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Biomedical subjects

G Ugolini

Publications and source records attributed to G Ugolini.

At least 19 recordsLinked to original sources
PubMed2000

Alzheimer-like neurodegeneration in aged antinerve growth factor transgenic mice.

Neurotrophin nerve growth factor (NGF) has been suggested to be involved in age-related neurodegenerative diseases, but no transgenic model is currently available to study this concept. We have obtained transgenic mice expressing a neutralizing anti-NGF recombinant antibody, in which the levels of antibodies are three orders of magnitude higher in adult than in newborn mice [F.R., S. C. , A.C., E. Di Daniel, J. Franzot, S. Gonfloni, G. Rossi, N. B. & A. C. (2000) J. Neurosci., 20, 2589-2601]. In this paper, we analyze the phenotype of aged anti-NGF transgenic mice and demonstrate that these mice acquire an age-dependent neurodegenerative pathology including amyloid plaques, insoluble and hyperphosphorylated tau, and neurofibrillary tangles in cortical and hippocampal neurons. Aged anti-NGF mice also display extensive neuronal loss throughout the cortex, cholinergic deficit in the basal forebrain, and behavioral deficits. The overall picture is strikingly reminiscent of human Alzheimer's disease. Aged anti-NGF mice represent, to our knowledge, the most comprehensive animal model for this severe neurodegenerative disease. Also, these results demonstrate that, in mice, a deficit in the signaling and/or transport of NGF leads to neurodegeneration.

Aging↗
PubMed2000

Targeted photodestruction of human colon cancer cells using charged 17.1A chlorin e6 immunoconjugates.

The goal of this study was to develop a strategy for the selective destruction of colorectal cancer cells. Towards this end, photoimmunoconjugates were prepared between the anti-colon cancer monoclonal antibody 17.1A and the photosensitizer (PS) chlorin(e6) (c(e6)). Polylysine linkers bearing several c(e6) molecules were covalently attached in a site-specific manner to partially reduced IgG molecules, which allowed photoimmunoconjugates to bear either cationic or anionic charges. The conjugates retained immunoreactivity as shown by enzyme-linked immunosorbent assays and by competition studies with native antibody. The overall charge on the photoimmunoconjugate was an important determinant of PS delivery. The cationic photoimmunoconjugate delivered 4 times more c(e6) to the cells than the anionic photoimmunoconjugate, and both 17.1A conjugates showed, in comparison to non-specific rabbit IgG conjugates, selectivity for antigen-positive target cells. Illumination with only 3 J cm(-2) of 666 nm light reduced the number of colony forming cells by more than 90% for the cationic 17.1A conjugate and by 73% for the anionic 17.1A conjugate after incubation with 1 microM c(e6) equivalent of the respective conjugates. By contrast, 1 microM free c(e6) gave only a 35% reduction in colonies. These data suggest photoimmunoconjugates may have applications in photoimmunotherapy where destruction of colorectal cancer cells is required.

Antibodies, Monoclonal↗
PubMed2000

Neuronal pathways for the propagation of herpes simplex virus type 1 from one retina to the other in a murine model.

Herpetic retinitis in humans is characterized by a high frequency of bilateral localization. In order to determine the possible mechanisms leading to bilateral retinitis, we studied the pathways by which herpes simplex virus type 1 (HSV-1) is propagated from one retina to the other after intravitreal injection in mice. HSV-1 strain SC16 (90 p.f.u.) was injected into the vitreous body of the left eye of BALB/c mice. Animals were sacrificed 1, 2, 3, 4 and 5 days post-inoculation (p.i.). Histological sections were studied by immunochemical staining. Primary retinitis in the inoculated eye (beginning 1 day p.i.) was followed by contralateral retinitis (in the uninoculated eye) starting at 3 days p.i. Infected neurons of central visual pathway nuclei (lateral geniculate nuclei, suprachiasmatic nuclei and pretectal areas) were detected at 4 days p.i. Iris and ciliary body infection was minimal early on, but became extensive thereafter and was accompanied by the infection of connected sympathetic and parasympathetic pathways. The pattern of virus propagation over time suggests that the onset of contralateral retinitis was mediated by local (non-synaptic) transfer in the optic chiasm from infected to uninfected axons of the optic nerves. Later, retinopetal transneuronal propagation of the virus from visual pathways may have contributed to increase the severity of contralateral retinitis.

