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Biomedical subjects

S Russo

Publications and source records attributed to S Russo.

At least 19 recordsLinked to original sources
PubMed1999

Activation of CD40 favors the growth and vascularization of Kaposi's sarcoma.

Although CD40 is expressed by several tumor lines and is up-regulated in tumor vascular endothelium, its role in tumor biology is still unclear. In the present study, we investigated the role of CD40 in the growth and vascularization of Kaposi's sarcoma (KS). In vitro, stimulation of CD40 induced migration of KS cells and inhibited vincristine-induced apoptosis. Similarly, the CD40 engagement on endothelial cells resulted in cell contraction, migration, and prevention of serum withdrawal-apoptosis. To understand the biological relevance of CD40 in vivo, KS cells were engineered to express and release a soluble form of CD40 (KS-sCD40) able to disrupt CD40-CD154 interaction. SCID mice s.c. injected with KS-sCD40 cells developed tumors that were significantly smaller than those induced by control cells (KS-neo). In addition, KS-sCD40 tumors showed several areas of necrosis, diffuse presence of apoptotic cells, and poor vascularization. In contrast, KS-neo tumors showed few or absent areas of necrosis and apoptosis and intense vascularization. Moreover, anti-CD40 Abs stimulated neo-angiogenesis in a murine model in which s.c. implantation of Matrigel was used as a vehicle for the delivery of mediators. These observations provide demonstration that CD40 supports tumor cell survival, growth, and neo-vascularization of KS.

Animals↗
PubMed1999

[An unusual episode of angina].

The authors report the case of a 77-year-old woman suffering from ischemic cardiopathy, arterial hypertension and NID diabetes mellitus who was hospitalised for diabetic retinopathy. Following the topical administration of a drop of phenylephrine in the right eye, in preparation for fluoroangiography, she suffered an attack of angina pectoris. This event was clearly identified by a ECG carried out at the time which highlighted the sublevelling of the ST tract in the precordial derivations V2-V5, and by ecocardiographic imaging that showed septo-apical, anterior-apical and anterior-median transient segmentary hypokinesia. This case underlines the need for prudence and emphasises the need to regard patients suffering from ischemic cardiopathy as high-risk when undergoing diagnostic tests, in particular if these involve the use of vasoactive drugs.

Aged↗
PubMed1999

BHV-1: new molecular approaches to control a common and widespread infection.

BACKGROUND: Herpesviruses are widespread viruses, causing severe infections in both humans and animals. Eradication of herpesviruses is extremely difficult because of their ability to establish latent and life-long infections. However, latency is only one tool that has evolved in herpesviruses to successfully infect their hosts; such viruses display a wide (and still incompletely known) panoply of genes and proteins that are able to counteract immune responses of their hosts. Envelope glycoproteins and cytokine inhibitors are two examples of such weapons. All of these factors make it difficult to develop diagnostics and vaccines, unless they are based on molecular techniques. MATERIALS AND METHODS: Animal herpesviruses, because of their striking similarity to human ones, are suitable models to study the molecular biology of herpesviruses and develop strategies aimed at designing neurotropic live vectors for gene therapy as well as engineered attenuated vaccines. RESULTS: BHV-1 is a neurotropic herpesvirus causing infectious rhinotracheitis (IBR) in cattle. It is a major plague in zootechnics and commercial trade, because of its ability to spread through asymptomatic carrier animals, frozen semen, and embryos. Such portals of infections are also important for human herpesviruses, which mainly cause systemic, eye, and genital tract infections, leading even to the development of cancer. CONCLUSIONS: This review covers both the genetics and molecular biology of BHV-1 and its related herpesviruses. Epidemiology and diagnostic approaches to herpesvirus infections are presented. The role of herpesviruses in gene therapy and a broad introduction to classic and engineered vaccines against herpesviruses are also provided. http://link.springer-ny. com/link/service/journals/00020/bibs/5n5p261.html

Animals↗
PubMed1998

Expression of bovine leukemia virus ENV glycoprotein in insect cells by recombinant baculovirus.

The gp51-p30 glycoprotein constituting BLV envelope was expressed in Sf-21 insect cells by means of recombinant baculoviruses. Post-infection cell lysates were analyzed, in order to define the immunologic reactivity of recombinant products. Oligosaccharide chains, containing N-acetylglucosamine, mannose, galactose and sialic acid were found on recombinant gp51-p30. In order to investigate the timing of transcription and translation of the glycoprotein, kinetic assays were carried out on cell lysates and directly in situ on Sf-21 cells during the course of baculovirus infection. The use of different solubilizing reagents was also evaluated in order to rescue recombinant glycoprotein from its subcellular location.

