Fluorescence Image Analyzer - FLIMA: software for quantitative analysis of fluorescence in situ hybridization.

The Fluorescence Image Analyzer (FLIMA) software was developed for the quantitative analysis of images generated by fluorescence in situ hybridization (FISH). Currently, the images of FISH are examined without a coefficient that enables a comparison between them. Through GD Graphics Library, the FLIMA software calculates the amount of pixels on image and recognizes each present color. The coefficient generated by the algorithm shows the percentage of marks (probes) hybridized on the chromosomes. This software can be used for any type of image generated by a fluorescence microscope and is able to quantify digoxigenin probes exhibiting a red color, biotin probes exhibiting a green color, and double-FISH probes (digoxigenin and biotin used together), where the white color is displayed.

Asthma and rhinitis have different genetic profiles for IL13, IL17A and GSTP1 polymorphisms.

BACKGROUND: Asthma and rhinitis have a complex etiology, depending on multiple genetic and environmental risk factors. An increasing number of susceptibility genes are currently being identified, but the majority of reported associations have not been consistently replicated across populations of different genetic backgrounds. PURPOSE: To evaluate whether polymorphisms of IL4R (rs1805015), IL13 (rs20541), IL17A (rs2275913) and GSTP1 (rs1695) genes are associated with rhinitis and/or asthma in adults of Portuguese ancestry. METHODS: 192 unrelated healthy individuals and 232 patients, 83 with rhinitis and 149 with asthma, were studied. All polymorphisms were detected by real time polymerase chain reaction (PCR) using TaqMan assays. RESULTS: Comparing to controls, significant association with asthma was observed for GSTP1 rs1695 AA genotype (odds ratio (OR) - 1.96; 95% CI - 1.18 to 3.25; p=0.010). The association sustains for allergic asthma (OR - 2.17; 95% CI - 1.23 to 3.80; p=0.007). IL13 rs20541 GG genotype was associated with less susceptibility to asthma (OR - 0.55, 95% CI - 0.33 to 0.94, p=0.028). Among patients, IL17A rs2275913 AA genotype was less associated with asthma than with rhinitis (OR - 0.20; 95% CI of 0.07 to 0.56; p=0.002). A similar association was found for IL13 rs20541 GG genotype (OR - 0.48; 95% CI of 0.25 to 0.93; p=0.031). There were no significant differences in the distribution of allelic and genotypic frequencies between patients and controls for the IL4R polymorphism' analyzed. CONCLUSION: These results support the existence of a significant association between GSTP1 rs1695 and IL13 rs20541 SNPs, with susceptibility to asthma, in the population studied. Different genotype profiles of IL17A and IL13 genes seem to influence the clinical pattern of disease expression mainly confined to the upper airways, as rhinitis, or including the lower airways, as asthma.

Determinantes de lucratividade em fazendas leiteiras de Minas Gerais / Determinants of profitability in Minas Gerais dairy farms

Identificaram-se quais indicadores de desempenho determinam a variação na lucratividade de 159 fazendas da região Triângulo Mineiro-Alto Paranaíba de Minas Gerais. A lucratividade foi mensurada pela renda líquida anual (RL), RL sobre o valor dos bens e RL sobre a renda bruta. Cento e dezenove fazendas com lucratividade positiva produziram mais leite por mão de obra e por vaca, tinham maior proporção de vacas em lactação e maior proporção de custo com concentrados, custo com mão de obra com menor proporção do custo de produção e menor relação entre o custo com mão de obra e o custo com concentrados do que as 40 fazendas com lucratividade negativa (P<0,01). A análise de componentes principais mostrou que os principais determinantes da variação na lucratividade entre fazendas foram: relação entre o custo com mão de obra e o com concentrados, custo de mão de obra por litro de leite, produção de leite por mão de obra, produção de leite por vaca e proporção de vacas lactantes no rebanho. Maior lucratividade foi associada ao uso mais eficiente da mão de obra, ao maior investimento em concentrados e ao ganho na produção por vaca.(AU)

