Biomedical subjects

J Rossi

Publications and source records attributed to J Rossi.

At least 19 recordsLinked to original sources

PubMed1999

Repeated exposure of rats to JP-4 vapor induces changes in neurobehavioral capacity and 5-HT/5-HIAA levels.

Thirty-two Sprague-Dawley rats were exposed for 6 h/d for 14 consecutive days to JP-4 jet fuel vapor (2 mg/L) or room air control conditions. Following a 14- or 60-d recovery period, rats completed a battery of 8 tests selected from the Navy Neurobehavioral Toxicity Assessment Battery (NTAB) to evaluate changes in performance capacity. Exposure to JP-4 vapor resulted in significant changes in neurobehavioral capacity on several tests that varied as a function of the duration of the recovery period. Rats were evaluated for major neurotransmitter and metabolite levels in five brain regions and in the blood serum. Levels of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were shown to be significantly elevated in several brain regions as well as in the blood serum in the vapor-exposed groups. Results of the rat study are compared to previously reported neurobehavioral evaluations of European manufacturing personnel exposed chronically to jet fuel vapor.

Adaptation, Ocular↗

PubMed1999

Treatment results in childhood acute lymphoblastic leukemia with a modified ALL-BFM'90 protocol: lack of improvement in high-risk group.

We report results achieved in our institution with an acute lymphoblastic leukaemia risk-oriented treatment trial opened in January 1990 and closed on December 1995. The study was similar to the German ALL-BFM'90, except for using Protocol III for the standard-risk group, 2 g/m2 of methotrexate in Protocol M, and preventive cranial irradiation for the high-risk group only. The high-risk group included mostly patients with prednisone poor initial response and/or adverse cytogenetic features. This analysis included 374 patients, whose mean age was 6 years (range: 1 month-17 years). The overall complete remission rate was 94.4% (353/374) and the 5-year event-free survival (standard error) probability is 64(5)%. The 5-year event-free survival estimates for each risk group were: (1) high-risk group 37(5)%; (2) intermediate-risk group 66(1)%; and (3) standard-risk group 74(4)% (P = 0.0001). There are significantly higher-rates of isolated bone marrow and testicular relapses in the high-risk subset of patients. Our dismal results and the published experience, lead us to conclude that the optimal treatment for these high-risk acute lymphoblastic leukaemia patients is not currently known.

Adolescent↗

PubMed1999

Retarded growth and deficits in the enteric and parasympathetic nervous system in mice lacking GFR alpha2, a functional neurturin receptor.

Glial cell line-derived neurotrophic factor (GDNF) and a related protein, neurturin (NTN), require a GPI-linked coreceptor, either GFR alpha1 or GFR alpha2, for signaling via the transmembrane Ret tyrosine kinase. We show that mice lacking functional GFR alpha2 coreceptor (Gfra2-/-) are viable and fertile but have dry eyes and grow poorly after weaning, presumably due to malnutrition. While the sympathetic innervation appeared normal, the parasympathetic cholinergic innervation was almost absent in the lacrimal and salivary glands and severely reduced in the small bowel. Neurite outgrowth and trophic effects of NTN at low concentrations were lacking in Gfra2-/- trigeminal neurons in vitro, whereas responses to GDNF were similar between the genotypes. Thus, GFR alpha2 is a physiological NTN receptor, essential for the development of specific postganglionic parasympathetic neurons.

Animals↗

PubMed1999

False-positive beta-lactamase results with Staphylococcus lugdunensis in the Vitek AutoMicrobic system.

