histopathological point of view, the cases were classified as follows: 9 cases of HIV leucoencephalopathy (HIVL; diffuse myelin damage and rare microglial nodules), 7 cases of HIV encephalitis (HIVE; several microglial nodules and no myelin damage) and 12 cases of mixed HIVL and HIVE (HIVL-E). The groups differed significantly with respect to symptoms and CD4 count at neurologic onset, survival and neurological impairment. Immunohistochemically, the interstitial component (p24-positive cells scattered singly within the white matter) was significantly more prevalent in HIVL, and the micronodular component (p24-positive cells confined within microglial nodules) in HIVE. Neurological damage was worse in cases with a high prevalence of interstitial component or a low prevalence of micronodular component. HIVE, HIVL and HIVL-E are distinct clinical forms of ADC. Neurological impairment is related to white matter damage.

AIDS Dementia Complex↗

Retinoids induce fibroblast growth factor-2 production in endothelial cells via retinoic acid receptor alpha activation and stimulate angiogenesis in vitro and in vivo.

The effect of retinoic acid (RA) on endothelial cells is still controversial and was examined in the present study. In bovine aortic endothelial cells (BAECs), all-trans RA (ATRA) and 9-cis RA (9CRA), but not 13-cis RA (13CRA), induced fibroblast growth factor-2 (FGF-2) production and exhibited a biphasic dose-dependent effect to enhance BAEC proliferation and differentiation into tubular structures on reconstituted basement membrane proteins (Matrigel); both processes were inhibited by FGF-2-neutralizing antibody. The pan RA receptor (RAR)-selective ligand (E)-4-[2-(5,5,8,8,-tetramethyl-5,6,7,8-tetrahydro-2-naphtalenyl)-1-propenyl] benzoic acid and the RARalpha-selective ligand 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphtyl)-ethenyl] benzoic acid stimulated the production of FGF-2, whereas the addition of the RARalpha-antagonist RO 41-5253 inhibited this effect. In BAECs, the forced expression of RARalpha, but not RARbeta or RARgamma, enhanced FGF-2 production, whereas the RARalpha-dominant negative, Delta403, blocked this effect. Furthermore, RARalpha overexpression directly stimulated BAEC differentiation on Matrigel and potentiated the effects of ATRA in this assay. Finally, ATRA-treated BAECs coinjected with Matrigel subcutaneously in mice induced neovascularization within the Matrigel plug, and ATRA also enhanced angiogenesis in the chicken chorioallantoic membrane assay. In conclusion, RA can stimulate endothelial cell proliferation and differentiation in vitro via enhanced RARalpha-dependent FGF-2 production, and it can also induce angiogenesis in vivo. The full text of this article is available at http://www.circresaha.org.

Animals↗

Descending and ascending spinal cord evoked potentials from oesophago-vertebral electrical stimulation in normal awake man.

Electrical stimulation of the spinal cord at C7D1 evoked triphasic descending spinal cord evoked potentials (DSCEP) from an oesophago-vertebral recording at D8D8 or D1OD1O. Ascending SCEPs (ASCEP) larger and similar in shape were also observed when the orientation of the stimulating and recording dipoles was reversed. Both SCEPs are in part generated by descending and ascending synchronous excitation of neuronal volume-conducted spinal cord dipoles.

Adult↗

Ecdysteroids from the caribbean sponge Iotrochota birotulata.

The sterol composition of the Caribbean sponge Iotrochota birotulata was investigated. Structure of a new ecdysteroid 2beta,3beta,14alpha, 20beta-tetrahydroxy-22alpha-(2-hydroxyacetiloxy)-5b eta-colest-7-en-6- one (1) was assigned on the basis of spectroscopic and chemical evidence and molecular mechanics calculations. Isolation of the widespread ecdysteroids 2-5 is also reported.

Animals↗

Induction of interleukin-1beta and interleukin-6 gene expression in hypoperfused skeletal muscle of patients with peripheral arterial disease.

BACKGROUND: A growing amount of data supports the role of inflammation in the pathophysiology of atherosclerotic diseases but the cellular source of cytokines has not been clearly identified. Cytokines could be produced by inflammatory cells, activated endothelial and smooth muscle cells, and by the tissue exposed to recurrent ischemia. Accordingly, we evaluated whether hypoperfusion induces gene expression of interleukin (IL)-1beta and IL-6 in the skeletal muscle of patients with peripheral arterial disease and critical limb ischemia. METHODS: Skeletal muscle biopsies were obtained, during a femoral-distal bypass, from normoperfused (control) and hypoperfused skeletal muscles in 8 patients. Gene expression was assessed by semiquantitative reverse transcriptase-polymerase chain reaction, using glyceraldehyde-phosphate-deydrogenase mRNA levels as a normalization factor. RESULTS: In the hypoperfused biopsies, the level of IL-1beta gene expression was significantly higher in all but 2 patients (mean upregulation > 8.8 fold, p = 0.043), and the level of IL-6 gene expression was significantly higher in all but 1 patient (mean upregulation > 23.7 fold, p = 0.031). CONCLUSIONS: We report that IL-1beta and IL-6 gene expression is markedly upregulated in hypoperfused skeletal muscle of patients with critical lower limb ischemia. To our knowledge this is the first report of a local activation of the inflammatory cascade at the level of hypoperfused skeletal muscle. This activation, which could worsen symptoms and tissue viability and be involved in the pathophysiology of reperfusion injury, might be considered as a therapeutic target. It remains to be investigated whether our results may also apply to coronary artery disease.

