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Biomedical subjects

C Rossi

Publications and source records attributed to C Rossi.

At least 145 records · Page 8Linked to original sources

Proton nuclear magnetic resonance spectral profiles of urine in type II diabetic patients.

Serial urine samples of 33 type II diabetic patients and 20 control subjects were examined by 1H nuclear magnetic resonance (NMR). Metabolites including lactate, citrate, glycine, alanine, hippurate, trimethylamine-N-oxide, and dimethylamine were identified in all subjects although in higher concentrations in diabetic patients. Other analytes, such as creatine, acetate, betaine, and ketone bodies, were found more frequently and in greater concentrations in diabetics than in controls. In addition, although lactate, citrate, alanine, and hippurate concentrations increased with increasing glycosuria and glycohemoglobin, trimethylamine-N-oxide and dimethylamine were present at high concentrations even in diabetics with good metabolic control. 1H NMR spectroscopy permitted us to explore the relationships among the metabolites present in the urine samples and to obtain information about the disease status in type II diabetic patients.

Aged↗

1H NMR spectra of normal urines: reference ranges of the major metabolites.

Serial urine samples from 50 normal subjects were studied by 1H NMR spectroscopy operating at 300 MHz. Analyses of the spectra have shown the presence of the following metabolites in 100% of the normal subjects: Creatinine, lactate, alanine, citrate, dimethylamine, trimethylamine-N-oxide, glycine and hippurate. Other analytes, such as creatine, valine, betaine, leucine and isoleucine, were sometimes found. All metabolites were quantified on the basis of peak heights and were expressed as mmol/mol of creatinine. The study of metabolic profiles in serial samples allowed us to evaluate intra-individual variability and physiological changes due to feeding. The aim of our report is to define standard conditions for this analytical technique and to calculate confidence intervals for the major metabolites in normal urine samples, such as preliminary and mandatory stages for clinical diagnostic 1H NMR utilization.

Adult↗

Dengue fever in US military personnel in Haiti.

OBJECTIVE: To describe clinical manifestations and public health implications of an outbreak of dengue fever (DF) during Operation Uphold Democracy, Haiti, 1994. DESIGN: Consecutive sample. SETTING: Military combat support hospital, Port-au-Prince, Haiti. PATIENTS: A total of 101 US military personnel with acute febrile illnesses. INTERVENTIONS: A disease surveillance team collected clinical and epidemiologic data from US military clinics throughout Haiti. Febrile patients admitted to the combat support hospital were evaluated with standardized clinical and laboratory procedures. The surveillance team followed patients daily. MAIN OUTCOME MEASURES: Arbovirus isolation and specific antibody determination and symptoms and physical findings. RESULTS: Febrile illnesses accounted for 103 (25%) of the 406 combat support hospital admissions during the first 6 weeks of deployment. All patients with febrile illness recovered. A total of 30 patients had DF; no patient had evidence of infection with malaria. Dengue virus serotypes 1, 2, and 4 were isolated from 22 patients, and 8 patients developed IgM antibody to dengue virus. Patients with DF could not be distinguished from other febrile patients on clinical grounds alone. No arboviruses other than dengue were identified. CONCLUSIONS: Active surveillance, with clinical and laboratory evaluation directed by an epidemiologic team, led to the timely recognition of an outbreak of febrile illness among US troops in Haiti. Viral isolation and serological studies were essential in confirming DF. During the surveillance period, DF accounted for at least 30% of the febrile illnesses among hospitalized US troops. Dengue fever is a significant threat to military personnel and civilian travelers in Haiti and has the potential for introduction to and transmission in the United States.

Adult↗

Modulation of mitomycin C mutagenicity on Saccharomyces cerevisiae by glutathione, cytochrome P-450, and mitochondria interactions.

