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D Testa

Publications and source records attributed to D Testa.

At least 37 records · Page 2Linked to original sources
PubMed1996

Survival in multiple system atrophy: a study of prognostic factors in 59 cases.

The various clinical features of multiple system atrophy (MSA) make the diagnosis of the disease difficult, especially in its early stages, when signs of differentiated neuroanatomical system involvement have not yet appeared. Mortality studies may be affected by the variability of the diagnostic criteria and selection bias. We used strict clinical and MRI criteria to diagnose MSA in 59 patients. Patients with parkinsonian and cerebellar onset were compared. Median survival time from the onset of the first motor symptom was 7.5 years. Our results indicated a trend (P = 0.09) for the Northwestern University Disability Scale score to correlate with mortality, but we failed to find other characteristics identifying subgroups or predictors for survival.

Adult↗
PubMed1996

Type I interferon genes and proteins.

The large number of type I interferon genes in mammalian species could be explained by simple redundancy, by different functions for different interferons, or by different spatial or temporal patterns of expression. Different functions would require different receptors for each interferon, while different patterns of expression would require different transcriptional or postranscriptional regulatory mechanisms. It is also necessary to explain when and how this diversity was achieved. Information on comparative genetics of the interferon system, cloning of new interferon genes, studies on receptor interactions and studies on gene expression are accrued at each of the annual meetings of the ISICR. The last meeting held on October 2-7, 1994, at Budapest was not an exception, and this review summarizes some of this year's reports.

Animals↗
PubMed1996

Different relative activities of human cell-derived interferon-alpha subtypes: IFN-alpha 8 has very high antiviral potency.

Interferon-alpha (IFN-alpha) subtypes were separated by HPLC from the IFN mixtures produced by virus-stimulated human lymphoblastoid cells and leukocytes. Together with preparations of lymphoblastoid IFN and recombinant IFN-beta, these were tested in three human tumor cell lines derived from liver, lung, and neuroblasts. Their relative antiviral activities differed markedly: subtype IFN-alpha 8 was the most potent and IFN-alpha 1 the least. The results were broadly similar in all three cells, with some minor differences. when the same preparations were tested for inhibition of thymidine incorporation, the relative activities were quite different: subtypes IFN-alpha 10, IFN-alpha 17, IFN-alpha 21, and IFN-alpha 5 were now the most active, and IFN-alpha 2 was the least active. IFN-alpha 1 and IFN-alpha 8 had comparable intermediate activity. Thus, the differences in activity were not caused by degradation of some subtypes during their separation. IFN-alpha 8 not only had the greatest antiviral activity but also, like IFN-beta, induced an antiviral state in U1 mutant cell lines, which lack the tyrosine kinase, Tyk2, required for signal transduction by other IFN-alpha subtypes.

Antiviral Agents↗
PubMed1996

Regulation and characterization of the interferon-alpha present in patients with advanced human immunodeficiency virus type 1 disease.

To examine a possible association between plasma viremia and interferon-alpha (IFN-alpha) in patients with the acquired immunodeficiency syndrome (AIDS), we performed IFN plasma immunoadsorption by apheresis (IFN-alpha apheresis) in four volunteers with AIDS who had sustained levels of endogenous plasma IFN-alpha. IFN-alpha apheresis with two plasma volume exchanges was performed daily for 5 days. Clinical signs and symptoms and hematologic, virologic, and immunologic parameters were monitored. Two subjects developed anemia from phlebotomy, and one had a catheter++-associated bacteremia. The IFN-alpha apheresis was effective only in transiently removing IFN-alpha: depletion of IFN-alpha led only to its rapid reconstitution. Cell-associated HIV-1 was unchanged, but three of four subjects had a modest decrease in culturable plasma virus burden following the procedures. The recovery of in vivo HIV-1-related IFN-alpha by apheresis allowed its biologic and biochemical characterization. The HIV-1 IFN-alpha showed characteristics on ELISA, western blot, and biologic assays similar to two subspecies of the natural protein. The natural, recombinant, and HIV-1-induced IFN-alpha s demonstrated nearly identical antiviral activities. The HIV-1 IFN-alpha eluted from the column was not acid labile. The inability of large amounts of plasma IFN-alpha found in some patients with AIDS to affect viral burden likely reflects properties of the virus or of host factors independent of IFN-alpha.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Interferon-alpha 8b is the only variant of interferon-alpha 8 identified in a large human population.

