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Biomedical subjects

G Ugolini

Publications and source records attributed to G Ugolini.

At least 19 recordsLinked to original sources

Fitz-Hugh-Curtis-syndrome mimicking acute cholecystitis: value of new ultrasound findings in the differential diagnosis.

Fitz-Hugh-Curtis is a rare syndrome characterised by perihepatitis following pelvic inflammatory disease. We report the case of a patient with a right ovarian teratoma, abnormal liver tests and pain in the right abdomen and shoulder, initially attributed to an acalculous cholecystitis. Before gynaecological surgery, a repeat ultrasound scan found several small avascular peritoneal masses at the upper dome of the liver, not reported in the initial examination. This prompted laparoscopic exploration of the subdiaphragmatic space, and the final diagnosis of Fitz-Hugh-Curtis-syndrome was made. Such ultrasound finding appears to be a new diagnostic feature of this syndrome.

Adult↗

Oculomotor areas of the primate frontal lobes: a transneuronal transfer of rabies virus and [14C]-2-deoxyglucose functional imaging study.

We used the [14C]-2-deoxyglucose method to study the location and extent of primate frontal lobe areas activated for saccades and fixation and the retrograde transneuronal transfer of rabies virus to determine whether these regions are oligosynaptically connected with extraocular motoneurons. Fixation-related increases of local cerebral glucose utilization (LCGU) values were found around the fundus of the inferior limb of the arcuate sulcus (AS) just ventral to its genu, in the dorsomedial frontal cortex (DMFC), cingulate cortex, and orbitofrontal cortex. Significant increases of LCGU values were found in and around both banks of the AS, DMFC, and caudal principal, cingulate, and orbitofrontal cortices of monkeys executing visually guided saccades. All of these areas are oligosynaptically connected to extraocular motoneurons, as shown by the presence of retrogradely transneuronally labeled cells after injection of rabies virus in the lateral rectus muscle. Our data demonstrate that the arcuate oculomotor cortex occupies a region considerably larger than the classic, electrical stimulation-defined, frontal eye field. Besides a large part of the anterior bank of the AS, it includes the caudal prearcuate convexity and part of the premotor cortex in the posterior bank of the AS. They also demonstrate that the oculomotor DMFC occupies a small area straddling the ridge of the brain medial to the superior ramus of the AS. Our results support the notion that a network of several interconnected frontal lobe regions is activated during rapid, visually guided eye movements and that their output is conveyed in parallel to subcortical structures projecting to extraocular motoneurons.

Animals↗

[Treatment of complicated peptic ulcer: personal experience].

BACKGROUND: The availability of drugs which can effectively inhibit gastric secretion allowed the control of the peptic disease in almost all the patients, but the incidence of complications is substantially unchanged. METHODS: In the present study, we performed a retrospective evaluation of 153 patients treated for complicated peptic ulcer (hemorrhage and perforation) in the last 6 years. Hemor-rhage is a common onset of the peptic disease and it rarely requires a surgical treatment, because medical and endoscopic therapies are successful in a high number of patients. RESULTS: Surgery was necessary in 17.2% of the cases in the group of patients studied. CONCLUSIONS: Our experience confirms the high operative mortality in the patients who underwent surgery for hemorrhage related to complicated peptic ulcer because of the frequent presence of several risk factors. Surgical therapy is the main procedure of treatment of perforated peptic ulcer and in the group of patient examined all the cases of perforation underwent surgical operation. In conclusion, despite the progress of pharmacological and endoscopic therapies, surgical treatment is the best therapy of complicated peptic ulcer.

Adult↗

Modern concepts of brainstem anatomy: from extraocular motoneurons to proprioceptive pathways.

The extraocular muscles, unlike the skeletal muscles, contain non-twitch muscle fibers. Recent experiments have located the non-twitch motoneurons. They lie around the periphery of the oculomotor, trochlear and abducens nuclei, separate from the more usual twitch motoneurons that cluster within the boundaries of the classical motor nuclei. The premotor inputs to non-twitch neurons were traced by the injection of rabies virus into the distal tip of the lateral rectus muscle. Retrogradely labeled cells were found in areas associated with the neural integrator, vergence and smooth pursuit premotor areas, but not the saccadic premotor burst neurons or the direct vestibulo-ocular pathways. The rabies tracing emphasizes for the first time that the central mesencephalic reticular formation (cMRF) and the supraoculomotor area exert direct premotor control over the non-twitch motoneurons. Because the two sets of motoneurons do not receive the same afferents, they must have different functions; these are not yet clarified. These results are not compatible with the concept of a single final common pathway from motoneurons to eye muscles. Putative sensory receptors, palisade endings, are located at the tips of non-twitch muscle fibers reminiscent of an inverted muscle spindle, which would make the non-twitch motoneurons, gamma-motoneurons. We propose that twitch motoneurons are the major source of tension used for eye movements, whereas non-twitch motoneurons are more important for fine alignment of the eyes. Furthermore, the non-twitch motoneurons could be controlled through sensory feedback networks (including perhaps proprioceptive signals from the palisade endings) that are relayed through the superior colliculus and via cMRF to the non-twitch motoneurons. The clinical repercussions of these hypotheses are discussed.

