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Biomedical subjects

S Negri

Publications and source records attributed to S Negri.

At least 19 recordsLinked to original sources

Urinary determination of N-acetyl- S-( N-methylcarbamoyl)cysteine and N-methylformamide in workers exposed to N, N-dimethylformamide.

OBJECTIVES: We conducted this biomonitoring study with the aim of evaluating the correlation between the excretion of N-methylformamide (NMF) (mainly from N-hydroxy- N-methylformamide) and N-acetyl- S-( N-methylcarbamoyl)cysteine (AMCC), and levels of exposure to N, N-dimethylformamide (DMF) among occupationally exposed subjects. METHODS: Exposure levels were determined by personal sampling: breathing zone air samples were collected by means of passive samplers. DMF collected by the charcoal in personal samplers was analysed after extraction with methanol by a gas chromatograph. For the purpose of biological monitoring the levels of NMF and AMCC were measured in pre-shift and post-shift samples. Determinations were carried out by, respectively, gas chromatography and high performance liquid chromatography (HPLC). RESULTS AND CONCLUSIONS: The mean time-weighted average (TWA) exposure was approximately half (13.5 mg/m(3)) of the current threshold limit value, the range of the values was from 0.4 to 75.2 mg/m(3). Environmental DMF concentrations exhibited a significant correlation with the specific mercapturic acid (AMCC) collected at the end of the working week (AMCC Friday morning mg/l=1.384xDMF (mg/m(3))+8.708; r(2)=0.47; P<0.008]; hence urinary AMCC represents an index of the average exposure during several preceding working days, making it possible to calculate the approximate relationship between DMF uptake and excretion of this metabolite. A significant correlation was found also between the daily excretion of NMF and the corresponding levels of DMF in air. The equation of the regression line was: NMF (mg/g creatinine)=0.936xDMF (mg/m(3))+7.306; r(2)=0.522 ( P<0.0001).

Acetylcysteine↗

Cell-permeable peptide inhibitors of JNK: novel blockers of beta-cell death.

Stress conditions and proinflammatory cytokines activate the c-Jun NH2-terminal kinase (JNK), a member of the stress-activated group of mitogen-activated protein kinases (MAPKs). We recently demonstrated that inhibition of JNK signaling with the use of the islet-brain (IB) 1 and 2 proteins prevented interleukin (IL)-1beta-induced pancreatic beta-cell death. Bioactive cell-permeable peptide inhibitors of JNK were engineered by linking the minimal 20-amino acid inhibitory domains of the IB proteins to the 10-amino acid HIV-TAT sequence that rapidly translocates inside cells. Kinase assays indicate that the inhibitors block activation of the transcription factor c-Jun by JNK. Addition of the peptides to the insulin-secreting betaTC-3 cell line results in a marked inhibition of IL-1beta-induced c-jun and c-fos expression. The peptides protect betaTC-3 cells against apoptosis induced by IL-1beta. All-D retro-inverso peptides penetrate cells as efficiently as the L-enantiomers, decrease c-Jun activation by JNK, and remain highly stable inside cells. These latter peptides confer full protection against IL-1beta-induced apoptosis for up to 2 weeks of continual treatment with IL-1beta. These data establish these bioactive cell-permeable peptides as potent pharmacological compounds that decrease intracellular JNK signaling and confer long-term protection to pancreatic beta-cells from IL-1beta-induced apoptosis.

Adaptor Proteins, Signal Transducing↗

Trichloroethylene in urine as biological exposure index.

Occupational exposure to trichloroethylene (TRI) was studied by analysis of environmental air and urine from 49 workers operating in a special printing house on glass. For the measurement of environmental concentration of TRI (Cenv), the ambient air was sampled using personal passive dosimeters. The activated charcoal was desorbed with carbon disulfide and injected into a gas-cromatograph - mass spectrometer (GC-MSD). The biological monitoring of exposed workers was conducted by determining the concentration of TRI in urine (Curine) Urine concentration of TRI was determined by headspace analysis using GC-MSD. Significant correlation was found between the environmental TRI concentration and urinary TRI concentration. The use of a regression equation between Curine (microg/l) and Cenv (mg/m3) (Curine = 0.081 x Cenv + 4.27) resulted in a value of Curine corresponding to Threshold Limit Value-Time Weighted Average (TLV-TWA) exposure value (269 mg/m3) of 26.0 microg/L.