Animals↗
PubMed1998

Molecular characterization of FRAXE-positive subjects with mental impairement in two unrelated Italian families.

The FRAXE fragile site, 600 Kb distal to the more common FRAXA, has been reported to be expressed in subjects with mild nonsyndromal mental retardation. Amplification of more than 200 GCC repeats associated with methylation of the adjacent CpG island at Xq28 is responsible for FRAXE fragility. We describe two unrelated, mentally retarded males identified during a screening for fragile X syndrome. Both index cases underwent FRAXE molecular analysis, following cytogenetic expression of the fra X site and negative FRAXA test. In family 1, we were able to investigate other 13 subjects over three generations, identifying two additional FRAXE-positive males, one with a fully mutated allele and one with a mosaic genotype. Detailed evaluation of physical traits and psychometric tests was performed on three retarded males from family 1 and the propositus from family 2. All of them were found to lack a definite phenotype, and showed different degrees of mental retardation. Slight mental retardation was evident in the mosaic male, suggesting that methylation might be an important determinant of mental impairment.

Adolescent↗
PubMed1998

Congenital megalourethra associated with urethral duplication and imperforate anus.

A newborn with a prenatal diagnosis of right hydroureteronephrosis and enlarged penis is presented. At birth, the baby had an imperforate anus (IA) with a megalourethra; radiologic and ultrasonographic studies showed a left polycystic kidney and right hydroureteronephrosis, right vesicoureteral reflux, and an incomplete urethral duplication with dilatation of the posterior urethra. The IA was corrected on the 1st day of life and a vesicostomy was performed at 1 month. At 1 year of age the valve obstructing the ventral posterior urethra was resected and the vesicostomy was closed. At 14 months the baby underwent a urethroplasty with a vertical preputial tubularized island flap and excision of the penile urethral duplication. Exact knowledge of the malformation was essential in planning the appropriate surgical treatment.

Anus, Imperforate↗
PubMed1998

A point mutation in the glutamate binding site blocks desensitization of AMPA receptors.

Desensitization of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) receptors is thought to shape the synaptic response and act as a neuroprotective mechanism at central synapses, but the molecular mechanism underlying desensitization is poorly understood. We found that replacing the glutamate binding domain S1 of GluR3 (an AMPA receptor) with S1 of GluR6 (a kainate receptor) resulted in a fully active but completely nondesensitizing receptor. Smaller substitutions within S1 identified, besides two additional modulatory regions, a single exchange, L507Y, as is required and sufficient for the block of desensitization. This phenotype was specific for AMPA receptors and required an aromatic residue at this position. L507 lies between two residues (T504 and R509) that form part of the glutamate binding site. The physical proximity of these residues, which are involved in binding and gating, suggests they may form part of the link between these two events.

Binding Sites↗
PubMed1998

An unusual fragile X sibship: female compound heterozygote and male with a partially methylated full mutation.

We describe here a fragile X sibship of borderline retarded sister and brother born to carrier parents. The sister is a compound heterozygote (with a full mutation on one X chromosome and a pre-mutation on the other X chromosome). The brother has a partially methylated full mutation. The activation ratio (AR) for the sister's pre-mutation was 0.69 and the percent lack of methylation for the brother's full mutation was 73%. Intellectual and neuropsychological Wechsler Adult Intelligence Scale (W.A.I.S.) achievement tests reported full scale IQ scores of 74 in the sister and 77 in the brother. A significant discrepancy between verbal and performance IQ was found in the sister, indicating that her main impairment was in the cognitive area. The parents of this unusual sibship came from a small village, as did one of the two previously described cases of compound heterozygous females. These rare females raise special issues for genetic counselling in fragile X carrier couples, the frequency of which remains to be defined in different populations.

Chromosome Fragility↗
PubMed1998

Isolation and characterization of the fungal metabolite 3-O-methylviridicatin as an inhibitor of tumour necrosis factor alpha-induced human immunodeficiency virus replication.

