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Biomedical subjects

S Russo

Publications and source records attributed to S Russo.

At least 37 records · Page 2Linked to original sources
PubMed2000

Induction carboplatin/paclitaxel followed by concurrent carboplatin/paclitaxel and dose-escalating conformal thoracic radiation therapy in unresectable stage IIIA/B nonsmall cell lung carcinoma: a modified Phase I trial.

BACKGROUND: A modified Phase I trial was conducted evaluating the incorporation of 3-dimensional conformal radiation therapy (3DCRT) into a strategy of sequential and concurrent carboplatin/paclitaxel in Stage III, unresectable nonsmall cell lung carcinoma (NSCLC). In addition, dose escalation of thoracic conformal radiation therapy (TCRT) from 60 to 74 gray (Gy) was performed. Endpoints included response rate, toxicity, and survival. METHODS: Twenty-nine patients with unresectable Stage III NSCLC were included. Patients received 2 cycles of induction carboplatin (AUC 6) and paclitaxel (225 mg/m(2)/3 hours) every 21 days. On Day 43, concurrent TCRT and weekly (x6) carboplatin (AUC 2) and paclitaxel (45 mg/m(2)/3 hours) was initiated. The TCRT dose was escalated from 60 to 74 Gy in 4 cohorts. RESULTS: The response rate to induction carboplatin/paclitaxel was 52%. Three patients (10%) experienced disease progression during the induction phase. No dose-limiting toxicity was seen during the escalation of the TCRT dose from 60 to 74 Gy. The major toxicity was esophagitis, with 18% of patients developing Radiation Therapy Oncology Group Grade 3 esophagitis. The overall response rate was 70% (1 complete response and 18 partial responses). Survival rates at 1 and 2 years were 69% and 45%, with a median survival of 21 months. The 1-year progression free survival probability was 41% (95% confidence interval, 23-59%). CONCLUSIONS: Incorporation of 3DCRT with sequential and concurrent carboplatin/paclitaxel is feasible, and dose escalation of TCRT to 74 Gy is possible with acceptable toxicity. Overall response and survival rates are encouraging. Accrual is continuing in a Phase II fashion at 74 Gy with sequential and concurrent carboplatin/paclitaxel.

Adult↗
PubMed2000

The specificity of neurological signs in schizophrenia: a review.

This review examines the extent to which neurological signs are more prevalent in schizophrenia patients, compared to mood-disorder patients and healthy subjects, and whether there is a pattern in any of the differences that may be found. We included 17 studies and calculated the weighted mean prevalence of 30 neurological signs. The prevalence of most signs appears to be significantly different between schizophrenia patients and normal controls, but there are fewer differences between schizophrenia and mood-disorder patients. Several signs - poor stereognosis and rhythm tapping - are even more prevalent in mood-disorder patients than in schizophrenia patients. Only lack of extinction, dysdiadochokinesia, poor tandem walk, finger-thumb-opposition and articulation are significantly more prevalent in schizophrenia compared to mood-disorder patients. Impaired motor coordination seems most specific to schizophrenia. The discriminating power of motor sequencing still needs to be studied. So far, there is no evidence of a clearly interpretable pattern of neurological signs distinguishing schizophrenia patients from mood-disorder patients.

Bipolar Disorder↗
PubMed2000

Novel mutations of ubiquitin protein ligase 3A gene in Italian patients with Angelman syndrome.

Angelman syndrome is a neurobehavioral disorder caused by defects of imprinted gene(s) on chromosome 15q11-13. AS-specific DNA methylation is found in patients carrying 3-4 Mb deletions ( approximately 70%), paternal uniparental disomy (3-5%) or imprinting center mutations (2-9%), while normal methylation pattern with biparental inheritance characterizes the remaining approximately 20-25% AS patients (Stalker et al.,1998; Tsai et al.,1998). Mutations in the Ubiquitin protein ligase 3A gene (UBE3A) have been found in the latter group, but only preliminary figures are available on their frequencies. We selected a sample of 25 AS patients with a clinical diagnosis of AS and a normal methylation pattern in order to search for mutations of the UBE3A gene. Automated sequencing of exons 8, 9, 10, 11 and 12 performed on our 25 patients allowed us to identify three novel mutations: an 897insA in two unrelated familial cases, a 2544insA and an E167X in two sporadic cases. Mutation R482X previously reported in a sporadic patient was identified in a third familial case. Hum Mutat 15:387, 2000.

Adolescent↗
PubMed2000

PAF produced by human breast cancer cells promotes migration and proliferation of tumor cells and neo-angiogenesis.

Platelet-activating factor (PAF), a phospholipid mediator of inflammation, is present in breast cancer tissue and correlates with microvessel density. In the present study, we investigated the biological significance of PAF synthesized within breast cancer. In vitro, we observed the production of PAF by two estrogen-dependent (MCF7 and T-47D) and an estrogen-independent (MDA-MB231) breast cancer cell lines after stimulation with vascular endothelial growth factor, basic fibroblast growth factor, hepatocyte growth factor, tumor necrosis factor, thrombin but not with estrogen, progesterone, and oxytocin. The sensitivity to agonist stimulation and the amount of PAF synthesized as cell-associated or released varied in different cell lines, being higher in MDA-MB231 cells, which are known to be highly invasive. We further demonstrate, by reverse transcriptase-polymerase chain reaction and cytofluorimetry, that all of the breast cancer cells express the PAF receptor and respond to PAF stimulation in terms of proliferation. Moreover, in MDA-MB231 cells PAF elicited cell motility. In vivo, two structurally different PAF receptor antagonists WEB 2170 and CV 3988 significantly reduced the formation of new vessels in a tumor induced by subcutaneous implantation of MDA-MB231 cells into SCID mice. In conclusion, these results suggest that PAF, produced and released by breast cancer cells, can contribute to tumor development by enhancing cell motility and proliferation and by stimulating the angiogenic response.