It is well established that most anticancer drugs also have mutagenic effects and require metabolic activation before exerting their mutagenic/antiblastic activity. Antitumoral compound effects strongly depend on the biochemical/physiological conditions of the tumoral cells, and especially on the activation of specific drugs metabolizing enzymes and on respiration. We examined the mitomycin C-induced mutagenic effects on the D7 strain of Saccharomyces cerevisiae and on its derivative mitochondrial mutant p degrees at different contents of glutathione and cytochrome P-450, molecules able to activate/detoxicate xenobiotics. The mutagenic activity of the drug was evaluated as frequency of mitotic gene conversion and reversion in different physiological conditions. The highest frequencies of reversion and especially of gene conversion were observed at the highest cytochrome P-450 contents in the D7 strain with a further increase at high glutathione level. In the respiratory-deficient strain, the highest frequency of convertants was shown at low glutathione level and lack of cytochrome P-450. These results suggest the relevance of mitochondrial functionality for the expression of genotoxic activity of this anticancer drug.

Buthionine Sulfoximine↗

Illness awareness in cancer patients: a conceptual framework and a preliminary classification hypothesis.

The study describes the initial phases of research aimed at developing a methodology for assessing awareness in cancer patients. A first sample of cancer patients (n = 36) was interviewed about their knowledge of the diagnosis and their perception of treatment goals and outcomes. Thirteen domains which refer both to cognitive and emotional areas were identified, and considered as content valid by a panel of six experts. A second sample of patients (n = 54) participated in a semi-structured interview developed to explore awareness by means of the domains identified. Seven patterns of awareness were identified, ranging from 'completely aware patient' to 'completely unaware patient'. Twenty of the 54 patients (37.0%) were completely aware, 19 (35.2%) were partially aware with defence mechanisms and 15 (27.8%) were not aware of their diagnosis. Patients from the National Cancer Institute were more frequently aware (54.3%) compared with the patients interviewed in the community hospitals (5.3%) (p < 0.001). A computerized content analysis allowed the identification of two main groups of patients on the basis of the content of the recorded interviews. This independent classification agreed with the classification of the patients performed by the psychologists, suggesting the validity of the procedure of awareness evaluation proposed in this study.

Adaptation, Psychological↗

Thyroid cancer histotype changes as observed in a major general hospital in a 21-year period.

The existing registries of thyroid carcinoma are seldom comparable as far as epidemiological data, diagnostic criteria and histopatological description are concerned. Epidemiological studies report a progressive increase in the incidence of thyroid carcinoma in the last twenty years and in both sexes this increase of incidence has been referred to papillary histotype. Data collected from surgical series show a rate of thyroid carcinomas from 7 to 20% of total thyroid surgeries. The present study was designed in order to obtain a retrospective review of the distribution of thyroid carcinoma's different histotypes in the last 21 years in a major General Hospital. Detailed analysis of patients with histologically confirmed thyroid carcinoma admitted between 1974 and 1994 to the Surgery Department of Mauriziano Hospital of Torino, Italy showed an overall 11.8% prevalence of thyroid cancer out of the total thyroid surgeries. The rate of papillary carcinoma was the highest (54.3%) followed by follicular carcinoma (27.6%), anaplastic carcinoma (11.1%), medullary carcinoma (4.6%) and others (2.4%). The papillary-to-follicular ratio varied from 0.60 in 1974-76 to 6.88 in 1992-94. Female to male ratio of all thyroid carcinoma histotypes was 2.0 or more; papillary and follicular histotypes had the highest ratio. The variations of the histotype rate observed may be consequence of the silent increase of daily iodine intake throughout the subsequent years, while improved diagnostic tools available and increased experience of the medical staff have probably increased the number on thyroid ablations performed. Our data confirm the changing epidemiology of thyroid carcinoma, reported by international literature.

Adolescent↗

Genetic characterization and phylogeny of Andes virus and variants from Argentina and Chile.