We identified which performance indicators determined the variation in profitability of 159 farms of the Triângulo Mineiro-Alto Paranaíba region of Minas Gerais. Profitability was measured by annual net income (RL), RL over assets value, and RL over gross income. The 119 farms with positive profitability produced more milk per labor and per cow, had a greater proportion of lactating cows in the herd, had concentrates cost as a greater proportion and labor cost as a smaller proportion of the production cost, and had smaller ratio of labor cost to concentrates cost than the 40 farms with negative profitability (P<0.01). Principal component analysis showed that the key determinants of profitability variation among farms were: The ratio of labor cost to concentrates cost, labor cost per liter of milk, milk yield per labor, milk yield per cow, and the proportion of lactating cows in the herd. Increased profitability was associated with more efficient labor usage, the result of larger investment in concentrates and greater yield per cow.(AU)

Indicadores de desempenho de fazendas leiteiras de Minas Gerais / Performance indicators of Minas Gerais dairy farms

Foram avaliados indicadores de desempenho de 159 fazendas de leite da região Triângulo Mineiro-Alto Paranaíba no estado de Minas Gerais, em 2007 e 2008. Os dados foram obtidos mensalmente por 18 consultores privados. A produção de leite foi de 770(697 L/d, oriunda de 81(54 vacas em lactação, exploradas em 109(75 ha. A produção anual de leite por hectare foi de 3333(2.720 L, oriunda de 0,70(0,44 vacas em lactação/ha, por vaca adulta foi de 3383(1.269 L, e 26(8% do rebanho adulto era não lactante. A produção de leite por mão-de-obra contratada foi 103342(44616 L. Concentrados constituíram 30% e mão-de-obra 10% do custo de produção. A renda líquida foi em média positiva, mas o resíduo foi negativo em 15 e 25% das fazendas, quando a estimativa de custo computou ou não os juros sobre o valor dos bens, respectivamente. Os indicadores de lucratividade foram: renda líquida anual R$32841,00; renda líquida anual sobre o valor dos bens 4,7%; e renda líquida sobre a renda bruta 8,7%. Mesmo com desempenho acima das médias brasileira e mineira, os indicadores de desempenho foram modestos, sugerindo existir oportunidade para ganho em eficiências produtiva e financeira.(AU)

Performance indicators of 159 dairy farms in the Triângulo Mineiro-Alto Paranaíba region of the Minas Gerais state, in 2007 and 2008, were evaluated. Data was obtained monthly by 18 private consultants. Milk yield was 770(697 L/d, from 81(54 lactating cows, and 109(75 ha were explored. Yearly milk yield per hectare was 3,333(2,720 L, from 0.70(0.44 lactating cows/ha, per adult cow was 3,383(1,269 L, and 26(8% of the adult herd was non-lactating. Milk yield per hired labor was 103,342(44,616 L. Concentrates cost was 30% and labor 10% of the production cost. The mean net income was positive, but 15 and 25% of the farms had negative residue, when cost was estimated computing or not the interest on assets value, respectively. Profitability indicators were: annual net income R$32,841.00; annual net income over assets value 4.7%; and net income over gross income 8.7%. Even though performance was above Brazilian and Minas Gerais means, performance indicators were modest, suggesting that there is opportunity for gain in productive and financial efficiencies.(AU)

Diagnóstico na infância: quais as implicações possíveis? / Diagnosis of childhood: what are the possible implications?

Este artigo objetivou abordar as especificidades do processo diagnóstico nas psicopatologias na infância apartir de uma revisão da literatura. Num primeiro momento, realizou-se uma fundamentação teóricaacerca de como a psicanálise concebe o diagnóstico, contrapondo com a perspectiva médica.Posteriormente, refletiu-se sobre como pensar esse processo na infância, considerando suasparticularidades. Por fim, discutiram-se as repercussões do ato diagnóstico nesse período tão peculiar,tendo como inspiração recortes da prática em psicologia clínica e escolar, articulando-os com os achadosteóricos. Enfim, discutiu-se sobre a excessiva prescrição medicamentosa percebida na atualidade, comotambém sobre os efeitos possíveis que podem surgir nos espaços por onde a criança circula: seu meiofamiliar, escolar e social(AU)

IRAK1 variant is protective for orthodontic-induced external apical root resorption.