Animals↗
PubMed1999

Spinal and brain circuits to motoneurons of the bulbospongiosus muscle: retrograde transneuronal tracing with rabies virus.

Retrograde transneuronal tracing with rabies virus from the left bulbospongiosus muscle (BS) was used to identify the neural circuits underlying its peripheral and central activation. Rats were killed at 2, 3, 4, and 5 days post-inoculation (p.i.). Rabies immunolabelling was combined with immunohistochemical detection of choline acetyltransferase and oxytocin. Virus uptake was restricted to ipsilateral BS motoneurons (2 days p.i.). The onset of transfer (3 days p.i.) visualized interneurons in the dorsal grey commissure (DGC), intermediate zone, and sacral parasympathetic nucleus (SPN), mainly in DGC at L5-S1, and revealed synaptic connections between BS and external urethral sphincter motoneurons. At 4 and 5 days p.i., higher-order interneurons were labelled in other spinal areas and segments. Supraspinal labelling initially involved only Barrington's nucleus, nucleus reticularis magnocellularis, and paragigantocellularis lateralis (4 days p.i.). Later, labelling extended to other populations traditionally associated with control of sexual activity and micturition (periaqueductal grey, paraventricular nucleus, medial preoptic area, prefrontal cortex), but also indicated the intervention of somatic descending motor pathways (vestibulospinal and reticulospinal neurons, "hindlimb" regions of sensorimotor cortex and red nucleus) and cerebellar nuclei in multisynaptic innervation of the labelled motoneurons. Dual color immunofluorescence disclosed multisynaptic links between these motoneurons and thoracolumbar medial sympathetic (choline acetyltransferase-immunoreactive) neurons. In contrast, preganglionic neurons in SPN and most oxytocinergic neurons in paraventricular hypothalamic nucleus remained unlabelled, suggesting that parasympathetic and somatic outflow to pelvic organs are probably controlled by separate interneuronal populations and that oxytocinergic spinal projections are more likely to influence sacral autonomic rather than somatic outflow.

Animals↗
PubMed1998

Does lunar position influence the time of delivery? A statistical analysis.

OBJECTIVE: To study the relationship between lunar position and the day of delivery; to investigate the synodic distribution of spontaneous deliveries, especially in relation to the presence of a full moon. STUDY DESIGN: Retrospective analysis of 1248 spontaneous full-term deliveries in three-year period (36 lunar months), setted at Department of Obstetrics and Gynaecology, Civil Hospital, Fano (Marche, Italy), using circular statistics techniques. RESULTS: A connection between the distribution of spontaneous full-term deliveries and the lunar month was found. The effect of the phases of the moon seems to be particularly relevant in multiparae and plurigravidae; in these cases, the mean day of delivery corresponds to the first or second day after the full moon. CONCLUSIONS: In this paper the effect of lunar phases on the time of delivery is shown. This influence seems to be especially relevant in the case of multiparae and plurigravidae. Nevertheless, it is too weak to allow for prediction regarding the days with the highest frequency of deliveries.

Confidence Intervals↗
PubMed1998

Nitric oxide sensitive depolarization-induced hyperpolarization: a possible role for gap junctions during development.