Three variants of human interferon (IFN)-alpha 8a gene, that is, IFN-alpha 8b, and IFN-alpha 8c, have been reported previously. They differ from each other by changes in their coding region at nucleotide positions 359-360, 372, and 550. Human genomic DNA obtained from over 28,000 healthy blood donors and from 4 human cell lines was used in the polymerase chain reaction (PCR) designed for specific amplification of the IFN-alpha 8 gene fragments. The resulting PCR product was analyzed by (1) restriction endonuclease digestion, (2) DNA sequencing, and (3) allele-specific secondary PCR amplification. Only one sequence for IFN-alpha 8 was identified, and that was for IFN-alpha 8b. The sequences for IFN-alpha 8a and IFN-alpha 8c were not detected after PCR amplification either in the pooled leukocytes obtained from > 28,000 individuals or in cell lines tested. These data suggest that the naturally occurring variant or allele for IFN-alpha 8 in the population is IFN-alpha 8b. IFN-alpha 8a and IFN-alpha 8c variants were consistently below the level of detection of the assays and, if present at all in the population, are very rare.

Alleles↗
PubMed1996

Phase I trial of interferon alfa-n3 in early-stage human immunodeficiency virus type 1 disease: evidence for drug safety, tolerance, and antiviral activity.

The safety and tolerance of interferon alfa-n3 (IFN-alpha n3) was tested in 20 adults with asymptomatic human immunodeficiency virus type 1 (HIV-1) infection (> 400 CD4 lymphocytes/mm3). IFN-alpha n3 was self-injected three times per week for 3-6 months: 5 patients received 1 mega-IU (MIU)/dose, 10 received 5 MIU/dose, and 5 escalated to their maximum tolerated dose. Subjects were evaluated every 2-4 weeks through 2 months after cessation of treatment. Neuropsychological tests were given at 3-month intervals. Markers of IFN activity, anti-IFN neutralizing antibodies, and antiviral response were measured monthly. IFN-alpha n3 was safe and well tolerated: influenza-like symptoms were uncommon, laboratory toxicity was minimal, no adverse neurobehavioral side effects were evident, and no patient developed neutralizing antibodies against IFN. IFN-alpha n3 induced IFN-specific biologic responses and dose-related antiviral activity against HIV-1. Subjects showed stabilization of CD4 cells for > 20 months. IFN-alpha n3 should be studied in combination with other antiretroviral agents and in persons with more advanced HIV-1 infection.

Adult↗
PubMed1996

Suppressor T cell subsets in allergic rhinitis patients.

Lymphocyte T cell subsets, total and Parietaria IgE levels were studied in 68 allergic rhinitis patients. In treated patients we observed an increase in the lymphocyte T cell subsets, which express a suppressor function, defined by several monoclonal antibodies, i.e., CD8, CD8 + CD11b-, CD4 + CD62L+, CD4 + CD45RO. This increase was significant for T suppressor cells, CD8 + CD11b- (p < 0.046) and T memory cells, CD4 + CD45RO (p < 0.013), whereas a slight decrease was observed in the control group. A decrease in total serum IgE levels was observed in anti-H2 treated patients; only a slight increase was noted in placebo groups; and no variations were found in Parietaria levels in either group. In vitro culture of T lymphocyte clones, T memory cells, from atopic subjects produces IL-4, which induces an increase in IgE synthesis. An increase in T memory cells, observed in the treated group, should have accompanied an increase and not a decrease in total serum IgE levels, if the in vivo data correlated with those in vitro. Consequently, the behaviour of lymphocytes in vivo is not homologous to in vitro data.

Adolescent↗
PubMed1996

Comparison of SPT and NPT in the ascertainment of nasal mucosa as shock organ.

The Skin Prick Test (SPT) is the principal tool in allergic diagnosis, but in allergic rhinitisan immunological disease which affects 12% of the total population-the Nasal Provocation Test (NPT) allows more reliable results to be obtained. In our study a positive response to NPT has been found in four subjects with a history of symptoms suggesting allergic rhinitis, who had a negative SPT. Subjects with a positive SPT for two or more inhalant antigens have a significantly reduced number of antigen responses to NPT. Moreover, in two cases, the antigen than induced a positive response to NPT was different from the antigen that induced positive SPT. So. NPT is a reliable way of diagnosing allergic rhinitis. A more specific and reliable ascertainment of the antigen responsible for allergic reaction avoids unnecessary and ineffective immunotherapeutical attempts based on false assumptions.

Adolescent↗
PubMed1995

Competitor internal standards for quantitative detection of mycoplasma DNA.