Andes virus, one of five hantaviruses known to cause hantavirus pulmonary syndrome (HPS), emerged in 1995 in southwestern Argentina (López et al. (1996) Virology 220, 223-226). The complete nucleotide sequence of Andes virus S genome segment was determined and compared with sequences of viral RNAs in autopsy tissues of more recently reported HPS cases from southwestern Argentina and south of Chile (cases ESQ H-1/96 and CH H-1/96). Andes virus S segment was found to be 1876 nucleotides in length and to encode the nucleocapsid protein (N), 428 amino acids in length. S segment analysis also revealed a long 5' non-coding region (547 nucleotides) which displays three copies of an octanucleotide sequence repeat. Comparisons of S segment sequences of ESQ H-1/96 and CH H-1/96 (82% of the entire genome sequence) with the corresponding sequences of Andes virus revealed identities of 97.2% and 98.5%, respectively. Sequence motifs identical and in the same positions as exhibited in Andes virus 5' non-coding region were found in both, ESQ H-1/96 and CH H-1/96 sequences. Three genome fragments of the M segment sequence of the viruses (representing approximately 34% of the entire sequence) were also analyzed. Comparisons of S and M segment sequences of Andes virus with the corresponding sequences of ESQ H-1/96 showed S and M segment identities which differ by less than 1.4%. Andes virus and CH H-1/96 have S segments that differ by 1.5% from one another while their M segment fragments differ by 5.5-8.2%. Phylogenetic analysis showed that Andes virus along with ESQ H-1/96 and CH H-1/96 form a distinct lineage within the clade containing Bayou and Black Creek Canal viruses. It also showed that Andes virus branch of trees derived from comparisons of S or M sequences differed. It is concluded that Andes virus variants causing HPS circulate east and west of the Andes mountains.

Amino Acid Sequence↗

Spectral analysis of intercycle heart fluctuations in Xenopus laevis, conscious or spinalized, treated with calcium channel blockers. Part I.

1. In this study, electrocardiographic second lead tracings were recorded and analyzed online and offline in the conscious and spinalized Xenopus laevis under control conditions and after treatment with at least two effective doses of racemic diltiazem, nifedipine and racemic verapamil hydrochlorides. 2. Heart rates (HR) and intercycle heart rate power spectra (IHRPS) were calculated in the various experimental conditions. 3. Dose-dependent bradycardia was found in most cases, which was associated with dose-related increases in the overall dynamic range of the largest peak of HR variability (increased IHRPS), this being particularly marked at the higher nifedipine dose. The frequency position of the largest peak was unchanged in the spinalized preparation, as well as in the various treatments. 4. These findings may contribute toward a more complete pharmacodynamic definition of calcium channel blockers in their current therapeutic use.

Animals↗

Studies on the effect of the combined expression of anti-tat and anti-rev genes on HIV-1 replication.

A series of retroviral vectors with potential anti-tat and antirev activity was developed. Vectors containing a tat transdominant negative mutant (tat22/37) and an RRE decoy in different positions, directed by the same promoter or by different promoters, were generated. Retroviral vectors containing tat22/37 and the RevM10 transdominant negative mutant were also constructed. Jurkat cells were transduced with the recombinant retroviruses to produce monoclonal and polyclonal cultures. In these cell lines the recombinant proviruses were correctly integrated and expression of the inserted genes was detected by Northern blot or RT-PCR analysis. However, infection of these cell lines with HIV-1 showed that none of these recombinant constructs inhibited virus replication at a high multiplicity of infection (MOI). At a low MOI, two cell clones containing tat22/37 and the RRE decoy in 3' position showed a long lasting protection against virus replication, in comparison to control cultures expressing tat22/37 or RRE alone. Combination of tat and rev mutants was ineffective in inhibiting HIV-1 replication at both low and high MOIs. At a low MOI, HIV-1 replication was efficiently blocked in two cell clones expressing the RevM10 mutant alone. These results show a synergic effect of anti-tat and anti-rev molecules when the RRE sequence is cloned 3' to tat22/37, suggesting the possibility of using this vector design to control HIV-1 replication.

DNA, Recombinant↗

Inhibition of HIV-1 replication by a Tat transdominant negative mutant in human peripheral blood lymphocytes from healthy donors and HIV-1-infected patients.

It was previously shown that a tat mutant (tat22) where cysteine 22 is substituted by glycine behaves as a transdominant negative mutant in Jurkat T cells lytically or latently infected by HIV-1. In this study we demonstrate that tat22 controls HIV-1 replication in primary cells. This effect was observed both after in vitro infection of peripheral blood mononuclear cells (PBMCs) from normal donors and after reactivation of the latent infection in PBMCs from seropositive patients. The antiviral effect of tat22 was limited to conditions of low virus production. The use of tat22 may be promising for a gene therapy approach to AIDS during the asymptomatic phase of the disease allowing control of virus replication in infected cells and inhibition of virus spread to uninfected cells.

