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Biomedical subjects

A Martini

Publications and source records attributed to A Martini.

At least 55 records · Page 3Linked to original sources
PubMed2001

In vivo neutralization of human IL-6 (hIL-6) achieved by immunization of hIL-6-transgenic mice with a hIL-6 receptor antagonist.

Neutralization of IL-6 represents an attractive therapeutic option in several diseases, including B cell neoplasia, osteoporosis, and autoimmunity. Therapeutic attempts in humans have shown that administration of injectable doses of a mAb to IL-6 does not provide efficient neutralization of the cytokine in vivo. Therefore, alternative approaches are needed. In this study, we evaluated whether the Ab response to human IL-6 (hIL-6) elicited by vaccination with Sant1 (a hIL-6 variant with seven amino acid substitutions) was able to fully correct in vivo the clinical and biological effects of a chronic endogenous overproduction of hIL-6 in the hIL-6-transgenic NSE/hIL-6 mice. Because of the overexpression of hIL-6, occurring since birth, with circulating levels in the nanogram per milliliter range, NSE/hIL-6 mice have a marked decrease in growth rate, associated with decrease in insulin-like growth factor I levels, and represent an animal model of the growth impairment associated with human chronic inflammatory diseases. Following immunization with Sant1, but not with hIL-6, NSE/hIL-6 mice developed high titers of polyclonal Abs to hIL-6. The Abs, acquired by transplacental transfer, effectively neutralized IL-6 activities in vivo as shown by the complete correction of the growth defect and normalization of insulin-like growth factor levels in the hIL-6-transgenic offspring. Immunization with Sant1 could therefore represent a novel and simple therapeutic approach for the specific neutralization of IL-6 in humans.

Amino Acid Substitution↗
PubMed2001

Juvenile systemic scleroderma.

Systemic scleroderma in children is very rare and is considered similar to adult-onset disease. In adults, new etiopathogenetic and therapeutic approaches have emerged in recent years. For instance, it has been shown that microchimerism could play a role in disease pathogenesis and that immunoablation followed by stem cell rescue could be of potential therapeutic benefit. There is also evidence that these new approaches can be of value for childhood-onset disease.

Adolescent↗
PubMed2001

Mapping of a new autosomal dominant nonsyndromic hearing loss locus (DFNA30) to chromosome 15q25-26.

Hearing impairment is the most common inherited human sensory defect. Nonsyndromic Hearing Impairment (NSHI) is the most genetically heterogeneous trait known. Over 70 loci have been mapped and a total of 19 genes have been identified. We report here a novel locus (DFNA 30) for autosomal dominant NSHI that we mapped to chromosome 15q25-26 in an Italian four-generation family. The haplotype analysis has identified a critical interval of 18 cM between markers D15S151 and D15S130. This region does not overlap with DFNB16 locus but partially coincides with the otosclerosis (OTS) locus. Localisation of the locus DFNA30 is a first step towards the identification of the gene.

Chromosome Mapping↗
PubMed2001

Efficient otoacoustic emission protocols employed in a hospital-based neonatal screening program.

Within the context of a hospital-based newborn hearing screening program, we have studied the application of two OAE protocols (TEOAE and DPOAE) on a group of 250 well babies. The main goal of this study was to evaluate the performance of DPOAE protocol in a relatively large population sample. using a preset number of five tested frequencies, in comparison with a default TEOAE screening protocol. The data were collected on the second day of life and during spontaneous sleep. The TEOAE recordings were acquired with linear protocols using click stimuli of 70-75 dB SPL and were used as indicators of normal cochlear function. The cubic distortion product DPOAE responses were evoked by an asymmetrical 75-65 dB SPL protocol, with a frequency ratio of 1.22. Five frequencies (referring to F2) were tested at 1.5, 2.0, 3.0, 4.0 and 5.0 kHz. The data from the DPOAE responses show a similar pass rate (similarity = 0.98) to the linear TEOAE protocol. The data presented suggest that a DPOAE cochlear evaluation, at 5 pre-selected frequencies, has clinical potential.