Electrical coupling is a widespread feature of developing neuronal circuits and it contributes to the generation of patterned activity. In the developing rat hippocampus, release of GABA by coactive hilar interneurones generates widespread synchronized activity. Here it is shown that hilar interneurones strongly rectify in the outward direction when depolarized. This depolarization-induced hyperpolarization, abolished by gap junction uncouplers, is modulated by nitric oxide. This phenomenon might represent a current-shunting mechanism of the excess current by providing functional inhibition at a developmental stage when GABA is excitatory. Spatial buffering of the current might represent an osmotic mechanism for growth and differentiation.

Anesthetics, Inhalation↗
PubMed1998

Some unexpected results in time distribution analysis of spontaneous deliveries.

OBJECTIVE: To study time distribution of spontaneous deliveries. METHODS: A retrospective analysis of 1,791 spontaneous deliveries over a 4-year period (1993-1996) was made at the department of Obstetrics and Gynaecology, Civil Hospital, Fano, Italy. Circular statistics techniques (maximization of mean vector length) were used. RESULTS: Some unexpected infradian disuniformities (with 60- and 90-hour periods) were observed. Moreover, a correlation between the distribution of spontaneous deliveries and the lunar phases was found. CONCLUSIONS: In this study, some unexpected infradian disuniformities were found. However, no biological explanations appear to be reasonable in light of current knowledge, so the interpretation of these results remains an open question.

Delivery, Obstetric↗
PubMed1997

Co-localization of truncated tau and DNA fragmentation in Alzheimer's disease neurones.

Monoclonal antibody MN423 stains all hallmarks of tau neurofibrillary pathology in Alzheimer's disease (AD), without reacting with full-length tau. It recognizes tau molecules which are cleaved at Glu-391, suggesting that tau is endogenously truncated in AD brains. We investigated whether truncation of tau takes place in pre-tangle neurones. Our results showed that tau truncation occurs inside AD neurones in the absence of other signs of AD neurofibrillary pathology. Using in situ end labelling (ISEL) of DNA we found evidence for DNA fragmentation in a significant subpopulation of MN423-positive neurones. Our results therefore suggest that tau truncation is an early intracellular event preceding cell death in AD.

Aged↗
PubMed1997

A pacemaker current in dye-coupled hilar interneurons contributes to the generation of giant GABAergic potentials in developing hippocampus.

The establishment of synaptic connections and their refinement during development require neural activity. Increasing evidence suggests that spontaneous bursts of neural activity within an immature network are mediated by gamma-aminobutyric acid via a paradoxical excitatory action. Our data show that in the developing hippocampus such synchronous burst activity is generated in the hilar region by transiently coupled cells. These cells have been identified as neuronal elements because they fire action potentials and they are not positive for the glial fibrillary acidic protein staining. Oscillations in hilar cells are "paced" by a hyperpolarization-activated current, with properties of Ih. Coactivated interneurons synchronously release GABA, which via its excitatory action may serve a neurotrophic function during the refinement of hippocampal circuitry.

Aging↗
PubMed1997

Evaluation of factors influencing 5-fluorouracil-induced diarrhea in colorectal cancer patients. An Italian Group for the Study of Digestive Tract Cancer (GISCAD) study.

Diarrhea is one of the dose-limiting toxicities for administration of fluorouracil (5FU) in patients with colorectal cancer and can result in severe morbidity and mortality. No well-defined prognostic factors influencing 5FU-associated diarrhea have been identified, which means its occurrence is unforeseeable. The aim of this study was to check whether any characteristics related to patients or chemotherapy could allow the identification of subsets of patients at higher risk of developing diarrhea while receiving a regimen containing 5FU. A logistic regression analysis was performed with age, sex, site of primary tumor, presence of primary tumor, presence of colostomy, time since surgery, number of courses of chemotherapy, diarrhea in previous courses, season of treatment, and chemotherapeutic regimens used as model parameters to predict occurrence of diarrhea in 258 colorectal cancer patients receiving a 5FU-containing regimen. Presence of primary tumor (P = 0.004), previous episodes of chemotherapy-related diarrhea (P = 0.00005) and summer season (P = 0.014) were found to be significant risk factors for developing diarrhea. The other variables examined, such as age, sex, chemotherapeutic regimen, site of primary tumor, presence of colostomy, and time since surgery, were not significantly correlated to diarrhea. Chemotherapeutic regimen was the only parameter that allowed prediction of the severity of diarrhea: 5FU/6S-leucovorin/interferon caused more severe diarrhea, followed by 5FU/leucovorin weekly. Although the analysis of these clinical features does not seem to allow the definition of a well-defined subset of colorectal cancer patients at higher risk of 5FU-induced diarrhea, it can be recommended that patients with primary tumor, or who have experienced diarrhea in earlier courses of chemotherapy or are receiving treatment in summer should be carefully monitored, especially in the first cycles.