Aged↗

Glycolipids from sponges. VII. Simplexides, novel immunosuppressive glycolipids from the Caribbean sponge Plakortis simplex.

The new glycolipids simplexides (1) have been isolated from the marine sponge Plakortis simplex, and their structure determined by spectroscopic data and microgram-scale chemical degradation. Simplexides are composed of long-chain secondary alcohols glycosylated by a disaccharide chain, and represent a new structural kind of glycolipids. Simplexides strongly inhibit proliferation of activated T-cells by a non-cytotoxic mechanism and can be regarded as simple model molecules for designing immunosuppressive drugs.

Animals↗

Immunohistochemical study of fatty acid synthase, Ki67, proliferating cell nuclear antigen, and p53 expression in hyperplastic parathyroids.

Patients with secondary hyperparathyroidism following chronic renal disease frequently develop hyperplastic parathyroids. Hyperplastic parathyroids have an increased number of chief cells, a decreased amount of stromal fat, and a nodular or diffuse histologic pattern. Hyperplastic parathyroids may also express higher proliferative activity compared with controls. We evaluated the morphologic features and immunohistochemical expression of fatty acid synthase (FAS), Ki67, proliferating cell nuclear antigen, and p53 protein in 78 hyperplastic parathyroids from 20 patients with secondary hyperparathyroidism. Twenty normal parathyroids incidentally removed during nonneoplastic thyroid surgery were used as controls. Our results showed that hyperplastic glands overexpress FAS (P =.06). Statistical analysis also revealed a significant association between FAS and p53 protein (P =.006) and between FAS and hyperplastic glands with a predominant nodular pattern (P =.02). Hyperplastic parathyroids from patients with chronic renal failure strongly express FAS. Fatty acid synthase may therefore be a potential biological indicator of highly proliferating parathyroid cells.

Adult↗

Assessment of cognitive function in asymptomatic HIV-positive subjects.

This retrospective study aims to assess cognitive involvement in pre-AIDS, not drug abuser subjects and to determine whether CD4 status or disease stage best correlates with cognitive changes that may portend development of ADC. 328 cases were analyzed. No differences in psychometric performance in relation to CDC stage were found. Instead, patients with CD4 < 200/microl performed worse overall, with a statistically significant difference for Digit Symbol, Corsi Test, Block Design and HIVDA Scale. Even if cognitive decline is not evident in the early phase of HIV infection, CD4 count seems the more sensitive early indicator of cognitive changes adequately pointed out by the HIVDA Scale, which could be considered a useful screening tool for cognitive deficit.

AIDS Dementia Complex↗

Muscle compound motor action potentials from esophago-vertebral electrical stimulation of the spinal cord in the normal awake man.

In 15 normal alert subjects, electrical stimulation of the spinal cord at various levels by a nasopharyngeal probe (cathode) and a vertebral surface electrode (anode) was performed with different orientation of the stimulating dipole. Maximum spinal cord compound motor action potentials (SCCMAPmax) simultaneously recorded from homologous muscles of the upper arm of both sides were not significantly different in amplitude and latency. By stimulating the spinal cord at the cervico-dorsal level it was possible to obtain simultaneous recordings of SCCMAP from muscles of the upper and lower limbs and trunk at a stimulus intensity of 50-70 mA. Stimulating the spinal cord and the peripheral nerve at Erb's point it was also possible to calculate motor propagation velocity of the peripheral nerve of limb-girdle muscles. Central latency of the F wave exceeded by 0.5 to 0.7 ms that of the SCCMAP, suggesting that esophago-vertebral stimulation is able to directly excite the motor neurons. By threshold current intensity, it is possible to obtain a threshold SCCMAP (SCCMAPth) of the same latency as SCCMAPmax and different in shape, duration and amplitude from the CMAP obtained by cortical stimulation with threshold magnetic stimuli. SCCMAPth was different in shape from the motor unit action potential activated at weak voluntary effort, SCCMAPth latency and amplitude were unchanged after voluntary homo- and contralateral activation.

Action Potentials↗

Light chain deposition disease neuropathy resembling amyloid neuropathy in a multiple myeloma patient.

A 65-year-old man with IgG lambda multiple myeloma developed severe polyneuropathy with prominent thermal-pain sensory impairment and autonomic failure. Although the clinical presentation suggested amyloid neuropathy, nerve biopsy showed the immunohistochemical and ultrastructural features typical of light chain deposition disease (LCDD). A precise morphologic and clinical description of LCDD neuropathy is given for the first time in the present report.