Deafness↗
PubMed2001

Large-scale screening of selected Candida maltosa, Debaryomyces hansenii and Pichia anomala killer toxin activity against pathogenic yeasts.

The killer activity of selected crude toxins produced by nine Candida maltosa, Debaryomyces hansenii and Pichia anomala strains was tested at 37 degrees C against 383 strains belonging to 19 pathogenic species of 10 genera (Candida, Clavispora, Cryptococcus, Filobasidiella, Issatchenkia, Kluyveromyces, Pichia, Saccharomyces, Stephanoascus and Trichosporon). The broad killer spectra exhibited by all crude toxins may lead to the development of new antimycotic agents against medically important yeasts.

Antifungal Agents↗
PubMed2001

Environmental and biological monitoring of traffic wardens from the city of Rome.

A molecular epidemiological study on Roman policemen is ongoing. The results of a first assessment of the occupational exposure to aromatic compounds of 66 subjects engaged in traffic control and of 33 office workers are presented in this paper. Passive personal samplers and urinary biomarkers were used to assess exposure to benzene and polycyclic hydrocarbons during work shifts. The results obtained indicate that benzene exposure in outdoor workers is about twice as high as in office workers (geometric mean 7.5 and 3.4 micrograms/m3, respectively). The distribution of individual exposure values was asymmetrical and skewed toward higher values, especially among traffic wardens. Environmental benzene levels recorded by municipal monitoring stations during work shifts (geometric mean 11.2 micrograms/m3) were in the first instance comparable to or greater than individual exposure values. However, several outlier values were observed among personal data that greatly exceeded average environmental benzene concentrations. Among the exposure biomarkers investigated, only blood benzene correlated to some extent with previous exposure to benzene, while a seasonal variation in the excretion of 1-hydroxypyrene and trans-muconic acid was observed in both study groups. In conclusion, these results suggest that outdoor work gives a greater contribution than indoor activities to benzene exposure of Roman citizens. Moreover, relatively high-level exposures can be experienced by outdoor workers, even in the absence of large-scale pollution episodes.

Adult↗
PubMed2001

Discordance between proxy-reported and observed assessment of functional ability of children with juvenile idiopathic arthritis.

OBJECTIVE: To determine the level of agreement between parents and clinicians in rating dysfunction in children with juvenile idiopathic arthritis (JIA). METHODS: A parent of each patient completed the Italian version of the Childhood Health Assessment Questionnaire (CHAQ). Subsequently, an examiner assessed, in a specially equipped room, the child's performance of tasks as described by the CHAQ. Demographic and clinical variables were recorded for all patients. RESULTS: Seventy consecutive JIA patients and their parents were included. The mean proxy-reported and observed CHAQ score was 0.64+/-0.53 and 0.47+/-0.62 respectively, the difference ranging from -1.75 to 1.5. There were 30 cases (43%) of agreement (difference < or =0.25 CHAQ units) between the parent's and clinician's ratings, whereas in 40 cases (57%) there was discordance (difference >0.25 CHAQ units). In 30 cases the parent rated the child's functional ability as worse than that observed by the clinician (i.e. the parent underestimated the child's function), whereas in 10 cases the parent rated the child's functional ability as better than that observed by the clinician (i.e. overestimated the child's function). Multivariate regression analysis showed that children's functional ability was overestimated by parents with increasing erythrocyte sedimentation rate and global articular severity score and underestimated with increasing level of pain. Among the functional areas of the CHAQ, the level of agreement was poorest in the areas of eating and hygiene and was best for activities. CONCLUSIONS: Discordance between proxy-reported and observed functional ability was frequent in our patients with JIA. The children's functional ability was overestimated by parents as the severity of arthritis increased and underestimated as the level of pain increased.

Adolescent↗
PubMed2001

Rapid methods to extract DNA and RNA from Cryptococcus neoformans.