The cytokine tumour necrosis factor alpha (TNF-alpha) has been shown to play a role in human immunodeficiency virus (HIV) replication by activating transcription of the provirus in both T cells and macrophages. Therefore, agents that block TNF-alpha-induced HIV expression could have therapeutic value in the treatment of AIDS. We have sought to identify antiviral agents that block TNF-alpha induction of HIV LTR-directed transcription, using a cell-based, virus-free assay system in automated high-throughput screening. HeLa cells were transfected with an HIV LTR-luciferase reporter plasmid and a stable line was isolated in which TNF-alpha increased luciferase production by two- to threefold. This cell line was used to screen approximately 15,000 fungal extracts. An inhibitory activity specific for TNF-alpha-induced HIV LTR transcription was observed in culture OS-F67406. The active component was isolated and identified as a known metabolite, 3-O-methylviridicatin, by NMR and mass spectrometry. No biological activity has been associated with this compound previously. This compound blocks TNF-alpha activation of the HIV LTR in the HeLa-based system, with an IC50 of 5 microM, and inhibited virus production in the OM-10.1 cell line, a model of chronic infection responsive to induction by TNF-alpha, with an IC50 of 2.5 microM.

Anti-HIV Agents↗
PubMed1998

Myogenic conversion of NIH3T3 cells by exogenous MyoD family members: dissociation of terminal differentiation from myotube formation.

Myogenic regulatory factors (MRF) of the MyoD family regulate the skeletal muscle differentiation program. Non-muscle cells transfected with exogenous MRF either are converted to the myogenic lineage or fail to express the muscle phenotype, depending on the cell type analysed. We report here that MRF-induced myogenic conversion of NIH3T3 cells results in an incomplete reprogramming of these cells. Transfected cells withdrew from the cell cycle and underwent biochemical differentiation but, surprisingly, terminally differentiated myocytes absolutely failed to fuse into multinucleated myotubes. Analysis of muscle regulatory and structural gene expression failed to provide an explanation for the fusion defectiveness. However, myogenic derivatives of NIH3T3 cells were shown to be unable to accumulate the transcripts encoding muscle-specific isoforms of the integrin subunit beta1D and the transcription factor MEF2D1b2, that depend on muscle-specific alternative splicing. Our results suggest that the fusion into myotubes is under a distinct genetic control that might depend, at least partially, on differential splicing.

3T3 Cells↗
PubMed1998

[Cervical lymphangioma in the adult: a report of a significant case].

UNLABELLED: Lymphangioma in the adult is quite rare: the most common localization in the head and neck region is at the posterior triangle of the cervical lateral region (75%). Moreover, it favors the right latero-cervical area (72%) thus supporting a disembryogenetic pathogenesis. Indeed, according to Dowd and Goetsch, the lymphatic tissues are rearranged in this area, creating the principle head and neck drainage. The presence of disembryogenetic alterations in the lymphatic architecture could go on unnoticed until the lymphatic circulation equilibrium is altered by some anatomo-functional event compromising the involved area. CLINICAL CASE: G.P., a 41-year-old male, presented a swelling in the right submandibular region since approximately 4 months and which had increased in size over the last 30 days. The case history revealed that, at the age of 18 he had been admitted to the hospital for surgical removal of an angiomatose phlegmonous neoformation while, at the age of 18 38, he had undergone surgery for a lipoma in the right temporo-zigomatic area. Head and neck CT using a contrast medium revealed a formation of mixed density, predominantly liquid, apparently multiloculated. The patient underwent surgery, via a right submandibular cervicotomy approach, to remove the cystic neoformation and attached submandibular gland. In addition, the plurilobate mass showed submentonier, parapharyngeal, subdigastric and subhyoid extensions. Histology led to a diagnosis of "cystic lymphangioma". The clinical case reported is quite unusual in that:--the submandibular (anterior triangle) location is rare, accounting for only 6.25% of the cervical manifestations;--the previous case history of this patient underlines the importance of an embryogenic alteration in the regional lymph network;--this condition, clinically manifest in infancy as a submandibular (angiomatose) phlegmon became latent in adulthood after surgery for right temporo-zigomatic lipoma. In light of the above data, it can be hypothesized that a disembryogenetic origin of the adult lymphangioma, associated with a predisposition (scarred areas further compromising the lymph vessel architecture) and some precipitating event (surgical trauma in adulthood), have lead to delayed development of the amartoma.

Adult↗
PubMed1998

[Nasal reactivity in systemic lupus erythematosus].

The present study was prompted by the fact that alterations in nasal respiration were observed in patients with active Systemic Lupus Erythematosus (SLE). These alterations were most likely of a disreactive nature and, thus, could not be attributed to pathology-induced vasculitic alterations. The study was performed using the case/control method. Patients with active SLE were selected on the basis of reference symptoms (difficulty in nasal breathing) and the absence of any significant alteration in the rhinological objectives. Basal, positioning and evoked (cold water, 5 degrees C) rhinomanometry was performed in line with the standards suggested by the "Committee Report on Standardization of Rhinomanometry". Positional testing of the SLE patients revealed "paradoxical response" (66% in the supine decubitus, 50% homolateral and 56% controlateral). In addition there was a statistically significant (p < 0.05) increase in resistance vs. the control group both in the positional testing and upon cold water stimulation. The authors recognized that the rhinomanometric values found in the SLE patients--index of nasal mucosa disreactivity--confirm the presence of the distonic-vegetative alterations characteristic of aspecific vasomotor rhinopathy. In conclusion, the authors hypothesize on the pathogenic mechanisms behind the clinical and instrumental conditions revealed in light of the documented autonomic neuropathy present in SLE patients.

