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This work presents the first simultaneous X‐ray measurement and high‐speed video observation of the propagation of a lightning leader producing X‐rays. As a result, the three‐dimensional leader distance from the X‐ray measurement and, for the first time, the conditions of the preexisting channel during the leader propagation were observed. Although four leaders in this seven‐stroke flash followed the same path to ground, X‐rays were only observed during the leader before the return stroke with the highest peak current. The fact that the other three leaders following the same path to ground did not produce detectable X‐rays confirms the hypothesis that leader line charge density is an important factor that determines X‐ray production. The fact that X‐rays was recorded only when the leader tip was at a certain portion of the lightning channel confirms that the orientation of the leader plays an important role in the detection of X‐rays. Plain Language Summary: It was known that lightning can produce X‐rays. However, in this study, thanks to the use of a high‐speed video camera it was possible to determine when lightning produces X‐rays, how far it was, how it was oriented when the detection of X‐rays, and what the conditions of the preexisting channel were during the leader propagation. The observations of the present work allow for new insights, confirmation of some hypotheses, and comparison with past studies. The results presented help to understand why X‐rays are sometimes detected and sometimes not. It is shown that the amount of charge transferred by the discharge plays a crucial role. This study also confirms that the orientation of the descending leader plays an important role in the detection of X‐rays. Key Points: First high‐speed video observation of a natural lightning leader producing X‐rays during its propagation to groundExperimental confirmation that the production of X‐rays depends on the leader charge density in natural lightningThe orientation of the leader plays an important role in the detection of X‐rays [ABSTRACT FROM AUTHOR]

I Editor i Serology for anti-epidermal transglutaminase antibodies (Anti-TG3 Abs) has attracted interest, being inexpensive and non-invasive and could ideally replace skin biopsy for the diagnosis of Dermatitis Herpetiformis (DH).1 The current commercially available ELISA (Elisa kit) for serum Anti-TG3 Abs overall has a good specificity (84-100%)2-4; however, its clinical use is limited due to variable sensitivity (45-100%) and low specificity in Coeliac Disease (CD) patients (47-85%) in whom Anti-TG3 Abs may be present in the absence of DH.2,3,5-7 Here, we developed and evaluated the diagnostic performance of a novel ELISA to quantitatively measure Anti-TG3 Abs. Interestingly, the specificity of the novel ELISA varied when considering CD patients by age and was higher in patients <=25 years (specificity 97%) versus patients >25 years (specificity 55%). [Extracted from the article]

Abstract: Background: Extremely low birth weight (ELBW; <1,000 g) infants are the most vulnerable babies and are at higher risk for experiencing overprotective (i.e., controlling and intrusive) parenting, which is hypothesized to contribute to the risk for mental disorders. Despite the increased risk for anxiety disorders and decreased risk for alcohol or substance use disorders seen in ELBW survivors, no research has examined the impact of parenting. This study investigated if overprotective parenting mediates links between ELBW birth status and psychiatric disorders in adulthood. Study design: Participants included ELBW survivors born in 1977–1982 and matched normal birth weight (≥2,500 g) control participants (ELBW n = 81; normal birth weight n = 87) prospectively followed in Ontario, Canada. These individuals retrospectively reported on whether either of their parents was overprotective using the Parental Bonding Instrument. Presence of a current anxiety disorder and of current alcohol or substance use disorders was assessed using the Mini International Neuropsychiatric Interview at age 29–36 years. Results: Path analysis showed that overprotective parenting was a significant mediator of the association between ELBW status and risk for an anxiety disorder in adulthood and the risk for an alcohol or substance use disorder in adulthood in ELBW survivors. Overprotective parenting accounted for 53% of the association between ELBW status and the risk for an anxiety disorder in adulthood and 26% of the association between ELBW status and alcohol or substance use disorders. Conclusions: Overprotective parenting accounted for a substantial proportion of the increased risk for anxiety and alcohol or substance use disorders in adulthood in ELBW survivors. Despite their perceived vulnerabilities, it is important that the parents of ELBW survivors be supported in their attempts to facilitate their children's pursuit of independence during childhood and beyond. [ABSTRACT FROM AUTHOR]

We present the leaf and floral transcriptomes of two hybridizing bromeliad species that differ in their major pollinator systems. Here we identified candidate genes responsible for pollinator attraction and reproductive isolation in these two species. We searched for candidate genes involved in floral traits, such as colour. Approximately 34 Gbp of cDNA sequence data were produced from both tissues and species, resulting in a total of 424 506 914 raw reads. The de novo-assembled transcriptomes consisted of a total of 263 955 contigs, further clustered into 110 977 unigenes. Over 58% of the unigenes were functionally annotated and assigned to one or more Gene Ontology terms. The transcriptomes revealed 144 unique transcripts that encode key enzymes in the flavonoid and anthocyanin biosynthesis pathways. The domain/family annotation and phylogenetic analysis allowed us to infer, by homology, potential functions of the genes encoding MYB, HD- ZIP and bZIP- HY5 transcription factors, as well as WD40 protein, which may be involved in anthocyanin and flavonoid regulation in these species. These candidate genes are associated with natural regulation in flower colour in other plant species and will facilitate future studies aimed at elucidating the molecular basis of adaptive differentiation and the evolution of mechanisms of pollinator-mediated reproductive isolation in these two bromeliads. In addition, we identified a total of 49 439 microsatellite loci. These resources will assist future research into adaptation and speciation events in bromeliad species, thus providing a starting point for investigation of the molecular mechanisms of the traits responsible for their reproductive isolation. [ABSTRACT FROM AUTHOR]