Extraction of nucleic acids from the pathogenic yeast Cryptococcus neoformans is normally hampered by a thick and resistant capsule, accounting for at least 70% of the whole cellular volume. This paper presents procedures based on mechanical cell breakage to extract DNA and RNA from C. neoformans and other capsulated species. The proposed system for DNA extraction involves capsule relaxation by means of a short urea treatment and bead beating. These two steps allow a consistent extraction even from strains resistant to other procedures. Yield and quality of DNA obtained with the proposed method were higher than those obtained with two earlier described methods. This protocol can be extended to every yeast species and particularly to those difficult to handle for the presence of a capsule. RNA purification is accomplished using an original lysing matrix and the FastPrep System (Bio101) after a preliminary bead beating treatment. Yields range around 1 mg RNA from 15 ml overnight culture (10(9) cells), RNA appears undegraded, making it suitable for molecular manipulations.

Centrifugation↗
PubMed2001

Discrimination between Candida albicans and other pathogenic species of the genus Candida by their differential sensitivities to toxins of a panel of killer yeasts.

The differential sensitivities to toxins produced by a short panel of four killer yeasts allowed discrimination between 91 strains of the yeast Candida albicans and 223 non-C. albicans Candida strains. One hundred percent of C. albicans isolates exhibited negative results to the toxin panel, while 100% of non-C. albicans cultures gave well-defined and reproducible positive results to at least one of the four killer toxins. Among C. albicans strains only 96 and 87% gave germ tube (GT)- and chlamydospore-positive results, respectively. In addition a few GT-false-positive strains were detected among non-C. albicans isolates. Susceptibility to the toxin panel is apparently expressed more consistently than either GT or chlamydospore production and may constitute a promising basis for a new simple and easy-to-use procedure for routine discrimination between the species C. albicans and other species of the genus Candida.

Candida↗
PubMed2001

Phase I/II trial of autologous stem cell transplantation in systemic sclerosis: procedure related mortality and impact on skin disease.

BACKGROUND: Systemic sclerosis (SSc, scleroderma) in either its diffuse or limited skin forms has a high mortality when vital organs are affected. No treatment has been shown to influence the outcome or significantly affect the skin score, though many forms of immunosuppression have been tried. Recent developments in haemopoietic stem cell transplantation (HSCT) have allowed the application of profound immunosuppression followed by HSCT, or rescue, to autoimmune diseases such as SSc. METHODS: Results for 41 patients included in continuing multicentre open phase I/II studies using HSCT in the treatment of poor prognosis SSc are reported. Thirty seven patients had a predominantly diffuse skin form of the disease and four the limited form, with some clinical overlap. Median age was 41 years with a 5:1 female to male ratio. The skin score was >50% of maximum in 20/33 (61%) patients, with some lung disease attributable to SSc in 28/37 (76%), the forced vital capacity being <70% of the predicted value in 18/36 (50%). Pulmonary hypertension was described in 7/37 (19%) patients and renal disease in 5/37 (14%). The Scl-70 antibody was positive in 18/32 (56%) and the anticentromere antibody in 10% of evaluable patients. Peripheral blood stem cell mobilisation was performed with cyclophosphamide or granulocyte colony stimulating factor, alone or in combination. Thirty eight patients had ex vivo CD34 stem cell selection, with additional T cell depletion in seven. Seven conditioning regimens were used, but six of these used haemoimmunoablative doses of cyclophosphamide +/- anti-thymocyte globulin +/- total body irradiation. The median duration of follow up was 12 months (3-55). RESULTS: An improvement in skin score of >25% after transplantation occurred in 20/29 (69%) evaluable patients, and deterioration in 2/29 (7%). Lung function did not change significantly after transplantation. One of five renal cases deteriorated but with no new occurrences of renal disease after HSCT, and the pulmonary hypertension did not progress in the evaluable cases. Disease progression was seen in 7/37 (19%) patients after HSCT with a median period of 67 (range 49-255) days. Eleven (27%) patients had died at census and seven (17%) deaths were considered to be related to the procedure (direct organ toxicity in four, haemorrhage in two, and infection/neutropenic fever in one). The cumulative probability of survival at one year was 73% (95% CI 58 to 88) by Kaplan-Meier analysis. CONCLUSION: Despite a higher procedure related mortality rate from HSCT in SSc compared with patients with breast cancer and non-Hodgkin's lymphoma, the marked impact on skin score, a surrogate marker of mortality, the trend towards stabilisation of lung involvement, and lack of other treatment alternatives justify further carefully designed studies. If future trials incorporate inclusion and exclusion criteria based on this preliminary experience, the predicted procedure related mortality should be around 10%.