Adult↗
PubMed1997

Transcriptional down-regulation of myogenin expression is associated with v-ras-induced block of differentiation in unestablished quail muscle cells.

Unestablished quail myoblasts were infected with a retroviral vector encoding the oncogenic form of H-Ras in order to investigate the mechanism by which this oncoprotein interferes with terminal differentiation. Primary quail myogenic cells exhibit the simultaneous expression of the muscle regulatory genes myf-5, MyoD and myogenin in proliferative conditions. v-ras-transformed myoblasts displayed an altered growth control and lost the competence for terminal differentiation. When expression of myogenic regulatory genes was analysed, it was immediately apparent that the difference between normal and v-ras-transformed cells was limited to a severely decreased level of myogenin expression. Forced expression of exogenous myogenin in v-ras-transformed quail myoblasts led to a striking recovery of the competence for terminal differentiation. The present data show that: (i) repression of myogenin expression is linked to the differentiation defective phenotype of quail myoblasts transformed by v-ras as well as other retroviral oncogenes; (ii) correction of the differentiation-defective phenotype of v-ras-transformed myoblasts by exogenous myogenin entailed reactivation of endogenous myogenin and of the E-box-dependent transactivating function. These results strongly indicate that myogenin expression plays a central role in regulating the transition into the terminally differentiated state and that its transcriptional down-regulation represents a nodal step in v-ras-induced block of differentiation.

Alpharetrovirus↗
PubMed1997

Enteric cryptosporidiosis in pediatric HIV infection.

BACKGROUND: Enteric cryptosporidiosis is a frequent problem in adults with human immunodeficiency virus (HIV) infection, but little is known of its features in children. The aim of this study was to investigate the incidence and the clinical features of cryptosporidiosis in HIV-infected children. METHODS: Thirty-five children with symptomatic HIV infection were screened every 2 months, and in case of diarrhea, for the presence of Cryptosporidium. Intestinal function tests were performed, and the fecal osmotic gap was measured in children with cryptosporidiosis. RESULTS: Seventy episodes of diarrhea occurred in 16 children in a median period of 17 months. Cryptosporidium was detected in five cases, all with full-blown acquired immunodeficiency syndrome. Cryptosporidiosis was significantly more protracted than any other form of diarrhea and was associated with dehydration and severe weight loss. Intestinal function was not modified during cryptosporidiosis. Osmotic gap values were consistent with secretory rather than osmotic diarrhea. In four cases, recovery was observed without specific treatment. CONCLUSIONS: Enteric cryptosporidiosis is a severe problem in advanced stages of HIV infection. It does not induce intestinal malabsorption. It induces diarrhea of secretory type. Recovery may be observed independently of therapy.

Animals↗
PubMed1997

[Local administration of somatostatin in joint diseases in athletes].

Somatostatin is a hormone produced by the hypothalamus, and is widely diffused outside the CNS. It inhibits the secretion of many glands. Recently it has been shown that somatostatin has been proposed in the treatment of phlogistic diseases of the joints by intra-articular administration. The authors show the results of a study conducted in 16 patients (athletes) with arthrosynovitis or tendinitis of the knee or of the ankle, in which somatostatin was administered (250 mg/treatment, 1 treatment/week). Somatostatin significantly reduced pain, improved movement function and decreased the effects of pain on daily activities. The treatment was very well tolerated locally and generally. In conclusion, somatostatin may be considered useful in the treatment of articular and tendineous phlogistic diseases, almost in athletes.

Adolescent↗
PubMed1997

[Guidelines for the treatment of acute asthma. A critical retrospective analysis].

Acute asthma attacks are frequently observed in common medical practice. However a unified and scientifically proven directive which advises objectively on the best management strategy for patients with acute asthma attacks is still lacking. In the present review we have accurately assessed various important points addressed in the recent international guidelines for acute asthma. This work has enabled us to derive precise and documented suggestions of practical importance which may be useful to the physician for a correct and judicious approach to the management of those patients with acute asthma attacks.

Acute Disease↗