Homologous internal controls were used as competitor DNA in the polymerase chain reaction for the quantitative detection of mycoplasma DNA. PCR primer sets were designed on the basis of the most conserved nucleotide sequences of the 16S rRNA gene of mycoplasma species. Amplification of this gene was examined in five different mycoplasma species: Mycoplasma orale, M. hyorhinus, M. synoviae, M. gallisepticum and M. pneumoniae. To evaluate the primers, a number of different cell lines were assayed for the detection of mycoplasma infections. All positive cell lines showed a distinct product on agarose gels while uninfected cells showed no DNA amplification. Neither bacterial nor eukaryotic DNA produced any cross-reaction with the primers used, thus confirming their specificity. Internal control DNA to be used for quantitation was constructed by modifying the sizes of the wild-type amplified products and cloning them in plasmid vectors. These controls used the same primer binding sites as the wild-type and the amplified products were differentiated by a size difference. The detection limits for all the mycoplasma species by competitive quantitative PCR were estimated to range from 4 to 60 genome copies per assay as determined by ethidium bromide-stained agarose gels. These internal standards also serve as positive controls in PCR-based detection of mycoplasma DNA, and therefore accidental contamination of test samples with wild-type positive controls can be eliminated. The quantitative PCR method developed will be useful in monitoring the progression and significance of mycoplasma in the disease process.

Base Sequence↗
PubMed1995

Clinical/metabolic correlations in multiple system atrophy. A fludeoxyglucose F 18 positron emission tomographic study.

OBJECTIVE: To evaluate the regional cerebral metabolic involvement; the relationships among regional brain metabolism, clinical features, and quantitative measures of disease severity; and the patterns of brain involvement that can be related to the different types of onset: striatonigral degeneration vs olivopontocerebellar atrophy. DESIGN: Fludeoxyglucose F 18 positron emission tomography (PET) studies performed in patients with multiple system atrophy (MSA) were evaluated for their clinical features at the onset of the disease and at the time of the PET study. CASES: Seventeen patients diagnosed as having probable MSA and 10 age-matched controls. RESULTS: The hypometabolism in the putamen-pallidum complex and in the cerebellum was the best discriminant for disease classification. The efficacy of levodopa treatment was positively correlated with the metabolic activity of the putamen-pallidum complex. The patients with olivopontocerebellar atrophy type (N = 8) had a prevalent hypometabolism in the cerebellum, while the patients with striatonigral degeneration type (N = 9) had a prevalent impairment in the pallidum-putamen complex. We demonstrated a negative correlation between (1) severity of parkinsonism and metabolic values of putamen and caudate; (2) severity of cerebellar signs and metabolism in the cerebellum; and (3) autonomic dysfunction and metabolic activity in the thalamus, frontal, and temporal regions, bilaterally. CONCLUSIONS: These findings support the selective metabolic reduction in the putamen and cerebellum as a marker of MSA. The clinical/metabolic correlations, demonstrating the expected dependence of extrapyramidal and cerebellar signs by dysfunction of basal ganglia and cerebellum, also support a possible involvement of central nervous system structures in autonomic control.

Atrophy↗
PubMed1995

Magnetic resonance signal abnormalities along the pyramidal tracts in amyotrophic lateral sclerosis.

Magnetic resonance imaging (MRI) studies of the brain were reviewed in 16 patients with amyotrophic lateral sclerosis (ALS), representative of a large and homogeneously studied series, 11 of whom showed signal abnormalities along the pyramidal tracts. These were more frequent in patients with more severe upper motor neuron signs but did not correlate with disease severity. Our study suggests that MRI signal abnormalities along the pyramidal tracts are common in ALS and may reflect the severity of pyramidal tract degeneration.

Amyotrophic Lateral Sclerosis↗
PubMed1995

Interferon-alpha 2 variants in the human genome.

Variants of human leukocyte interferon alpha 2 (IFN-alpha 2a, alpha 2b, and alpha 2c) differ from each other by changes in their coding regions at nucleotide positions 137 and 170. As a result of these nucleotide variations, the DNA sequences of the three variants can be distinguished by selective restriction enzyme analysis. Human genomic DNA obtained from over 28,000 normal healthy individuals was used as templates in the polymerase chain reaction (PCR) to amplify the human IFN-alpha 2 gene sequence. The resulting PCR products were analyzed with restriction nucleases to identify the specific IFN-alpha 2 variant sequences present in the genomic DNA of the population examined. The results show that IFN-alpha 2b was detected as the predominant species and IFN-alpha 2c as a very minor species (< 0.1%). The IFN-alpha 2a gene was not detected in this population.

Alleles↗
PubMed1995

Glutathione in the upper respiratory tract.