Adult↗

cDNA cloning and mapping of a novel islet-brain/JNK-interacting protein.

IB1/JIP-1 is a scaffold protein that regulates the c-Jun NH(2)-terminal kinase (JNK) signaling pathway, which is activated by environmental stresses and/or by treatment with proinflammatory cytokines including IL-1beta and TNF-alpha. The JNKs play an essential role in many biological processes, including the maturation and differentiation of immune cells and the apoptosis of cell targets of the immune system. IB1 is expressed predominantly in brain and pancreatic beta-cells where it protects cells from proapoptotic programs. Recently, a mutation in the amino-terminus of IB1 was associated with diabetes. A novel isoform, IB2, was cloned and characterized. Overall, both IB1 and IB2 proteins share a very similar organization, with a JNK-binding domain, a Src homology 3 domain, a phosphotyrosine-interacting domain, and polyacidic and polyproline stretches located at similar positions. The IB2 gene (HGMW-approved symbol MAPK8IP2) maps to human chromosome 22q13 and contains 10 coding exons. Northern and RT-PCR analyses indicate that IB2 is expressed in brain and in pancreatic cells, including insulin-secreting cells. IB2 interacts with both JNK and the JNK-kinase MKK7. In addition, ectopic expression of the JNK-binding domain of IB2 decreases IL-1beta-induced pancreatic beta-cell death. These data establish IB2 as a novel scaffold protein that regulates the JNK signaling pathway in brain and pancreatic beta-cells and indicate that IB2 represents a novel candidate gene for diabetes.

Adaptor Proteins, Signal Transducing↗

Electromagnetic interference of bone-anchored hearing aids by cellular phones.

We report a case of electromagnetic interference between a bone-anchored hearing aid (BAHA) and a cellular phone. A 54-year-old women was successfully treated for severe mixed conductive and sensorineural hearing loss with a BAHA. Five years after implantation, the patient experienced a sudden feeling of dizziness, accompanied by a loud buzzing sound and by a sensation of head pressure while examining a digital mobile phone. During a subsequent experiment, the buzzing sound could be reproduced and was identified as electromagnetic interference between the BAHA and digital cellular phones. Seventeen adult BAHA users from our clinic participated in a subsequent survey. Of the 13 patients with some experience of digital cellular phones, 11 reported hearing annoying noises elicited by these devices. However, no other sensation, such as dizziness, was described. Owing to the increasing number of users of both hearing aids and cellular phones, the incidence of electromagnetic interference must be expected to increase as well. Although to date there is no evidence that such interference may be harmful or dangerous to users of conventional or bone-anchored hearing aids, unexpected interference can be a frightening experience.

Electromagnetic Fields↗

[Microcalcifications associated with in situ ductal breast carcinoma. Mammographic and histological correlations with morphometric evaluation].

This study includes 33 cases of ductal carcinoma in situ and its aim is to detect and classify microcalcifications according to their appearance, mammographically, histologically and morphometrically. From the histological point of view, intraductal carcinomas are classified following the criteria proposed by Holland et al. The types of carcinoma examined reveal the presence of different microcalcifications. The calcifications associated with G1 carcinomas appear as highly compact morphometrically, fine or mainly so mammographically and laminated or mixed histologically; no granular calcifications are observed. On the other hand, calcifications associated with type G2 appear as coarse mammographically, granular histologically and scarcely compact morphometrically. Finally, G3 carcinomas mainly reveal by mammography vermicular calcifications (in a few cases associated with fine ones). Granular calcifications are predominant on histological examination while morphometry shows the poorest level of compactness.

Breast Neoplasms↗

Comparison of hydroxyapatite granules to autogenous bone graft in fusion cages in a goat model.

BACKGROUND: With the increased use of fusion cages to achieve lumbar intervertebral fusion, the question arises as to the potential for bone ingrowth from the host bone through the entire cage. Is it even necessary to have an autogenous graft to achieve total bone incorporation? METHODS: Nine adult male goats had fusion cages implanted into three vertebral bodies. The design was Surgical Dynamics/Ray Fusion Cage, measuring 21 mm x 14 mm. In each animal, one fusion cage was filled with autogenous graft, one with hydroxyapatite, porous granules, and the other with nonporous granules. Amount of new bone formation was determined by backscatter electron microscopy at 3 months post implantation in all animals. RESULTS: The histologic section shows that there was total incorporation in all specimens at 3 months. There was slightly more new bone (43%) with the nonporous granules compared with the porous granules (35%). The amount of residual void space was about the same in all specimens, indicating that the amount of new bone formation was similar and not statistically different in cages filled with hydroxyapatite granules versus granules of autogenous bone. CONCLUSION: This study confirms that total incorporation by ingrowth of new bone can be expected in fusion cages. The amount of ingrowth is about the same for autogenous graft versus hydroxyapatite granules. Apparently, it is not necessary to use bone graft to achieve successful bone incorporation if an acceptable biocompatable lattice, such as hydroxyapatite granules, is used.