OBJECTIVE: Interleukin-1 beta (IL1B) pathway is a key player in orthodontic-induced external apical root resorption (EARR). The aim of this work was to identify the genes related to the IL1 pathway as possible candidate genes for EARR, which might be included in an integrative predictive model of this complex phenotype. MATERIALS AND METHODS: Using a stepwise multiple linear regression model, 195 patients who had undergone orthodontic treatment were assessed for clinical and genetic factors associated with %EARRmax (maximum %EARR value obtained for each patient). The four maxillary incisors and the two maxillary canines were assessed. Three functional single nucleotide polymorphisms (SNPs) were genotyped: rs1143634 in IL1B gene, rs315952 in IL1RN gene, and rs1059703 in X-linked IRAK1 gene. RESULTS: The model showed that four of the nine clinical variables and one SNP explained 30% of the %EARRmax variability. The most significant unique contributions to the model were gender (P = 0.001), treatment duration (P < 0.001), premolar extractions (P = 0.003), Hyrax appliance (P < 0.001), and homozygosity/hemizygosity for variant C from IRAK1 gene (P = 0.018), which proved to be a protective factor. CONCLUSION: IRAK1 polymorphism is proposed as a protective variant for EARR.

Genetic polymorphisms of phase I and phase II metabolic enzymes as modulators of lung cancer susceptibility.

OBJECTIVES: Tobacco exposure remains the main etiologic factor for lung cancer (LC). Interactions between environment and individual genetic profile are particularly important for this disease. The aim of this study was to evaluate the contribution of CYP1A1*2A, CYP1A1*2C, CYP2D6*4, GSTP1, GSTM1, GSTT1 and NAT2 polymorphisms for the susceptibility to LC in a Portuguese population considering their demographic and clinical characteristics. MATERIALS AND METHODS: A total of 200 LC and 247 controls subjects from the Centre of Portugal were studied. Clinical and demographic characteristics were collected from clinical files and by individual questionnaires. Polymorphisms of CYP1A1*2A, CYP1A1*2C, CYP2D6*4, GSTP1, GSTM1, GSTT1 and NAT2 were genotyped using PCR-RFLP, PCR multiplex, ARMS and real time. RESULTS: Gender, family history of cancer, smoke cessation and alcohol consumption were independent risk factors (p < 0.05). Associations found between phases I and II genes and LC population reveal a sex dependent distribution. Logistic regression analysis demonstrates that enhanced activation by CYPs, associated by reduced or loss of function of phase II enzymes, can lead to a greater risk. GSTP1 and NAT2 polymorphisms studied have a significant contribution for the histological tumour types and the presence of metastases, at time of diagnosis, respectively, when males with smoking habits were considered. CONCLUSION: Multiple interactions between environment and individual characteristics are clearly associated to this disease. Variants of the detoxification genes may act synergistically contributing to this disease and modifying the risk posed by smoking and sex. The GSTT1*0 and GSTP1 (Ile462Val) might contribute to the malignant phenotype through different mechanisms.

Influence of hyperoxia and mechanical ventilation in lung inflammation and diaphragm function in aged versus adult rats.

Although assist ventilation with FIO2 0.21 is the preferable mode of ventilation in the intensive care unit, sometimes controlled ventilation with hyperoxia is needed. But the impact of this setting has not been extensively studied in elderly subjects. We hypothesized that a high fraction of inspired oxygen (FiO(2)) and controlled mechanical ventilation (CMV) is associated with greater deleterious effects in old compared to adult subjects. Adult and old rats were submitted to CMV with low tidal volume (6 ml/kg) and FiO(2) 1 during 3 or 6 h. Arterial blood gas samples were measured at 0, 60 and 180 min (four groups: old and adult rats, 3 or 6 h of CMV), and additionally at 360 min (two groups: old and adult rats, 6 h of CMV). Furthermore, total protein content (TPC) and tumor necrosis factor-alpha (TNF-α) in bronchoalveolar lavage were assessed; lung tissue was used for malondialdehyde and histological analyses, and the diaphragm for measurement of contractile function. Arterial blood gas analysis showed an initial (60 min) greater PaO(2) in elderly versus adult animals; after that time, elderly animals had lowers pH and PaO(2), and greater PaCO(2). After 3 h of CMV, TPC and TNF-α levels were higher in the old compared with the adult group (P < 0.05). After 6 h of MV, malondialdehyde was significantly higher in elderly compared with the adult animals (P < 0.05). Histological analysis showed leukocyte infiltration and edema, greater in old animals. In diaphragm, twitch contraction with caffeine significantly declined after 6 h of CMV only for the elderly group. These data support the hypothesis that relatively short-term CMV with low tidal volume and hyperoxia has greatest impact in elderly rats, decreasing diaphragmatic contractile function and increasing lung inflammation.