Animals↗

Expression profile of epidermal differentiation complex genes in normal and anal cancer cells.

Anal cancer originates from a peculiar histological region and provides a useful model for investigating alterations in proliferation and/or differentiation of neoplastic keratinocytes. Epidermal differentiation complex (EDC) genes, which form one of the major gene clusters in the human genome, are involved in the terminal differentiation of epithelial cells and in many instances have been implicated in epithelial tumours. We constructed a DNA macroarray capable of characterising the expression profiles of the entire EDC gene complex in normal mucosa and anal cancer biopsies of seven unrelated patients. Brain tissue and cultured keratinocytes were used as controls. All anal cancer samples showed expression profiles in which none of the EDC genes was silent, as evaluated by phosphor-imager analysis. Variance analysis showed significantly lower expression of SPRR2 with respect to SPRR1 or SPRR3, and significantly higher expression of S100A8 than of other S100A subfamily members. At hierarchical clustering analysis, the four basaloid anal cancer cases conglomerated in the top five positions. The macroarray method used by us provides the first demonstration of the expression profile of the EDC gene family in anal cancer, and is capable of producing significant information on the subgrouping of epithelial tumours such as anal cancer.

Adult↗

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↗

The neuronal microtubule-associated protein tau is a substrate for caspase-3 and an effector of apoptosis.

We have identified a class of tau fragments inducing apoptosis in different cellular contexts, including a human teratocarcinoma-derived cell line (NT2 cells) representing committed human neuronal precursors. We have found a transition point inside the tau molecule beyond which the fragments lose their ability to induce apoptosis. This transition point is located around one of the putative caspase-3 cleavage sites. This is the only site that can be effectively used by caspase-3 in vitro, releasing the C-terminal 19 amino acids of tau. These results establish tau as a substrate for an apoptotic protease that turns tau itself into an effector of apoptosis. Accordingly, tau may be involved in a self-propagating process like what has been predicted for the pathogenesis of different neurodegenerative disorders.

3T3 Cells↗

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↗

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↗

Expression analysis and mutational screening of the epithelium-specific ets gene-1 (ESE-1) in patients with squamous anal cancer.

To investigate whether ESE-1 gene abnormalities are involved in alterations of epithelial cell differentiation in squamous anal cancer ESE-1 expression and structure were screened in six patients by reverse transcriptase-polymerase chain reaction (RT-PCR) and automated sequence analysis. The complete cDNA of isoform ESE-1b was always expressed and correctly spliced, with single nucleotide polymorphism being observed in two cases. Presence of ESE-1b point mutations was excluded. Expression of SPRR2A and ENDOA/CK8, two epithelium-specific ESE-1 target genes, were revealed by RT-PCR in all cases. This first report of expression of ESE-1, and of SPRR2A and ENDOA/CK8 (both related to terminal differentiation in different types of epithelia lining) in anal cancer excludes the hypothesis that these genes influenced carcinogenesis in our patients. Despite selecting of patients without clinical evidence of HPV infection, PCR consistently revealed HPV-16 DNA, highlighting the importance of HPV infection in anal cancer.

Adult↗

Neuronal propagation of HSV1 from the oral mucosa to the eye.

PURPOSE: To identify possible neuronal pathways leading to herpetic ocular disease after primary oral infection in mice. METHODS: The SC16 strain of herpes simplex virus (HSV)-1 (10(6) plaque-forming units) was injected into the mucocutaneous border of the left upper lip. Animals were killed 2 to 10 days postinoculation (DPI). Spread of the virus in neural structures was studied by immunochemistry. RESULTS: HSV1 first replicated at the site of inoculation and then at the superior cervical ganglion (at 2 DPI). The trigeminal ganglion and the facial nerve fibers were infected by 4 DPI. Infection of the ciliary body and iris occurred at 6 DPI, together with several brain stem nuclei belonging to the autonomic or sensory pathways. Between 8 and 10 DPI, the neural infection gradually cleared up, except for the ipsilateral sympathetic ganglion, and ipsilateral keratitis appeared in some animals. CONCLUSIONS: The pattern of viral dissemination in this mouse model suggests that infection of iris and ciliary body results from transfer of virus in the superior cervical ganglion from sympathetic neurons innervating the lip to neighboring neurons innervating the anterior uvea. Later, zosteriform spread of virus from the trigeminal system may have contributed to the clinical and histologic findings.

Animals↗

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↗

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↗

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↗

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↗

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↗

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↗