Gene Products, tat↗

Evaluation of a dipstick enzyme-linked immunosorbent assay for detection of antibodies to dengue virus.

Accurate serological confirmation of dengue (DEN) infection is difficult, because simple reliable assays for the detection of DEN antibodies are not available. To address this problem, a dipstick enzyme-linked immunosorbent assay (ELISA) was evaluated. The dipstick contained dots of serially diluted DEN 2 antigen. To detect immunoglobulin G (IgG), the dipstick was processed through four reaction cuvettes containing test serum, enhancer, enzyme-conjugated anti-human IgG and IgM antibody, and substrate. Total assay time was 45 min. To detect IgM, the serum was passed through a protein G device to remove IgG. The dipstick was then processed as before, except that the incubation times were longer and enzyme-conjugated anti-human IgM was used. The total assay time was 3 h. The dipstick ELISA results were compared with results from microplate ELISA. The IgG dipstick ELISA showed a sensitivity of 95.2% and a specificity of 100% compared to an IgG microplate ELISA with serum samples from 125 individuals living in an area in which DEN is endemic. In tests with 75 serum samples from patients with clinically suspected acute DEN infections, the IgM dipstick ELISA showed a sensitivity of 97.9% and specificity of 100% compared to those of an IgM antibody capture microplate ELISA. These results showed that the dipstick ELISA was a sensitive and specific test for the detection of either DEN IgM or IgG in human serum. The dipstick ELISA was also shown to be useful for detecting seroconversions to DEN IgM or IgG in paired serum samples from 20 patients with virus isolation-confirmed acute DEN infections.

Animals↗

Naked DNA vaccines expressing the prM and E genes of Russian spring summer encephalitis virus and Central European encephalitis virus protect mice from homologous and heterologous challenge.

Naked DNA vaccines expressing the prM and E genes of two tick-borne flaviviruses, Russian spring summer encephalitis (RSSE) virus and Central European encephalitis (CEE) virus were evaluated in mice. The vaccines were administered by particle bombardment of DNA-coated gold beads by Accell gene gun inoculation. Two immunizations of 0.5 to 1 microg of RSSE or CEE constructs/dose, delivered at 4-week intervals, elicited cross-reactive antibodies detectable by enzyme-linked immunosorbent assay and high-titer neutralizing antibodies to CEE virus. Cross-challenge experiments demonstrated that either vaccine induced protective immunity to homologous or heterologous RSSE or CEE virus challenge. The absence of antibody titer increases after challenge and the presence of antibodies to E and prM, but not NS1, both before and after challenge suggest that the vaccines prevented productive replication of the challenge virus. One vaccination with 0.5 microg of CEE virus DNA provided protective immunity for at least 2 months, and two vaccinations protected mice from challenge with CEE virus for at least 6 months.

Animals↗

Venezuelan equine encephalitis and Oropouche virus infections among Peruvian army troops in the Amazon region of Peru.

An outbreak of a febrile illness characterized by headache, ocular pain, myalgia, and arthralgia occurred during June 1994 among Peruvian army troops in Northern Peru. On June 14-16, 1994, clinical data and blood samples were obtained from eight soldiers with a febrile illness, and from 26 others who had a history of febrile illness during the past three months. A follow-up blood sample was obtained 107 days later from four of the febrile and seven of the afebrile soldiers. Serum samples were tested for dengue (DEN), Oropouche (ORO), and Venezuelan equine encephalitis (VEE) IgM and IgG antibodies by an enzyme-linked immunosorbent assay (ELISA). Virus isolation was performed by inoculation of newborn mice and Vero cell cultures. Viral isolates were identified by immunofluorescence, ELISA, and nucleotide sequencing. A VEE virus infection was confirmed in three of the eight febrile soldiers, two by virus isolation, and one by serology. Antigenic analysis indicated that one of the virus isolates was similar to VEE subtype I, variety ID, viruses previously isolated in Colombia and Venezuela. Nucleotide sequence data showed that both viral isolates were identical to one another and closely related to VEE ID viruses previously isolated in Peru, Colombia, and Venezuela. Serologic results showed that two of 26 afebrile soldiers had IgM antibody to VEE and four had IgG antibody to VEE; two febrile soldiers had IgG antibody in their first serum samples. Oropouche-specific IgM antibody was detected in one of the eight febrile and five of the afebrile soldiers, and 18 of the 34 soldiers had low titers of ORO IgG antibody titers, which did not meet the diagnostic criteria for confirmed cases. All soldiers were negative for DEN IgM antibody, and 10 had flavivirus IgG antibody that reacted with DEN antigens. These data indicated that VEE ID virus was one of the causes of illness among Peruvians soldiers and that this was the first association of this VEE subtype with human disease in Peru.