Glutathione (GSH), a major extracellular antioxidant, has been found in high concentrations in the epithelial lining fluid of the lower respiratory tract. The GSH concentrations in nasal fluid, in normal and pathologic conditions, were investigated and found to be very low. A GSH aerosol (600 mg daily for 10 days) increased GSH levels in the nasal mucosa and induced a statistically significant improvement in nasal obstruction, rhinorrhea, and ear fullness. Thus, GSH administered by aerosol could be a means of defending the epithelial respiratory cells against a toxic oxidant.

Adolescent↗
PubMed1995

[The treatment of benign laryngeal pathologies using CO2 laser in direct microlaryngoscopy with propofol-induced endovenous anesthesia in spontaneous respiration without intubation].

Direct microlaryngoscopy is an endoscopic technique with considerable diagnostic and surgical potentialities, which are increased when carbon-dioxide Laser is used, but often limited by the anaesthesiologic methods employed. In fact, the traditional anaesthesiologic technique, which uses small bore oral-tracheal tubes and provides good ventilation, has significant disadvantages: the tube often impedes surgical activity especially in the posterior regions of the larynx; stenoses of the larynx impede oral-thacheal intubation and thus require pre-operatory thacheotomy; administration of succinylcholine often induces diffused myalgia in the following 12-24 hours; administration of traditional narcotics always requires hospitalization. Jet-ventilation used by the Freach School as an alterative, while offering a more ample operatory space, is also accompanied by many disadvantages: vocal cords vibration; spray expulsion of smoke, blood, etc.; as with the traditional method, it cannot be employed in cases of laryngeal stenoses; succinylcholine often induces diffused myalgia; it cannot be used on out-patients. Introduction of Propofol, a new endovenous anaesthetic, the anaesthetologic pratice has permitted total endovenous anaesthesia to be achieved, in spontaneous respiration, without intubation. This method is indicated even in cases where the previously mentioned approaches are shown to be inadequate or impracticable. Narcosis with Propofol was used in 70 patients with benign laryngeal pathologies, belonging to the ASA risk classes I-II who underwent surgery via CO2 Laser during Microlaryngoscopy. The pharmacologic protocol of this narcosis require intravenous premedication with atropine and phentanyl, induction and continuation with Propofol and pharyngolaryngeal local anaesthesia with lidocaine spray. The advantages offered by this method are considerable: a completely free operative space; the possibility of being used in cases of laryngeal stenosis; a rapid return to consciousness; the absence of myalgia after surgery; the possibility of treating the disease on an out-patient basis. The absence of significant complications and the good results obtained lead us to propose this anaesthesiologic method as a valid alternative to anaesthesia by the traditional oral-tracheal intubation and to Jet ventilation.

Adult↗
PubMed1994

An open-randomized clinical trial of selegiline in amyotrophic lateral sclerosis.

Based on the hypothesis that free radicals play a general role in the neurodegenerative process in motor neuron disease, we tested selegiline in a group of patients affected by amyotrophic lateral sclerosis (ALS) to examine whether it might modify the progression of the disease. Patients were admitted if they were 25-80 years old and had a confirmed diagnosis of ALS with symptoms lasting no longer than 24 months. Patients with familial ALS, pure progressive bulbar palsy, primary lateral sclerosis or progressive muscle atrophy were excluded; a total of 111 patients were recruited. Fifty-three patients were randomly assigned to receive the drug (selegiline 10 mg/day orally for 6 months) and the remaining 58 were considered ALS controls. Mortality was similar in the two groups (4 and 5 patients respectively), though the difference was not statistically significant. Among the survivors, mean MRC and Norris disability scores and forced vital capacity were fairly similar in the two groups at all times and no statistically significant difference between treated and untreated patients was found. The results did not change when the data were related to age, duration and characteristics of onset of the disease. The rate of progression was significantly more rapid in patients with bulbar symptoms in both groups. Our data do not show any significant effect of selegiline in modifying the progression of ALS.

Adult↗
PubMed1994

Differing patterns of psychiatric impairment in Alzheimer and demented parkinsonian patients.

Psychiatric symptoms were investigated and compared in 95 patients with Alzheimer type dementia (DAT) and in 39 patients with Parkinson's disease with dementia (PD-D). The diagnosis of the dementia and psychiatric disorders was based on DSM III R criteria; dementia stage was assessed using the Clinical Dementia Rating Scale (CDR). PD-D were significantly older than DAT patients. Delirium was more frequent in the advanced stages of both PD-D and DAT, being mainly of the hypoactive type in PD-D and the hyperactive type in DAT. Delusions and hallucinations predominated in the early CDR stages of both illnesses and did not differ between groups; the same was true for depression. The results revealed different psychopathological profiles in DAT and PD-D patients.

Aged↗