Post-polio syndrome: epidemiologic and prognostic aspects in Brazil.

OBJECTIVES: To describe the clinical and epidemiological aspects of post-polio syndrome (PPS) and identify predictors of its severity. MATERIALS AND METHODS: 132 patients with PPS were selected at the Neuromuscular Disease Outpatient Clinic of the Federal University of São Paulo. Descriptive analysis was carried out and predictors of PPS severe forms were investigated using an unconditional logistic regression. RESULTS: The average age at onset was 39.4 years. The most common symptoms were fatigue (87.1%), muscle pain (82.4%) and joint pain (72.0%); 50.4% of the cases were severe. The following were associated with PPS severity: a < or =4-year period of neurological recovery (OR 2.8), permanent damage in two limbs (OR 3.6) and residence at the time of acute polio in a city with more advanced medical assistance (OR 2.5). CONCLUSIONS: Health professionals should carefully evaluate polio survivors for PPS and be aware of the implications of muscle overuse in the neurological recovery period.

Endectocide activity of a new long-action formulation containing 2.25% ivermectin+1.25% abamectin in cattle.

The present work aimed to evaluate the endectocide activity of a new injectable long-action formulation, containing ivermectin (IVM) and abamectin (ABA). In each one of the four experiments performed, the following groups were formed: group I: 2.25% IVM (450 microg/kg)+1.25% ABA (250 microg/kg), group II: 3.15% IVM (630 microg/kg) and group III: control. Eighteen bovine naturally infected by gastrointestinal nematoda were selected for anthelmintic evaluation and necropsied on posttreatment day (PTD) 14 to estimate the total parasitic burden. For the Rhipicephalus (Boophilus) microplus field trial, 30 bovine were selected by means of counts of semi-engorged R. (B.) microplus and the therapeutic and residual efficacy evaluated by tick counts on PTDs 1, 3, 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 77, 84 and 91. In the stall test, 15 calves were artificially infested with 5000 R. (B.) microplus (Mozzo strain) larvae three times a week and daily collections of all the engorged female ticks detached from each calf were performed until the PTD 80. Forty bovine naturally infected with Dermatobia hominis larvae were selected and the number of larvae was counted by visual and tactile inspection on PTDs 3, 7, 14, 28, 35, 49, 63, 77, 91 and 105. In this trial, a formulation containing 1% doramectin (200 microg/kg) was also used. IVM+ABA formulation and 3.15% IVM eliminated four of the eight species of nematode identified. The anthelmintic efficacy of the avermectins association against Haemonchus placei, Cooperia spatulata and C. punctata was 89.64%, 98.84% and 97.69%, while 3.15% IVM achieved 30.98%, 84.79% and 75.56%, respectively. The two formulations evaluated showed reduced acaricide action on the PTD 1 and 3, reaching high efficacy percentages from PTD 14 onward. The IVM+ABA showed efficacy above 95% in the period between PTDs 21 and 49. In the stall test, it observed no difference (P>0.05) between the two formulations regarding the R. (B.) microplus counts during the entire evaluation period. IVM+ABA reduced the number of ticks from the PTD 1 to 77 (P<0.05) and 3.15% IVM reduced (P<0.05) the tick number from PTD 4 up to PTD 80. The three endectocides showed no difference (P>0.05) regarding the number of D. hominis larvae and prevented this parasite reestablishment until PTD 105. These results indicate that the IVM+ABA association showed higher anthelmintic activity and similar efficacy against arthropods to the formulation containing 3.15% IVM.