Aged↗

Prevalence of subclinical neuropathy in diabetic patients: assessment by study of conduction velocity distribution within motor and sensory nerve fibres.

Nerve conduction velocity distribution (CVD) study is a newly-developed electrodiagnostic method for detecting alterations in the composition of nerve fibres according to their conduction velocity. The presence of subclinical neuropathy was evaluated in 138 diabetic patients by CVD study of four motor nerves (external popliteal and ulnar nerves bilaterally) and two sensory nerves (median nerve bilaterally), and the data obtained were compared with standard electrophysiological parameters in the same nerve segments. CVD studies revealed an altered distribution pattern in 106 of 129 evaluable patients for motor nerves (82%) and in 67 of 115 evaluable patients for sensory nerves (58%), while standard examination gave abnormal findings in 92 of 137 patients (67%) and in 33 of 118 patients (11%), respectively. Of the patients adequately evaluated by both techniques, 21 of 129 patients (16%) revealed altered CVD data unaccompanied by slowing of maximum nerve conduction velocity, and 37 patients of 101 (37%) showed similar findings for sensory nerves. Subclinical alterations of motor and sensory nerve CVD were not significantly related to age or to metabolic control expressed as glycated haemoglobin levels; a significantly longer duration of disease was found in patients with motor and mixed subclinical neuropathy with respect to non-neuropathic patients. The CVD study allowed us to detect subclinical abnormalities of motor and sensory nerve fibres; often this is a more sensitive method than the standard electrodiagnostic study. This method can be very useful as a diagnostic tool and in research in the study of the progression of diabetic neuropathy.

Adolescent↗

New 9,11-secosterols from gorgonia Subergorgia suberosa of the Indian Ocean.

Three new 9,11-secosterols, 3 beta,6 alpha,11-trihydroxy-9,11-seco-5 alpha-cholest-7-ene-9-one (1), 24S- (2a), and 24R-methyl-3 beta,6 alpha, 11-trihydroxy-9,11-seco-5 alpha-cholest-7,22E-diene-9-one (2b), were isolated from the Indian Ocean gorgonia, Subergorgia suberosa. Their structures were established by spectroscopic data.

Animals↗

Microglial nodular encephalitis and ventriculoencephalitis due to cytomegalovirus infection in patients with AIDS: two distinct clinical patterns.

In patients with AIDS, cerebral infection due to cytomegalovirus (CMV) results in two distinct neuropathological patterns: microglial nodular encephalitis (MGNE) and ventriculoencephalitis (VE). In order to identify clinical features to facilitate the differential diagnosis of these two forms of CMV encephalopathy in living patients, we retrospectively reviewed the clinical records of 18 patients with MGNE or VE diagnosed at autopsy. We identified the following clinical features as distinguishing the two encephalopathies: (1) MGNE manifests earlier than VE; (2) the onset of MGNE is acute, whereas the onset of VE is insidious; (3) the onset of MGNE is marked by confusion and delirium, which do not occur in VE; (4) VE is frequently associated with radiculopathy, which is absent in MGNE; and (5) VE is associated with more marked alterations in cerebrospinal fluid (high protein levels and pleocytosis). The early neurological manifestations of MGNE should prompt a search for systemic CMV infection, which may lead to earlier treatment.

AIDS-Related Opportunistic Infections↗

Melan-A/MART-1 antigen expression in cutaneous and ocular melanomas.

The human immune repertoire appears to be capable of recognizing normal antigens expressed by tumor cells. Among these antigens, those of differentiation, characterized by a restricted tissue expression, could be of clinical interest since they may represent a target for immunotherapeutic protocols. In this context we have evaluated, in benign and malignant lesions of the melanocytic lineage, the expression of the Melan-A/MART-1 antigen, which has been shown to be recognized by T cells, of HLA-A2 melanoma patients. The immunohistochemical analysis conducted with a Melan-A/MART-1 monoclonal antibody demonstrated that the antigen expression does not correlate with transformation or tumor progression. At variable levels Melan-A/MART-1, differently from other differentiation antigens, is homogeneously expressed by multiple autologous metastases and by melanoma metastases at different body sites. This tissue distribution adds further biological support to the ongoing use of Melan-A/MART-1-related peptides in active immunotherapy.

Antibodies, Monoclonal↗

Effects of HIV seropositivity and drug abuse on cognitive function.

Fifty-eight HIV-positive drug abusers and 22 HIV-positive nondrug abusers at stages II-III and IV of the Centers for Disease Control classification were evaluated neuropsychologically. The study confirmed previous findings that drug abuse has a negative influence on cognitive function. It also emerges that seropositivity affects cognitive function, although the poor performance of group II-III patients compared to group IV may be explained by factors related to seropositivity (anxiety and panic) rather than the disease itself. It is concluded that disease-related factors probably determine cognitive performance in the earlier stages of HIV infection.

AIDS Dementia Complex↗