The Vitek AutoMicrobic system in combination with the Gram-positive susceptibility card detects beta-lactamase in staphylococci by utilizing penicillin as the substrate coupled with oxacillin as an inducer. The beta-lactamase activity of 21 clinical isolates and two reference strains of Staphylococcus lugdunensis was determined with this automated system and compared with a liquid nitrocefin assay after induction with oxacillin. Eight (38%) clinical isolates and the reference strain ATCC 49576 of S. lugdunensis showed production of beta-lactamase in both tests. Thirteen (62%) clinical isolates and the type strain ATCC 43809 were nitrocefin-negative. The Vitek AutoMicrobic system reported false-positive beta-lactamase results for 9 of those 13 isolates and for the type strain of S. lugdunensis. Results for disk diffusion (ampicillin) were concordant with the nitrocefin assay. With one exception, the MICs for penicillin of the nitrocefin-negative strains were in the equivocal range of 0.06-0.12 mg/l according to NCCLS. However, none of the nitrocefin-negative and Vitek-positive strains revealed any of the known staphylococcal genes for beta-lactamase as investigated by Southern hybridization, supporting the fact that false-positive beta-lactamase results may occur in the Vitek AutoMicrobic system. We conclude from our data that it may be justified to include S. lugdunensis in the quality control of Vitek cards containing beta-lactamase tests.

Diffusion↗

PubMed1999

mRNA localization signals can enhance the intracellular effectiveness of hammerhead ribozymes.

Subcellular localization signals for several mRNAs are positioned in their 3' untranslated regions (UTR). We have utilized the human alpha- and beta-actin 3' UTRs as signals for colocalizing hammerhead ribozymes with a lacZtarget mRNA. Ribozyme and target genes containing matched or unmatched 3' UTRs were cotransfected into 12-day-old chicken embryonic myoblast and fibroblast (CEMF) cultures and assayed by in situ hybridization (ISH) using a dual label, antibody sandwich procedure, and dual fluorescence microscopy to monitor intracellular colocalization. Beta-galactosidase localization in transfectants was visualized by incubation with X-gal and also quantitated by an o-nitrophenyl beta-D-galactopyranoside (ONPG) assay. We found that the percentage of colocalization using the matched alpha- or beta-actin 3' UTR (alpha-alpha or beta-beta) was enhanced approximately threefold relative to unmatched 3' UTRs. The increase in ribozyme-mediated inhibition of beta-galactosidase activity observed when matched 3' UTRs were used was consistent with the observed percentage of colocalization. These results represent the first direct demonstration that mRNA localization signals (zipcodes) can be utilized to enhance intracellular ribozyme efficacy.

3' Untranslated Regions↗

PubMed1999

Successful related umbilical cord blood transplantation for graft failure following T cell-depleted non-identical bone marrow transplantation in a child with major histocompatibility complex class II deficiency.

Major histocompatibility complex (MHC) class II deficiency is a rare form of primary combined immunodeficiency that can only be corrected by stem cell transplantation. We report a 4(1/2)-year-old girl with MHC class II deficiency who underwent a related CBT due to graft failure following T cell-depleted non-identical BMT. The patient is alive and well 2 years after the second transplant. A sustained hematopoietic engraftment and a progressive immune recovery have been detected. We conclude that cord blood may be an effective source of hematopoietic stem cells for patients with immuno- deficiency disorders including diseases with a high rate of graft failure.

Bone Marrow Transplantation↗

PubMed1999

Inhibition of phospholipase C-gamma1 activation blocks glioma cell motility and invasion of fetal rat brain aggregates.