Animals↗

[Intravascular malignant lymphoma: report of a case].

The authors describe a case of malignant intravascular angiotropic lymphoma presenting an atypical clinical and radiological picture. After postmortem examination, the histologic test performed on various organs showed massive proliferation of mononucleate neoplastic cells inside small and intermediate-sized vessels without involvement of the surrounding parenchyma. The immunohistochemical exams performed permitted the identification of the above-mentioned cells as lymphoid elements belonging to phenotype B. A bilateral papillar renal necrosis was detected. This necrosis, not mentioned by the preceding literature, was, in all probability, caused by alterations of the microcirculation.

Aged↗

Comparison of female geriatric lumbar-extension strength: asymptotic versus chronic low back pain patients and their response to active rehabilitation.

We compared lumbar-extension strength between healthy asymptomatic geriatric females (HEAL) and symptomatic geriatric females (INJ) seeking medical attention for chronic low back pain. The INJ group used the MedX lumbar-extension machine to perform isotonic exercises two times per week and were eventually reduced to one time per week. Range of motion (ROM) and strength were significantly different between groups before beginning the program. After the program, ROM and strength improved significantly and were not different from those of the HEAL group. The average length of treatment was 97 days and 20 visits. Subjective pain ratings were significantly reduced (60%) and exercise weights significantly increased (71%). This reconfirms the notion that many back pain sufferers have weaker lumbar-extension strength and that some symptomatic geriatric women can increase strength with progressive resistance exercise, which leads to a decrease in low back pain.

Aged↗

[Fournier's gangrene: description of a case].

Fournier's gangrene, named after the french dermatologist who was the first to described it in 1883, is a necrotizing fasciitis which affects men's external genitalia and more rarely women's. In most cases the clinical onset is sudden, characterized by fever and local tumefaction rapidly evolving into gangrene. The most credited aetiology is infective and one or more aerobic and/or anaerobic micro-organisms are supposed to be the cause. The pathogenesis involves an endarteritic obliterative process affecting the small vessels of the superficial branch of the internal pudendal artery.

Adult↗

A test to measure lift capacity of physically impaired adults. Part 2--Reactivity in a patient sample.

STUDY DESIGN: Test reactivity is the based on the idea that experience with a test may affect performance on subsequent tests, independent of what the test purports to measure. The reactivity of a test of lift capacity was studied in a single-blind randomized clinical trial was studied in a single-blind randomized clinical trial in which subjects were assigned to one or two groups. One group received lift testing before and after a therapeutic trial, while the other group received lift testing only at the conclusion of the therapeutic trial. OBJECTIVE: To measure the reactivity of a lift capacity test over the course of treatment. SUMMARY OF BACKGROUND DATA: The reactivity of a test is an important criterion by which an outcome measure must be judged. Change in response to treatment is assumed to be independent of changes resulting from the evaluee's experience with the test, although this is rarely addressed. METHODS: The EPIC Lift Capacity test was administered to 55 patients with low back pain in a treatment program after they were randomized into a pre-test/post-test and a post-test only group. Additional measures were taken on a pre-test/post-test basis for all subjects. RESULTS: Analyses of variance demonstrated no difference between the randomized groups after treatment. However, the pre-test/post-test group demonstrated significant improvement over the course of treatment. Other measures of outcome were similarly affected. CONCLUSION: The reactivity of the EPIC Lift Capacity test was negligible over an 8-week treatment regimen that did not include lifting tasks.

Adult↗

Fine needle aspiration of myofibroblastoma of the breast. Case report.