Adult↗
PubMed1997

[Incidence of lunar position in the distribution of deliveries. A statistical analysis].

OBJECTIVE: To point out the influence of the lunar position on the distribution of deliveries. METHODS: We examined all the full-term spontaneous deliveries that occurred at the Civil Hospital in Fano (March) throughout 24 synodic months in a 2-year period (1993-1994). In order to perform the statistical analysis, each delivery was considered as a single measure. We used techniques of circular statistics to execute data analysis. RESULTS: A significant relationship between lunar position and distribution of deliveries was pointed out in multigravidae (in detail, the deliveries resulted clustered around the full moon phase). On the contrary, no significant relation was observed in primigravidae. CONCLUSIONS: The observed results evidence a significant influence of the position of the moon on the distribution of deliveries, especially in multigravidae.

Delivery, Obstetric↗
PubMed1996

Deletion of glycoprotein gE reduces the propagation of pseudorabies virus in the nervous system of mice after intranasal inoculation.

A pseudorabies virus (PrV) mutant, deficient in the nonessential glycoprotein E (gE) and expressing the LacZ gene (gE- beta gal+ PrV), and its rescued virus were inoculated intranasally in mice. The median lethal dose of gE- beta gal+ PrV was similar to that of the parental Kaplan strain, but mice survived longer and did not develop symptoms of pseudorabies. In the nasal mucosa, gE- beta gal+ PrV replicated less efficiently than rescued virus. gE- beta gal+ PrV could infect first-order trigeminal and sympathetic neurons innervating the nasal mucosa. However, transneuronal transfer to second-order cells groups did not occur in trigeminal pathways and was severely reduced in sympathetic pathways. The mutant was also unable to propagate in the parasympathetic system. In contrast, gE-rescued virus was transferred transneuronally in trigeminal, sympathetic, and parasympathetic pathways, like wild-type PrV. These findings provide further evidence that deletion of gE specifically affects transneuronal transfer of PrV more than penetration and multiplication of the virus in first-order neurons.

Administration, Intranasal↗
PubMed1996

Esthetic double-structure fixed partial dentures.

A new technical procedure for fixed partial dentures and single inlays allows the use of a metal supporting structure with independent ceramic coverage. The advantages of the technique are the bonding of metal to beveled dentinal margins with conventional cement and the acid-etched resin composite cementation of the ceramic, which permits more conservative preparation of the teeth. The complexity of the structure, the laboratory costs, and the doubling of the cementation procedures are the main disadvantages of the technique.

Cementation↗
PubMed1996

[Transanal ultrasonography in the study of fistulas of perianal abscess].

The fistulous tracks and abscesses may be related anatomically to the anal sphincters and levator ani muscles. Defining the anatomical relationship between the fistulous lesion and the anal sphincters and/or adjacent organs is essential for correct management. Clinical examination can suggest possible sepsis or the direction of the fistulous track. We report the results of anal endosonography in the evaluation of 54 patients affected by perianal sepsis and fistula in ano. Anal endosonography has correctly identified 22 of 22 internal openings seen at the surgery, 14 of 16 intersphincteric tracts while only 7 of the 9 trans-sphincteric tracks described by anal endosonography were present at the surgery. All the abscesses were correctly identified. Anal endosonography provides a high-resolution image of the anatomy of anal canal and defines the anatomy of tracks and abscesses in relation to the sphincters, determines if there has been trans-sphincteric extension of the sepsis and assesses the state of the sphincters. We have observed a good correlation between the preoperative AES findings and those at surgery. We conclude that anal endosonography is a useful diagnostic procedure in patients with perianal sepsis.