OBJECTIVE: Phospholipase C (PLC)-gamma is a cytosolic enzyme activated by several growth factor (GF) receptors (epidermal GF receptor [EGFR], platelet-derived GF receptor, and insulin-like GF 1 receptor), and its activation is associated with increased cell motility (but not cell proliferation) in nonglioma cell lines. Because up-regulated activation of EGFR has been consistently linked to poor patient survival in patients with glioblastoma multiforme (GBM) and because inhibition of EGFR activation by tyrosine kinase inhibitors prevents glioma infiltration in vitro, we hypothesized that inhibition of PLC-gamma activation would inhibit glioma cell invasiveness. METHODS: Our experimental model assesses tumor spheroid invasion of fetal rat brain spheroids by confocal microscopy. We treated U87 GBM spheroids, and those derived from a single patient, with the PLC inhibitor U73122. We also transfected rat C6 glioma cells with the PLCz complementary deoxyribonucleic acid coding for a dominant negative PLC-gamma1 src-homology-2/src-homology-3 peptide fragment, which blocks binding and activation of PLC-gamma1 by GF receptors. Two clones (C6F and C6E) were grown into spheroids and were tested for invasiveness in the spheroid model and for responsiveness to GFs in a standard in vitro motility assay. RESULTS: The infiltration rate of the patient GBM cell line overexpressing wild-type EGFR was reduced by 2 micromol/L U73122 from a slope (percent invasion/h) of 0.74+/-0.08 (with the inactive congener U73343) to 0.04+/-0.053 (P = 8 x 10(-7) by two-tailed t test, 92% reduction); the integral rate, another measure of invasion, was reduced from 49.7+/-13 percent-hours per hour to 13.6+/-12 (P = 0.002, 72% reduction). The U87 spheroid invasion rate was reduced by 0.5 micromol/L U73122 from 46.7+/-8.5 percent-hours per hour to 11.2+/-4.6 (P = 3 x 10(-5)); the slope decreased from 1.7+/-0.41 percent per hour to 0.35+/-0.14 (P = 0.0001). The C6F and C6E clones demonstrated attachment to and "surrounding" of the fetal rat brain aggregate but no true invasion by confocal or light microscopy. PLCz blocked the motility response to epidermal GF, platelet-derived GF, and insulin-like GF. There was a significant decrease in PLC-gamma1-associated tyrosine phosphorylation. CONCLUSION: These results support a key role for PLC-gamma activation as a common postreceptor pathway for GF-induced tumor infiltration and further identify PLC-gamma1 as a possible target for anti-invasive therapy for GBMs.

Animals↗

PubMed1999

Potent inhibition of human immunodeficiency virus type 1 (HIV-1) gene expression and virus production by an HIV-2 tat activation-response RNA decoy.

Tat activation-response region (TAR) decoys have been developed for use in gene therapy for people infected with human immunodeficiency virus type 1 (HIV-1). When a TAR RNA decoy is overexpressed, it will bind Tat, thus leaving less of this crucial protein to bind to and activate the natural transcriptional promoter of HIV-1. Previous TAR decoy constructs have used HIV-1 TAR. However, recent epidemiological and biological data began to suggest that the TAR region from the human immunodeficiency virus type 2 (HIV-2) may suppress HIV-1 transcription and hence replication. We created a vector which overexpresses TAR-2 under the control of the human U6 small nuclear RNA gene promoter and here show that the U6-TAR-2 decoy construct potently inhibits both HIV-2 and HIV-1 gene expression. Further, this decoy construct is able to markedly suppress HIV-1 replication. Thus, we have directly proven that TAR-2 can suppress HIV-1 replication and suggest that the HIV-2 TAR decoy may prove useful for combating HIV-1 infection.

Acquired Immunodeficiency Syndrome↗

PubMed1999

Acute trilineage leukemia with monosomy of chromosome 7 following an acute promyelocytic leukemia.

We describe an 8 year old boy who had received chemotherapy for an acute promyelocytic leukemia and developed a secondary leukemia 27 months after the diagnosis of this first malignancy. Blasts cells were positive for cytoplasmic markers CD22, CD3 and myeloperoxidase. Cell surface T and myeloid-associated markers were also detected. Cytogenetic study disclosed monosomy 7. The patient achieved complete remission, but relapsed 15 months later with identical immunophenotypic and cytogenetic findings. Three-lineage commitment is proved by the expression of specific criteria for myeloid, and lymphoid T and B typing. A multipotent immature progenitor must be the target of leukemogenic agents. The prognosis is obviously ominous.