Soluble VCAM-1 and E-selectin in breast cancer: relationship with staging and with the detection of circulating cancer cells.

In breast cancer, the correct evaluation of cancer dissemination is essential to establish prognosis and treatment choices. This study analyses the relationship between circulating levels of soluble VCAM-1 and E-selectin and the presence of circulating cancer cells in breast cancer patients. Plasma levels of VCAM-1 and E-selectin were measured by enzyme-linked immunosorbent assay (ELISA). The presence of circulating cancer cells was diagnosed using a RT nested-PCR assay detecting the cancer specific transcript, epidermal growth factor receptor variant III (EGFRvIII) mRNA. Blood samples were collected from 64 patients divided in three groups: group A of 11 women selected for neoadjuvant chemotherapy; group B of 13 women with metastatic disease and group C, with 40 women having completed their treatment at least one year ago and with no evidence of relapse. The mutant transcript was detected in 45.5% of patients from group A, in 61.5% of patients from group B and in none of the group C patients. For both VCAM-1 and E-selectin, plasma levels increased with disease staging and with the presence of EGFRvIII mRNAin peripheral blood. The differences were statistically significant (p < 0.025) when group C was compared with all patients from group B, with patients from group B with EGFRvIII positive results or with all patients with EGFRvIII positive results. Increased plasma levels of VCAM-1 and E-selectin are associated with advanced stage of breast cancer and with the presence of circulating cancer cells. The combined analysis of these parameters may contribute to a more accurate evaluation of cancer dissemination.

Tangential-flow ultrafiltration: a versatile methodology for determination of complexation parameters in refractory organic matter from Brazilian water and soil samples.

In this work the copper(II) complexation parameters of aquatic organic matter, aquatic and soil humic substances from Brazilian were determined using a new versatile approach based on a single-stage tangential-flow ultrafiltration (TF-UF) technique (cut-off 1 kDa) and sensitive atomic spectrometry methods. The results regarding the copper(II) complexation capacity and conditional stability constants obtained for humic materials were compared with those obtained using direct potentiometry with a copper-ion-selective electrode. The analytical procedure based on ultrafiltration is a good alternative to determine the complexation parameters in natural organic material from aquatic and soil systems. This approach presents additional advantages such as better sensibility, applicability for multi-element capability, and its possible to be used under natural conditions when compared with the traditional ion-selective electrode.

Non-malignant asbestos-related diseases in Brazilian asbestos-cement workers.

BACKGROUND: Production of asbestos-cement products in Brazil started in the 1940s, peaked in the 60-70s and is still an active industry. This study was designed to assess the non-malignant effects of asbestos exposure in the asbestos-cement industry in Brazil. METHODS: A group of 828 former asbestos-cement workers enrolled in a cross-sectional and cohort study of respiratory morbidity, submitted to a detailed occupational history, respiratory symptoms questionnaire, spirometry, PA chest x-ray, and high resolution computed chest tomography (HRCT). Asbestos exposure was assessed by years of exposure, cumulative exposure (a semi-quantitative method), and latency time from first exposure. Asbestosis and pleural thickening were assessed according to HRCT criteria. RESULTS: Asbestosis was present in 74 (8.9%) and pleural thickening in 246 (29.7%). Using the HRCT as the "best available evidence", it was shown that were more false negatives than false positives in the x-ray readings for parenchymal (21.6% false negatives, 4.2% false positives) and pleural (26.0% false negatives, 14.4% false positives) diseases due to asbestos. Latency time from first exposure was the best predictor for both asbestosis and pleural thickening. Subjects in the higher exposure groups presented lower levels of lung function. Obstructive defects were significantly related to smoking, shortness of breath, body mass index, and age, whereas restrictive defects were related to asbestosis, shortness of breath, and latency time. Chronic bronchitis increased with latency time in the three smoking groups and was significantly related to pleural thickening (OR 1.56 (1.00-2.42)). Shortness of breath was significantly associated with body mass index and pleural thickening (OR 1.30 (1.24-2.09)). CONCLUSIONS: Pleural thickening and asbestosis showed a significant association with latency time and exposure. FVC and FEV(1) decreased across increasing profusion with an added effect of pleural thickening. There was a significant and independent effect of exposure on lower levels of FVC and FEV(1). Obstructive defects were mainly related to smoking and restriction to asbestosis. Dust exposure and smoking were synergistic in increasing chronic bronchitis and shortness of breath report. Shortness of breath report was also related to pleural thickening and higher body mass index.