Animals↗
PubMed2000

A Lost Realm in the Internal Domains of the Betic-Rif Orogen (Spain and Morocco): Evidence from Conglomerates and Consequences for Alpine Geodynamic Evolution.

The Malaguide-Ghomaride Complex is capped by Upper Oligocene-Aquitanian clastic deposits postdating early Alpine orogenesis but predating the main tectonic-metamorphic evolution, end of nappe emplacement, unroofing, and exhumation of the metamorphic units of the Betic-Rif Orogen. Two conglomerate intervals within these deposits are characterized by clasts of sedimentary, epimetamorphic, and mafic volcanic rocks derived from Malaguide-Ghomaride units and by clasts of acidic magmatic and orthogneissic rocks of unknown provenance, here studied. Magmatic rocks originated from late-Variscan two-mica cordierite-bearing granitoids and, subordinately, from aplitic dikes. Orthogneisses derive from similar plutonic rocks but are affected by an Alpine metamorphic overprint evolving from greenschist (T=510&j0;-530 degrees C and P=5-6 kbar) to low-temperature amphibolite facies (T>550&j0;C and P<3 kbar). Such a plutonic rock suite is unknown in any Betic-Rif unit or in the basement of the Alboran Sea, and the metamorphic evolution in the orthogneisses is different from (and older than) that of Alpujarride-Sebtide rocks to which they were formerly ascribed. Magmatic and metamorphic rocks very similar to those studied characterize the basements of some Kabylia and Calabria-Peloritani units. Therefore, the source area is a currently lost continental-crust realm of Calabria-Peloritani-Kabylia type, located to the ESE of the Malaguide-Ghomaride Domain and affected by a pre-latest Oligocene Alpine metamorphism. Increasingly active tectonics transformed this realm into rising areas from which erosion fed small subsiding synorogenic basins formed on the Malaguide-Ghomaride Complex. This provenance analysis demonstrates that all these domains constituted a single continental-crust block until Aquitanian-Burdigalian times, before its dispersal around nascent western Mediterranean basins.

Journal Article↗
PubMed2000

Maternal chromosome 7 hetero/isodisomy in Silver-Russell syndrome and PEG1 biallelic expression.

Silver-Russell syndrome (SRS) is characterized by a severe intrauterine and postnatal growth retardation, relative macrocephaly associated with 'mild' facial anomalies. The diagnostic importance of skeletal asymmetry remains controversial. The aetiology of the syndrome is heterogeneous. Maternal uniparental disomy of chromosome 7 (mUPD7) has been reported in approximately 7% of patients, but two carriers of chromosomal abnormalities involving the band 17q25 have also been described. We investigated a clinically selected sample of 20 SRS patients for the presence of mUPD7 using polymorphic microsatellite markers spanning the whole chromosome. Maternal UPD7 was found in only one patient corresponding to an incidence of 5%. The allelic distribution in this patient was consistent with heterodisomy. Segregation analysis of chromosome 14 and 16 showed a biparental contribution in all the 20 patients. Blood RNA from the mUPD7 patient and a normal donor were evaluated for the expression of Paternally Expressed Gene (PEG1), an imprinted gene on chromosome 7q32. Biallelic expression of the gene in adult blood tissues was found in both samples. Our results confirm the causal role of mUPD7 in a minority of SRS patients.

Abnormalities, Multiple↗
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

Nitric oxide pathway, Ca2+, and serotonin content in platelets from patients suffering from chronic daily headache.

An alteration in serotonin concentration has been found in patients with chronic headache caused by abuse of analgesic substances as well as an up-regulation of 5HT2 platelet receptors, which has been correlated with chronicization of the headache. In a previous study we demonstrated an increase in L-arginine/nitric oxide (NO) pathway activity in platelets from patients affected by migraine with or without aura, particularly during attacks. In the present research we assessed the variations in platelet L-arginine/NO pathway and cyclic guanosine monophosphate (cGMP) levels in 32 patients affected by chronic daily headache (CDH) (8 M, 24 F, age range 34-50 years) both during and between attacks. In these same patients, the platelet aggregation to different collagen concentrations (0.3, 1, 3 micrograms/ml) was determined as well as the intracellular platelet calcium concentration using fluorescence polarization spectrometry. These parameters were compared with those of an age- and sex-matched control group (n = 25; n = 10, n = 15, age range 35-51 years). A reduction found in platelet aggregation response to each collagen concentration used (p < 0.001) was coupled with an increased NO and cGMP production (NO: p < 0.0001; cGMP: p < 0.001). This was accompanied by a significant increase in intracytosolic Ca2+ (p < 0.0001) concentration and a reduced platelet serotonin content compared to those in control individuals (p < 0.0002). Changes in the above platelet parameters were accentuated more in patients with analgesic abuse than in CDH patients with no drug abuse. These findings suggest the occurrence of an activation of cGMP-Ca2+ mediated events in CDH patients with analgesic abuse. This physiologic compensatory mechanism, which intervenes in overcoming the increase in cytosolic Ca2+ levels, is not as efficient at limiting serotonin depletion by platelet dense bodies. A similar depletion in the central serotoninergic pathway can be assumed in the same patients.

Adult↗
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↗