Antigens, CD↗

PubMed1999

[Modification of particle replacement in a case of benign paroxysmal positional vertigo (BPPV) of the horizontal canal].

A variant of the particle repositioning maneuver was used in a patient diagnosed as benign paroxysmal positional vertigo of the horizontal canal. The patient was treated initially with Lempert's maneuver, but a paradoxical response was elicited by videonystagmography so we had to develop a maneuver adapted to the location of the patients otoliths. The likely physiopathology is discussed in the light of videonystagmographic events.

Ear Canal↗

PubMed1999

Inhibition of spontaneous GABAergic transmission by trimethylolpropane phosphate.

Trimethylolpropane phosphate (TMPP) is a neuroactive organophosphate generated during partial pyrolysis of a synthetic ester turbine engine lubricant. While TMPP had been shown to have little affinity for acetylcholinesterase, previous binding studies and 6Cl- flux measurements have implicated TMPP as an antagonist of GABA, receptor/Cl- channels. Using the whole-cell patch clamp method, spontaneous inhibitory postsynaptic currents (sIPSCs) mediated by bicuculline-sensitive GABA(A) receptors were measured in neurons cultured from the rat embryonic hippocampus for 13-21 days. Experiments were conducted in the presence of tetrodotoxin and 6-cyano-7-nitroquinoxaline to inhibit spontaneous presynaptic action potentials and glutamate transmission, respectively, thus isolating GABAergic sIPSCs for study. TMPP induced a concentration-dependent inhibition of sIPSC amplitude and frequency suggesting both postsynaptic and presynaptic actions. Administration of 5 microM TMPP reversibly diminished sIPSC amplitude by 23 +/- 8% (mean SEM, n=5 cells) while markedly decreasing the mean sIPSC frequency by 40 +/- 2% (n=5). The mean time constant of sIPSC decay was reversibly decreased by 20 +/- 4% (n=3) in the presence of 20 microM TMPP, suggesting an increase in the rate of inactivation. To directly verify the blockade of ionotropic GABA receptors by TMPP, the effects of TMPP were examined on whole-cell Cl- current responses activated by exogenous GABA. Administration of TMPP (5 microM) depressed peak whole-cell GABA-induced currents to 73 1% (n=4) of control levels, consistent with the results on sIPSC amplitude. Our data directly demonstrate that TMPP directly inhibits GABA(A) receptor function, as indicated by the blockade of whole-cell GABA-mediated Cl- current and the reduction in sIPSC amplitude. Furthermore, TMPP exerts a presynaptic effect on GABAergic transmission, as evidenced by the reduction in sIPSC frequency, which may be independent of a GABA(A) receptor. The molecular basis for the presynaptic action of TMPP remains to be elucidated.

Animals↗

PubMed1998

Acute myeloid leukemia as a second malignancy: report of 9 pediatric patients in a single institution in Argentina.

BACKGROUND: Acute myeloid leukemia (AML) is well-recognized as one of the most important second malignancies. We report the occurrence of secondary AML (sAML) in our institution. PROCEDURE: From September 1987 to August 1996 we have observed sAML in 9 patients (median age 4 years), 5 of them previously treated for hematologic malignancies (group I): acute lymphoblastic leukemia (n = 2), AML (n = 1), non-Hodgkin lymphoma (n = 1). Hodgkin disease (n = 1), and 4 of these 9 patients treated for solid tumors (group II): neuroblastoma (n = 1), retinoblastoma (n = 1), Wilms tumor (n = 1), and central nervous system germinoma (n = 1). RESULTS: All the patients had topoisomerase II inhibitors as part of treatment of their first malignancy, but only 5 patients received epipodophyllotoxins. Alkylating agents were part of primary therapy in 8 of 9 patients. The latency period for the development sAML was 26.5 (range = 2-55) months. The morphologic FAB features of sAML were M5 (n = 5), M4 (n = 3), and M2 (n = 1). Cytogenetic studies showed r11q23 in 3 patients, all of them with prior hematological malignancies. Initial therapy for sAML in all cases was chemotherapy (including cytarabine in combination with idarubicin and etoposide or doxorubicin or mitoxantrone). Three patients died during induction and 6 achieved complete hematologic response. Three of these patients remain disease free at +15, +51, and +99 months post-remission (including one post allogeneic BMT). The remaining 3 patients died, 1 in complete remission one month after diagnosis and 2 relapsed and died with progressive disease (one post allogeneic BMT). CONCLUSIONS: Secondary AML is a sequela of oncologic treatments with specific cytogenetic abnormalities and poor outcome. A few patients can achieve long-term survival even with standard chemotherapy.