Adolescent↗

[Glutathione S-transferase mu 1 (GSTM1): susceptibility gene of breast cancer].

Glutathione S-transferases mu (GSTM) are dimeric cytosolic isoenzymes. They catalyze glutathione conjugation upon a large variety of electrophiles as carcinogens, trans-stilbene peroxide or benzo(a)pyrene. The gene GSTM1 is localized on chromosome 1p13, it has drawn attention because it is absent approximately in 50% of the white population. GSTM1 null genotype seems linked with susceptibility to cancers as lung, colon and bladder cancers. We have studied GSTM1 genotype from 373 primary breast tumours. The GSTM1 null genotype was found in 50% of the cases (185/373). The incidence study of GSTM1 copy number on clinical and biological variables displayed a significant difference (p < 0.01) of the GSTM1 genotype, showed by the tumour, according to the patient age at diagnosis. The patients younger than 55 years had a percentage more important of primary tumours (65%) with a copy number of GSTM1 gene, inferior or equal at one, compared to the patients older than 55 years (52%). The tumours, whose cathepsin D level was high, presented few copies of GSTM1 gene (p < 0.03). There was no other relationship, particularly, with tumour size, node status, histological type, hormonal receptors, pS2 cytosolic level GSTM1 gene seems protect the mammary gland from cancerogenesis with its detoxification role. This results had not, pointed out in breast cancer, yet.

Adult↗

Structural and thermodynamic characterization of the interaction of the SH3 domain from Fyn with the proline-rich binding site on the p85 subunit of PI3-kinase.

The interaction of the Fyn SH3 domain with the p85 subunit of PI3-kinase is investigated using structural detail and thermodynamic data. The solution structure complex of the SH3 domain with a proline-rich peptide mimic of the binding site on the p85 subunit is described. This indicates that the peptide binds as a poly(L-proline) type II helix. Circular dichroism spectroscopic studies reveal that in the unbound state the peptide exhibits no structure. Thermodynamic data for the binding of this peptide to the SH3 domain suggest that the weak binding (approximately 31 microM) of this interaction is, in part, due to the entropically unfavorable effect of helix formation (delta S0 = -78 J.mol-1.K-1). Binding of the SH3 domain to the intact p85 subunit (minus its own SH3 domain) is tighter, and the entropic and enthalpic contributions are very different from those given by the peptide interaction (delta S0 = +252 J.mol-1.K-1; delta H0 = +44 kJ.mol-1). From these dramatically different thermodynamic measurements we are able to conclude that the interaction of the proline-rich peptide does not effectively mimic the interaction of the intact p85 subunit with the SH3 domain and suggest that other interactions could be important.

Amino Acid Sequence↗

Kinetic analysis and comparison of models of xylose metabolism by Klebsiella planticola.

A model for the degradation of xylose and ethanol production by Klebsiella planticola is proposed and compared with the exponential and Michaelis-Menten approaches. This model is based on the energy system diagrams and it is a simplified version of a previous model developed for the glucose and ethanol kinetics of the yeast Saccharomices cerevisiae. In this model the dynamics of the substrate and of the final product are strictly related by means of the cellular activity. This model shows superior performances with respect to the two alternatives, behaving better along the whole dynamics.

Ethanol↗

Modeling interpretation of microbe metabolism detected by nuclear magnetic resonance.

A new modeling approach is discussed for the analysis of microbial dynamics. It is based on structurally nonlinear compartmental models and on the dynamics of the substrate and product. Experimental data were acquired by NMR spectroscopy which is a noninvasive technique. This combined approach was tested with the fermentation of glucose to ethanol by Saccharomyces cerevisiae. The model was fitted with the experimental data to obtain the values of the parameters of the model. Similar processes can be analyzed and compared using this approach.

Ethanol↗