Abscess↗
PubMed1995

TrkA, TrkB and p75 mRNA expression is developmentally regulated in the rat retina.

We examined the cellular distribution of mRNAs coding for the neurotrophin receptors TrkA, TrkB and p75 in the rat retina during early postnatal development. At P0 (postnatal day 0), mRNAs coding for each of the three receptors were detected in the ganglion cell layer (GCL) and in the inner plexiform layer (IPL), the latter structure essentially containing retinal ganglion cell processes at this developmental stage. At P5, the innermost part of the inner nuclear layer (INL) also expressed TrkA, TrkB and p75 mRNAs. Finally, the GCL, IPL and the whole INL of P10 retinae were labeled by the three probes. The developmentally regulated expression of these receptors underlies a possible role for neurotrophins in the differentiation and survival of retinal cells.

Animals↗
PubMed1995

Specificity of rabies virus as a transneuronal tracer of motor networks: transfer from hypoglossal motoneurons to connected second-order and higher order central nervous system cell groups.

The specificity of transneuronal transfer of rabies virus [challenge virus standard (CVS) strain] was evaluated in a well-characterized neuronal network, i.e., retrograde infection of hypoglossal motoneurons and transneuronal transfer to connected (second-order) brainstem neurons. The distribution of the virus in the central nervous system was studied immunohistochemically at sequential intervals after unilateral inoculation into the hypoglossal nerve. The extent of transneuronal transfer of rabies virus was strictly time dependent and was distinguished in five stages. At 1 day postinoculation, labelling involved only hypoglossal motoneurons (stage 1). Retrograde transneuronal transfer occurred from 2.0-2.5 days postinoculation (stage 2). In stages 2-4, different groups of second-order neurons were labelled sequentially, depending on the strength of their input to the hypoglossal nucleus. In stages 4 and 5, labelling extended to several cortical and subcortical cell groups, which can be regarded as higher order because they are known to control tongue movements and/or to provide input to hypoglossal-projecting cell groups. The pattern of transneuronal transfer of rabies virus resembles that of alpha-herpesviruses with regard to the nonsynchronous labelling of different groups of second-order neurons and the transfer to higher order neurons. In striking contrast to alpha-herpesviruses, the transneuronal transfer of rabies is not accompanied by neuronal degeneration. Moreover, local spread of rabies from infected neurons and axons to adjoining glial cells, neurons, or fibers of passage does not occur. The results show that rabies virus is a very efficient transneuronal tracer. Results also provide a new insight into the organization of cortical and subcortical higher order neurons that mediate descending control of tongue movements indirectly via hypoglossal-projecting neurons.

Animals↗
PubMed1995

Transanal local resection for benign and malignant rectal tumours.

Local therapy has been widely reported and accepted for benign tumours and carefully selected cancers of the rectum. Thirty-three patients with benign or malignant low rectal tumors have undergone a prospective evaluation after local resection with transanal electroresection as described by Faivre. Patients were divided in three groups: 1) local excision of benign tumours (12 patients), 2) curative resection for localised malignant tumours (7 patients) and 3) palliative local resection for malignant tumours (14 patients). The complications included transient incontinence and rectal bleeding. Patients have been followed for a mean period of 18 months (1-54). In group 3 there were four (28%) recurrences. The remainder of the patients with malignant tumours have been free of disease on follow-up. Although it is ideal for benign neoplasms, further follow-up is needed to determine its true indication in malignant lesions.

Adult↗