Adolescent↗
PubMed2001

Exposure to benzene in urban workers: environmental and biological monitoring of traffic police in Rome.

OBJECTIVES: To evaluate the contribution of traffic fumes to exposure to benzene in urban workers, an investigation on personal exposure to benzene in traffic police from the city of Rome was carried out. METHODS: The study was performed from December 1998 to June 1999. Diffusive Radiello personal samplers were used to measure external exposures to benzene and alkyl benzenes during the workshift in 139 policemen who controlled medium to high traffic areas and in 63 office police. Moreover, as biomarkers of internal exposure to benzene, blood benzene, and urinary trans, trans-muconic and S-phenyl mercapturic acids were measured at the beginning and at the end of the workshift in 124 traffic police and 58 office police. RESULTS: Time weighted average (TWA) exposure to benzene was consistently higher among traffic police than among indoor workers (geometric mean 6.8 and 3.5 microg/m(3), respectively). Among the traffic police, the distribution of individual exposures was highly asymmetric, skewed toward higher values. Mean ambient benzene concentrations measured by municipal air monitoring stations during workshifts of traffic police were generally higher (geometric mean 12.6 microg/m(3)) and did not correlat with personal exposure values. In particular, no association was found between highest personal exposure scores and environmental benzene concentrations. Among the exposure biomarkers investigated, only blood benzene correlated slightly with on-shift exposure to benzene, but significant increases in both urinary trans, trans-muconic and S-phenylmercapturic acids were found in active smokers compared with non-smokers, irrespective of their job. CONCLUSION: The exposure to traffic fumes during working activities in medium to high traffic areas in Rome may give a relatively greater contribution to personal exposure to benzene than indoor sources present in confined environments. Smoking significantly contributed to internal exposure to benzene in both indoor and outdoor workers.

Adult↗
PubMed2001

Effect of IL-6 on IGF binding protein-3: a study in IL-6 transgenic mice and in patients with systemic juvenile idiopathic arthritis.

Stunted growth is a common complication of childhood diseases characterized by chronic inflammation or infections. We previously demonstrated that NSE/hIL-6 transgenic mice, overexpressing the inflammatory cytokine IL-6 since early phase of life, showed a marked growth defect associated with decreased IGF-I levels, suggesting that IL-6 is one of the factors involved in stunted growth complicating chronic inflammation in childhood. Here we show that NSE/hIL-6 mice have normal liver IGF-I production, decreased levels of IGF binding protein-3 (IGFBP-3) and increased serum IGFBP-3 proteolysis. Reduced IGFBP-3 levels results in a marked decrease in the circulating 150-kDa ternary complex, even in the presence of normally functional acid labile subunit. Pharmacokinetic studies showed that NSE/hIL-6 mice have accelerated IGF-I clearance. Patients with systemic juvenile idiopathic arthritis (s-JIA), a chronic inflammatory disease characterized by prominent IL-6 production and complicated by stunted growth associated with low IGF-I levels, have markedly decreased IGFBP-3 levels, increased serum IGFBP-3 proteolysis and normal acid labile subunit levels. Our data show that chronic overproduction of IL-6 causes decreased IGFBP-3 levels, resulting in a decreased association of IGF-I in the 150-kDa complex. Decreased levels of IGF-I appear to be secondary to increased clearance.