The effect of cyclosporin A on the activity of matrix metalloproteinases during the healing of rat molar extraction wounds.

Cyclosporin A (CyA) is a cyclic peptide used as an immunosuppressive agent because it can block the synthesis of interleukin-2 and other cytokines produced by CD4+ lymphocytes. It is widely used for the prevention of allograft rejection and treatment of autoimmune diseases. Several side-effects of CyA treatment have been reported, among which are chronic nephrotoxicity, hepatotoxicity and neurotoxicity, lymphoproliferative neoplasms, hypertension, thromboembolic complications and gingival overgrowth. Here, using a rat molar model, it is demonstrated that CyA immunosuppression inhibits the activity of matrix metalloproteinases 2 and 9 in the early phase of granulation tissue in the healing dental socket. These observations suggest that CyA may interfere with the wound healing following dental extractions.

[Malignant hyperthermia susceptibility in 3 patients with malignant neuroleptic syndrome]. / Susceptibilidade à hipertermia maligna em três pacientes com síndrome maligna por neurolépticos.

Hyperthermia, skeletal muscle rigidity, rhabdomyolysis, acidosis and multiple system insufficiency characterize malignant hyperthermia. Anaesthetic malignant hyperthermia follows halogenated volatile agents and/or depolarizing muscle relaxants utilization. Diagnosis is based on in vitro muscle contracture in response to halothane and/or caffeine exposure. Neuroleptic malignant syndrome affects patients taking neuroleptic drugs; clinical findings include hyperthermia, extrapyramidal rigidity, acidosis, neurovegetative instability and neurological signs. We report three neuroleptic malignant syndrome patients with positive muscle contracture tests which shows that muscle from neuroleptic malignant syndrome patients may in some instances show alterations similar to those of anaesthetic malignant hyperthermia.

Does the A3333G mutation in the CACNL1A3 gene, detected in malignant hyperthermia, also occur in central core disease?

Malignant hyperthermia (MH) and central core disease (CCD) are two conditions associated with susceptibility to volatile anesthetics and depolarizing muscle relaxants. The gene RYR1, encoding the Ca2+ release channel of skeletal muscle sarcoplasmic reticulum, is responsible for about 50% of the cases of MH and some cases of CCD. However, genetic heterogeneity occurs in MH and a mutation in a second gene (CACLN1A3), encoding the alpha1-subunit of the dihydropyridine (DHP) channel, has recently been found in a large MH French family. The presence of this mutation in patients with CCD has not yet been reported. In this study, we analyzed the A3333G mutation in 5 unrelated patients affected by CCD and 31 MH-susceptible relatives (from 19 MH families) and did not find this mutation in any of them. Nevertheless, the report of data on newly described mutations in different populations is important to estimate the contributions of each gene mutation to the phenotype of MH and CCD.

Asbestos-Related Pleural Thickening is Independently Associated With Lower Levels of Lung Function and with Shortness of Breath.