Acute Disease↗

PubMed1998

Antimould activity of sourdough lactic acid bacteria: identification of a mixture of organic acids produced by Lactobacillus sanfrancisco CB1.

Sourdough lactic acid bacteria, cultivated in wheat flour hydrolysate, produced antimould compounds. The antimould activity varied greatly among the strains and was mainly detected within obligately heterofermentative Lactobacillus spp. Among these, Lb. sanfrancisco CB1 had the largest spectrum. It inhibited moulds related to bread spoilage such as Fusarium, Penicillium, Aspergillus and Monilia. A mixture of acetic, caproic, formic, propionic, butyric and n-valeric acids, acting in a synergistic way, was responsible for the antimould activity. Caproic acid played a key role in inhibiting mould growth.

Antifungal Agents↗

PubMed1998

Repeated exposure to trimethylolpropane phosphate induces central nervous system sensitization and facilitates electrical kindling.

Trimethylolpropane phosphate (TMPP), pentylenetetrazol (PTZ) and N-methyl-beta-carboline-3-carboxamide (FG-7142) were evaluated and compared for facilitation of electrical kindling in freely moving rats. Stimulating/recording electrodes were implanted in the left amygdala (LAD), right amygdala (RAD) and left bed nucleus (LBN) of the stria terminalis. TMPP (0.275 mg/kg), PTZ (20 mg/kg), FG-7142 (7.5 mg/kg) or vehicle was administered intraperitoneally (i.p.) to separate groups of rats 3 times/week for 10 weeks. Stimulation of the LAD (0.1 Hz, 0.1-ms duration, 280-1500 microA, 20 pulses) 24 h following the drug administration evoked epileptiform after-discharges (ADs) in the LBN and RAD of 12.5% and 17% of rats after the seventh dose of TMPP and PTZ, respectively, and in 20% of rats from the LBN and RAD after the ninth and nineteenth dose of FG-7142, respectively. The same stimulation also induced myoclonic jerks after nine doses of TMPP or PTZ, or after thirteen doses of FG-7142 in 25%, 30% and 20% of animals tested, respectively. Chemically kindled clonic seizures were observed in 100% of TMPP or FG-7142 and 50% of PTZ treated rats by the thirtieth dosing. Control animals exhibited neither behavioral nor electrographic seizures to vehicle injection or to the LAD stimulation. Kindling stimulation applied to the LAD (60 Hz, 2-s train duration, 20-1500 microA, 0.1-ms pulse duration) 4 weeks following the completion of drug treatments evoked epileptic after-discharges from the LAD, LBN and RAD in all treated groups, with generally decreased threshold and latency to onset of after-discharges, compared to vehicle controls. The present study suggests that repeated exposure of rats to sub-convulsive doses of TMPP, PTZ and FG-7142 induces long-term central nervous system sensitization that may be related to both chemical kindling and the facilitation of electrical kindling.

Animals↗

PubMed1998

Receptor ligand-facilitated cationic liposome delivery of anti-HIV-1 Rev-binding aptamer and ribozyme DNAs.

