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Biomedical subjects

J Rossi

Publications and source records attributed to J Rossi.

At least 55 records · Page 3Linked to original sources

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↗

[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↗

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↗

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↗

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↗

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↗

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↗

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↗

[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↗

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↗

Autocrine regulation of neural crest cell development by steel factor.

Steel factor (SLF) and its cognate receptor, c-kit, have been implicated in the generation of melanocytes from migrating neural crest (NC) cells during early vertebrate embryogenesis. However, the source of SLF in the early avian embryo and its precise role in melanogenesis are unclear. We report here that NC cells themselves express and release SLF protein, which in turn acts as an autocrine factor to induce melanogenesis in nearby NC cells. These results indicate that NC cell subpopulations play an active role in the determination of their cell fate and suggest a different developmental role for the embryonic microenvironment than what has been previously proposed.

Animals↗

Characterization of the substrate binding site of polyenoic fatty acid isomerase, a novel enzyme from the marine alga Ptilota filicina.

The substrate binding site of polyenoic fatty acid isomerase (PFI) has been investigated using a series of alternate substrates and by examination of the pH dependence on the kinetic parameters of PFI with selected substrates. The pH dependence profile of PFI with EPA [(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoic acid] shows the enzyme to be catalytically active over a wide pH range, with activity being optimal below pH 6.0. Analysis of the kinetic parameters of DHA [(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexen oic acid]; adrenic acid [(7Z,10Z,13Z,16Z)-docosatetraenoic acid]; EPA; arachidonic acid [(5Z,8Z,11Z,14Z)-eicosatetraenoic acid]; anandamide (arachidonyl-N-ethanolamide); and eicosatrienoic acid [(5Z,8Z,11Z)-eicosatrienoic acid] demonstrates that substrates possessing omega-3 olefins (DHA and EPA) have the lowest K(m) values (1.9 and 9.6 microM, respectively). EPA and arachidonic acid showed the highest V(max) values (6.0 and 2.8 micromol min(-1) mg(-1), respectively). The twenty carbon omega-9 fatty acid eicosatrienoic acid showed a relatively large K(m) and had a V(max) approximately 20-fold less than EPA. Anandamide, a substrate analog lacking an ionizable carboxylate, showed a K(m) similar to the other omega-6 fatty acids (arachidonic acid and adrenic acid); however, the V(max) was approximately 5-fold lower than arachidonic acid and 8-fold lower than EPA. Moreover, anandamide demonstrated no pH dependency on its kinetic parameters over a range where EPA showed a 27-fold decrease in V/K(m). NMR spectroscopy was used to determine the structure of the product from reaction of PFI with DHA. These data showed the compound to be (4Z,7Z,9E,11E,16Z,19Z)-docosahexenoi c acid. Reaction of PFI with dihomo-gamma-linolenic acid resulted in the development of two products, one with the characteristic chromophore of a conjugated triene, the other with a chromophore characteristic of a conjugated diene. Analysis of the products from these reactions of PFI, in conjunction with the kinetic parameters from the alternate substrates, provides compelling evidence that the enzyme preferentially orients the substrate in the catalytic site with respect to the methyl terminus.

Binding Sites↗

Lesions of the entorhinal cortex disrupt behavioral and neuronal responses to context change during extinction of discriminative avoidance behavior.

Rabbits given either electrolytic lesions of the entorhinal cortex or sham-lesions were trained to prevent a foot-shock by stepping in an activity wheel after one tone, a positive conditioned stimulus (CS+), and to ignore a different tone, a negative conditioned stimulus (CS-). Neuronal activity was recorded simultaneously in the basolateral nucleus of the amygdala, the CA1 cell field of hippocampus, anterior cingulate cortical area 24b and posterior cingulate cortical area 29c/d. The activity of neurons in the entorhinal cortex was recorded in the controls. Acquisition of conditioned avoidance responses (CRs) was not affected by lesions of the entorhinal cortex. Discriminative neuronal activity (greater neuronal responses to the CS+ than to the CS-) during CR acquisition was significantly enhanced in hippocampal area CA1 and attenuated in the basolateral amygdala in rabbits with lesions. Following acquisition to a criterion, two counterbalanced extinction tests were administered, one in the original context and the other in the presence of novel contextual stimuli. CR frequency was significantly reduced in controls but not in rabbits with lesions, during extinction with novel contextual stimuli, relative to performance in the original context. The rabbits with lesions also showed fewer inter-trial responses than controls during extinction in the original context but intertrial response frequency in rabbits with lesions did not differ from the frequency in controls during extinction in the novel context. Neurons in the basolateral amygdala in controls showed discriminative activity during extinction in the original context but not in the novel context. Amygdalar neurons in the rabbits with lesions did not show discriminative activity during extinction in either context. Posterior cingulate cortical neurons in control rabbits did not show discriminative activity during extinction in the original context but these neurons exhibited robust discriminative activity in the novel context. Posterior cingulate cortical neurons in rabbits with lesions showed discriminative activity in both extinction sessions. The results indicated that the entorhinal cortex does not play a significant role in the acquisition of discriminative avoidance behavior, under the employed conditions of training. However, the interactions of neurons in the entorhinal cortex, amygdala and cingulate cortex are essential for contextual modulation of CRs during extinction.

Amygdala↗

Testing the neural sensitization and kindling hypothesis for illness from low levels of environmental chemicals.

Sensitization in the neuroscience and pharmacology literatures is defined as progressive increase in the size of a response over repeated presentations of a stimulus. Types of sensitization include stimulant drug-induced time-dependent sensitization (TDS), an animal model related to substance abuse, and limbic kindling, an animal model for temporal lobe epilepsy. Neural sensitization (primarily nonconvulsive or subconvulsive) to the adverse properties of substances has been hypothesized to underlie the initiation and subsequent elicitation of heightened sensitivity to low levels of environmental chemicals. A corollary of the sensitization model is that individuals with illness from low-level chemicals are among the more sensitizable members of the population. The Working Group on Sensitization and Kindling identified two primary goals for a research approach to this problem: to perform controlled experiments to determine whether or not sensitization to low-level chemical exposures occurs in multiple chemical sensitivity (MCS) patients; and to use animal preparations for kindling and TDS as nonhomologous models for the initiation and elicitation of MCS.

Animals↗

Use of a hammerhead ribozyme with cationic liposomes to reduce leukocyte type 12-lipoxygenase expression in vascular smooth muscle.

Chemically synthesized hammerhead-type ribozymes targeted against the porcine leukocyte-type 12-lipoxygenase (LO) have been developed and studied. One chimeric ribozyme consists of DNA in the non-enzymatic portions, and RNA in the enzymatic core as well as two phosphorothioate internucleotide linkages at 3' terminus. The second ribozyme consists of ribonucleotide sequences generated by in vitro transcription. In this chapter we describe methodologies to first analyze the ribozyme catalytic activity in vitro by studying cleavage of target RNA in vitro. The subsequent sections will describe how to target the catalytic ribozyme and deliver it to porcine vascular smooth muscle cells (PVSMC) by a liposome-mediated method. Finally ways to evaluate its activity to inhibit expression of the 12-LO mRNA will be presented. These results demonstrate the feasibility of using ribozymes as novel candidates for therapeutic agents to block specific gene expression in vascular cells.

Animals↗