Adolescent↗
PubMed2001

Methotrexate as a possible trigger of macrophage activation syndrome in systemic juvenile idiopathic arthritis.

Macrophage activation syndrome (MAS) is a potentially life threatening complication of chronic rheumatic diseases, particularly systemic juvenile idiopathic arthritis (JIA). A number of triggers have been related to the development of MAS, including viral infections, nonsteroidal antiinflammatory drug therapy, and gold salt injections. We describe a patient with systemic JIA who developed MAS shortly after receiving methotrexate, suggesting that this drug can be regarded as a potential trigger of MAS in children with JIA.

Antirheumatic Agents↗
PubMed2001

Abnormal regulation of interleukin 6 in systemic juvenile idiopathic arthritis.

OBJECTIVE: To evaluate the in vitro production of interleukin 6 (IL-6) by peripheral blood mononuclear cells (PBMC) of patients with systemic juvenile idiopathic arthritis (JIA), its regulation by IL-10, and the association of abnormal regulation of IL-6 production with presence of polymorphisms in the regulatory sequence of the IL-6 gene. METHODS: PBMC were cultured in the absence or presence of lipopolysaccharide (LPS). IL-6 and IL-10 levels were measured by ELISA. Polymorphisms in the regulatory sequences of the IL-6 gene were assessed by restriction fragment length polymorphism analysis and sequencing of amplified regions. RESULTS: Patients' PBMC produced high amounts of IL-6 compared to controls in unstimulated conditions. The IL-10 50% inhibitory dose of LPS stimulated IL-6 production was significantly higher in patients than controls. IL-10 levels produced in the absence or presence of LPS were comparable between patients and controls. The -174 G/C polymorphism in the IL-6 gene does not appear to be correlated with the high unstimulated IL-6 production or with the reduced inhibition by IL-10 observed in patients with JIA. No differences in patients compared to controls and with respect to the published sequence were found in the 3' untranslated region (UTR) of the IL-6 gene. CONCLUSION: Most patients with JIA have increased unstimulated production of IL-6 and reduced inhibition of IL-6 production by IL-10. This abnormal regulation of IL-6 production is not secondary to a defect in IL-10 production, and is not associated with polymorphism of alleles at position -174 of the 5' flanking region or with mutations in the 3' untranslated region of the IL-6 gene.

3' Untranslated Regions↗
PubMed2001

Factors affecting the efficacy of intraarticular corticosteroid injection of knees in juvenile idiopathic arthritis.

OBJECTIVE: To determine in a prospective analysis whether baseline demographic, clinical, and laboratory variables predict the outcome of intraarticular corticosteroid (IAC) injection of the knees in children with juvenile idiopathic arthritis (JIA). METHODS: We studied consecutive patients who met the criteria for the diagnosis of JIA and received their initial injection of triamcinolone hexacetonide in one or both knees. Predictor variables included sex, age, age at onset of JIA, onset subtype, disease duration, drug therapy at the time of IAC injection, physician and parent global assessment of disease status, Childhood Health Assessment Questionnaire disability index, erythrocyte sedimentation rate (ESR), C-reactive protein, involvement of other joints besides knees, amount of fluid aspirated, and dose of IAC injected. The primary outcome measure was persistence of complete clinical response at 6 months, i.e., no evidence of synovitis clinically. RESULTS: Ninety-four patients were available for analysis. At 6 months after the IAC injection, 65 (69%) patients showed a sustained complete clinical response, whereas 29 (31%) had had a recurrence of joint inflammation. Univariate statistical analyses showed that patients who had a sustained clinical response had a significantly higher ESR than those who did not (p = 0.023). The ESR was the only variable that remained in the best-fit model from multivariate logistic regression analysis (OR 2.61, p = 0.049). CONCLUSION: Our findings indicate that patients with JIA who have a higher ESR are more likely to benefit from IAC injection of the knees.

Adrenal Cortex Hormones↗