The cytologic and histologic findings of myofibroblastoma of a man's breast are reported. Cytologic specimens showed many scarcely cohesive clusters of bipolar or stellate cells. The cytoplasm was moderately eosinophilic and had clearly-defined edges. The nucleus was characterized by round or coffee-bean shape, regular chromatin and small nucleolus. Atypical features were absent. Immunocytochemical tests confirmed the mesenchymal nature of the lesion showing negativity for CAM 5.2 and positivity for vimentin. We stress the value of fine-needle aspiration biopsy in association with clinical- examination, mammography and/or echography in establishing the preoperative diagnosis of this benign tumor.

Aged↗

Preoperative diagnostic accuracy of fine-needle aspiration in the management of breast lesions: comparison of specificity and sensitivity with clinical examination, mammography, echography, and thermography in 249 patients.

Two hundred and forty-nine women suffering from breast problems underwent a complete series of tests including clinical examination, mammography, echography, thermography, and fine-needle aspiration (FNA). Ninety-four of these patients were shown to be positive or to have suspected malignancy. Accordingly, they underwent surgical excision followed by histologic examination, while the remaining patients were re-examined after 12 to 18 mo in order to exclude false negatives. The analysis of specificity and sensitivity of every single procedure showed that FNA describes the best degree of sensitivity and specificity but no procedure allows, by itself, the detection of all carcinomas. When considered in combination, clinical examination, mammography, and fine-needle aspiration have a sensitivity of 100% and a specificity of 49%, and are the best diagnostic tests for a correct assessment of mammary lesions. Thermography and echography showed a low degree of sensitivity and should not be included in the routine diagnostic procedure of breast lesions.

Biopsy, Needle↗

Immunoreactivity of apo B towards monoclonal antibodies that inhibit the LDL-receptor interaction: effects of LDL oxidation.

We studied the immunochemical stability of the epitopes for six monoclonal antibodies to human apolipoprotein B-100 upon Cu(2+)-mediated (20 microM) oxidation of LDL. The antibodies used in this study, some of which are known to interfere with the interaction of LDL with their cellular receptors, recognize epitopes in the amino terminal region (Mb 19), in the middle part (6B, 2A, 7A, and 9A) and near aa 3500 (Mb 47) of native apo B. All antibodies except one (7A) recognized native and oxidized LDL (OxLDL) equally well; the immunoreactivity of the epitope for Ab 7A was markedly reduced upon LDL oxidation. Since antibodies 2A, 7A, 9A, and Mb 47 inhibit the LDL-receptor interaction and OxLDL poorly interact in vitro with the LDL receptor we conclude that: (1) various epitopes for monoclonal antibodies against native apo B are spared upon LDL oxidation; and (2) the epitopes for antibodies 2A, 9A, and Mb 47 do not define a unique domain of apo B directly involved in the binding of LDL to their receptor.

Antibodies, Monoclonal↗

Defective catabolism of oxidized LDL by J774 murine macrophages.

In J774 murine macrophages, chemically oxidized LDL (OxLDL) and biologically oxidized LDL (BioOxLDL) have similar metabolic fates, characterized by a relatively poor degradation when compared with acetylated LDL (AcLDL), and a modest ability to activate acyl-CoA:cholesterol acyltransferase (ACAT) (850 and 754 pmol [14C]oleate/mg cell protein in OxLDL- and BioOxLDL-incubated cells, versus 425 and 7070 pmol [14C]cholesteryl oleate/mg cell protein in control and AcLDL-incubated cells) with a massive increase of cellular free cholesterol. Therefore, OxLDL were used to investigate the cellular processing of oxidatively modified LDL. Binding and fluorescence microscopy studies demonstrated that OxLDL are effectively bound and internalized by macrophages and accumulate in organelles with density properties similar to those of endo/lysosomes. Although the overall metabolism of OxLDL is modestly affected by 100 microM chloroquine, owing to the poor cellular degradation of the substrate, the drug can further depress OxLDL degradation, indicating that this process takes place in an acidic compartment. Failure to detect products of extensive degradation of OxLDL in the medium is due to their relative resistance to enzymatic hydrolysis, as demonstrated also by in vitro experiments with partially purified lysosomal enzymes, rather than to the intracellular accumulation of degradation products (degraded intracellular protein is, at most, 8.5% of total). This sluggish degradation process is not due to a cytotoxic effect since OxLDL do not affect the intracellular processing of other ligands like AcLDL or IgG. The accumulation of OxLDL-derived products within macrophages may elicit cellular responses, the relevance of which in the atherosclerotic process remains to be addressed.

Animals↗