This study investigated the relative contribution of asbestos-related pleural thickening (PT) to lung function indices and to respiratory symptoms. A group of 828 former asbestos cement workers enrolled in a cross-sectional and cohort study of respiratory morbidity and submitted to a detailed occupational history, respiratory symptoms questionnaire, spirometry, postero-anterior chest x-ray, and high-resolution computed chest tomography (HRCT). Asbestos exposure was assessed by years of exposure (a semi-quantitative method), cumulative exposure, and latency time from first exposure. Smoking was assessed in pack-years. PT and asbestosis were assessed according to HRCT criteria. Statistical analysis included descriptive analysis, univariate and multivariate analysis of variance for comparisons of factors related to PT, stepwise multiple regression analysis for continuous dependent variables, and logistic regression analysis for dichotomous dependent variables. Mean age was 51.4 (SD 10.5) years, mean years of exposure 12.4 (SD 8.8), mean cumulative exposure 79.9 (SD 68.5), and mean latency time 25.2 yr (SD 10.4). Of the 828, 238 (28.7%) were smokers, 288 (34.8%) former smokers, and 302 (36.2%) nonsmokers. PT was present in 246 (29.7%) and asbestosis in 74 (8.9%); 97 (11.9%) had shortness of breath of Grade III or more. PT subjects had lower height-adjusted forced vital capacity (FVC) and forced expiratory volume in I s (FEV1) and lower FEV1/FVC% (p < .00001 for all). Variables significantly related to PT were age (p < .000 1), years of exposure (p < .0000 1), cumulative exposure (p < .00001), latency time (p < .00001), pack-years (p < .0000 1), and asbestosis (p < .00 1). In a multiple stepwise regression model, after controlling for confounders, height adjusted FEV1 and FVC were in versely and significantly associated with PT, mainly when associated with asbestosis. A logistic regression model with shortness of brea th as the dependent va riable, con trolled for confounders, showed that PT was significa ntly associated with the symptom, even without asbestosis. In conclusion, PT is independently associated with lower va lues of FEV1 and FVC. PT is also independently associated with an increased risk of shortn ess of breath report. PT should be considered as a disease for clinical follow up and for compensa tion claims.

Therapeutic resistance: characterization and inactivation by specific antiserum of a putative protein family produced by tumour cells.

A multitherapy resistance (MTR) factor produced by Cloudman S91 mouse melanoma cells rescues a responsive cell line after gamma-irradiation, short wavelength ultraviolet light, mitomycin C, vinblastine and actinomycin D. A similar activity with respect to ionizing radiation is now shown to be produced by human melanoma cells and by both human and mouse breast cancer cells but not by five normal cell lines. In these studies, the factor produced in serum-free conditioned medium (SFCM) by Cloudman S91/I3 cells is further characterized. Its activity in a clonogenic assay using related Cloudman S91/amel cells is destroyed by trypsin but not by DNase and is stable for at least 8 days at a variety of temperatures including 37 degrees C. Molecules greater than 30 kDa from SFCM collected from S91/I3 cells were concentrated and separated by preparative zonal electrophoresis (PZE). Bioactivity was present in both the cathode- and the anode-running fractions. The active acidic (anode) fractions were analysed by preparative isoelectric focusing. Bioactivity was present between pI 3.5 and 4.2. These PZE fractions were also used to immunize two rabbits, both of which produced antiserum that abrogated the bioactivity of SFCM and of the PZE cathode fractions. Antiserum also decreased the survival of irradiated S91/I3 producer cells that do not respond to SFCM but nonetheless must require MTR proteins for the expression of radiation resistance. These studies present a model for the production of rescue factors by non-clonogenic tumour cells that may persist in some tumours for considerable periods of time.

Magnetic resonance imaging in five patients with a tumefactive demyelinating lesion in the central nervous system.

Five patients with a tumefactive lesion were clinically followed from 1992 to 1993. Four patients were female; age ranged from 32 to 57 years, the duration of symptoms varied from 3 days to 3 years. Neurological examination disclosed dementia in two patients, aphasia in three, hemiparesis in four, hemihypoaesthesia in three, optical neuritis in two, tetraparesis with sensitive level and neurogenic bladder in one. MRI disclosed lesions with a hypersignal on images assessed at T2 and hyposignal at T1, and gadolinium heterogeneous enhancement; these lesions were located in the: a) temporooccipital region bilaterally and brain stem, b) frontoparietal white matter, c) basal ganglia, bilateral white matter and brain stem, d) left parietal region, e) cervical spinal cord, with enlargement of this region. Cerebral biopsy was performed in three patients; acute and subacute demyelinating disease was diagnosed by histological examination. Two patients had an evolutive diagnosis; exclusion of other pathologies and clinical and radiological improvement after corticotherapy, pointed to an inflammatory disease.