We examined whether HIV-1 gene expression could be inhibited by the anti-HIV Rev-binding aptamer [RBE(apt)], and whether the antiviral effect of the aptamer could be enhanced by a ribozyme directed against the HIV-1 env gene. Since cationic liposomes are relatively safe and non-immunogenic for in vivo gene delivery, we tested the effectiveness of the aptamer and ribozyme DNAs in HeLa cells, using Lipofectin reagent in a transient transfection assay. To increase the transfection efficiency, lipofectin was mixed with transferrin before subsequent addition of DNA. Co-transfection of HeLa cells with the RBE(apt) and the proviral HIV clone, HXBdeltaBgl, resulted in inhibition of virus production. Specific inhibition of viral p24 production following co-transfection of the RBE(apt) and HIV proviral DNAs was observed. These data provide strong support for the use of in vitro evolved ligands as potential anti-HIV agents. The addition of the anti-env ribozyme to the aptamer construct did not further enhance the antiviral activity, suggesting either that we had reached the limits of inhibition in this assay, or that the ribozyme was not able to access its target site with Rev bound to the RBE aptamer. The observed inhibition of p24 production could not be attributed to the non-specific toxicity of the transfection procedure, because no difference in viability was observed between the RBE(apt)- and the vector control-treated cells. All of the aptamer-ribozyme constructs as well as the RBE(apt) were similarly effective.

Base Sequence↗

PubMed1998

Trimethylolpropane phosphate (TMPP) perfusion into the nucleus accumbens of the rat: electroencephalographic, behavioral and neurochemical correlates.

The infusion (0.13 mumol/infusion) of the convulsant trimethylolpropane phosphate (TMPP) into the nucleus accumbens (NA) of adults Sprague-Dawley rats reliably induced subclinical seizures, hyperlocomotor activity, and integrated stereotypies. Observation of these behaviors was temporally correlated with the appearance of EEG paroxysms, as well as with significant decreases in extracellular concentrations of both dopamine (DA) and norepinephrine (NE) in the NA. Repeated perfusion of TMPP revealed significant increases in stereotypic behavior during subsequent pre-drug baseline testing.

Animals↗

PubMed1998

[Cavernous hemangioma of the maxillary sinus].

A 67-year-old man had an intraosseous giant cavernous hemangioma in maxillary sinus. We describe the MRI features of the case and note the potential risk of performing office biopsies on such lesions. Our patient did not have profuse hemorrhage and preventive measures were taken.

Aged↗

PubMed1998

Tissue distribution, metabolism, and clearance of the convulsant trimethylolpropane phosphate in rats.

The distribution, metabolism, and clearance of trimethylolpropane phosphate (TMPP), a potent, bicyclophosphate, gamma-aminobutyric acid-ergic convulsant, were studied in male Fischer-344 rats. Intraperitoneal administration of TMPP was compared with oral gavage with respect to rates of absorption, distribution, and clearance. Distribution of TMPP to major body tissues was evaluated for the first 24 hr after administration or, in the case of regional brain distribution, immediately after the first TMPP-induced clinical seizure. Samples purified from the urine, feces, and bile of rats exposed to TMPP, as well as from rat liver microsomes incubated with TMPP in vitro, were analyzed for possible phase I and phase II metabolism, using HPLC. The disposition and clearance of TMPP in the blood and major body tissues were measured. TMPP was found to be well distributed to highly vascularized tissue compartments, with little retention >24 hr after administration. TMPP was eliminated through the urine and feces as the parent compound, with no evidence of phase I or phase II metabolism. TMPP was rapidly cleared from the blood during the first 30 min after exposure, with slower clearance of >87% of the drug during the following 8-hr period and >99.5% clearance by 100 hr after injection. Repeated daily exposure to TMPP for up to 5 successive days resulted in no measurable accumulation in the brain or other major tissue compartments. Possible mechanisms for TMPP-induced, short- and long-term, neurobehavioral modulation are discussed.

Administration, Oral↗