Xanthomonas citri subsp . citri (Xcc) is the causal agent of citrus canker, a disease that affects almost all types of citrus crops. Production of particular Xcc pathogenicity factors is controlled by a gene cluster rpf, which encodes elements of a cell-cell communication system called quorum sensing ( QS), mediated by molecules of the diffusible signal factor ( DSF) family. Interference with cell-cell signalling, also termed quorum quenching, either by signal degradation or over-production, has been suggested as a strategy to control bacterial disease. In this study, three bacterial strains were isolated from citrus leaves that displayed the ability to disrupt QS signalling in Xcc. Pathogenicity assays in sweet orange ( Citrus sinensis) showed that bacteria of the genera Pseudomonas and Bacillus also have a strong ability to reduce the severity of citrus canker disease. These effects were associated with alteration in bacterial attachment and biofilm formation, factors that are known to contribute to Xcc virulence. These quorum-quenching bacteria may represent a highly valuable tool in the process of biological control and offer an alternative to the traditional copper treatment currently used to treat citrus canker disease. [ABSTRACT FROM AUTHOR]

Background Adolescents with food allergy have poorer psychosocial outcomes compared with their nonallergic counterparts; however, few studies have prospectively examined the mental health of adolescents and young adults in this vulnerable population. Our objectives were to estimate the prevalence of emotional and behavioral problems in an epidemiological sample of adolescents and young adults with food allergy; determine whether food allergy is associated with adolescent and maternal reports of such problems; and examine the patterns of change in emotional and behavioral problems from adolescence to young adulthood among individuals with and without food allergy. Methods Data came from 1303 participants at 14 and 21 years of age in the Mater University Study of Pregnancy. Emotional and behavioral problems were measured using self- and maternal-reported symptoms of depression, anxiety, attention/deficit hyperactivity disorder (ADHD), oppositional defiant disorder, and conduct disorder. Results Maternal, but not self-reports suggested that emotional and behavioral problems were higher among adolescents with food allergy. Food allergy was associated with increased odds of elevated levels of maternal-reported symptoms of depression [OR = 4.50 (1.83, 11.07)], anxiety [OR = 2.68 (1.12, 6.44)], and ADHD [OR = 3.14 (1.07, 9.19)] in adolescence. Food allergy was also associated with depressive symptoms that persisted from adolescence to young adulthood [OR = 2.05 (1.04, 4.03)]. Conclusions Emotional and behavioral problems, particularly symptoms of depression, anxiety, and ADHD, are common among adolescents with food allergy in the general population and, in the case of elevated levels of depressive symptoms, persist into young adulthood. Healthcare professionals should seek adolescent and parental perspectives when assessing emotional and behavioral problems and monitor mental health during the transition to adulthood. [ABSTRACT FROM AUTHOR]

Objective To evaluate the environmental and ecological factors associated with Leishmania transmission and vector abundance in Chaparral, Tolima-Colombia. Methods First, we compared the ecological characteristics, abundance of phlebotomies and potential reservoir hosts in the peridomestic environment (100 m radius) of randomly selected houses, between two townships with high and low cutaneous leishmaniasis incidence. Second, we examined peridomestic correlates of phlebotomine abundance in all 43 houses in the higher risk township. Results The high transmission township had higher coverage of forest (23% vs. 8.4%) and shade coffee (30.7% vs. 11%), and less coffee monoculture (16.8% vs. 26.2%) and pasture (6.3% vs. 12.3%), compared to the low transmission township. Lutzomyia were more abundant in the high transmission township 2.5 vs. 0.2/trap/night. Lutzomyia longiflocosa was the most common species in both townships: 1021/1450 (70%) and 39/80 (49%). Numbers of potential wild mammal reservoirs were small, although four species were found to be infected with Leishmania ( Viannia) spp. In the high transmission township, the overall peridomiciliary capture rate of L. longiflocosa was 1.5/trap/night, and the abundance was higher in houses located nearer to forest (ρ = −0.30, P = 0.05). Conclusion The findings are consistent with a domestic transmission cycle with the phlebotomies dependent on dense vegetation near the house. [ABSTRACT FROM AUTHOR]

Cardiac screening is recommended to prevent cardiovascular death after renal transplantation. This retrospective observational study illustrates the results of application of a cardiac assessment algorithm in a series of 558 renal transplant candidates at a single center in Turin, Italy. A dipyridamole-stress sestamibi myocardial scintiscan (DMS) performed in 302/558 (54.1%) cases was positive in 52 (17.2%), negative in 200 (66.2%), borderline in 16 (5.3%), and with signs of previous necrosis in 34 (11.4%). Coronary lesions detected by angiography in 48.1% of the 52 positives were treated medically (13.5%) or by percutaneous/surgical procedure (34.6%). Coronary lesions were detected in 14.1% of asymptomatic population subgroup. The minor and major cardiovascular event rates and the cardiovascular death rate were 1.9%, 0%, and 0%, respectively, in positive DMS group (high-cardiological risk) vs. 10%, 4.5%, and 3.5% in the negatives (p > 0.5; n.s.). It is suggested that not increased cardiovascular event or deaths rates in the high-risk group reflect early coronary lesion detection and correction. Since 55.9% of cardiovascular events or deaths occurred in the negative group more than 24 months after the DMS, its mandatory repetition every two yr after a negative finding is recommended. [ABSTRACT FROM AUTHOR]

The advent of globalization has changed our perspectives radically. It presents increased understanding of world affairs, new challenges and exciting opportunities. The inequitable distribution and use of finite energy resources and global warming are just two examples of challenges that can only be addressed by concerted international collaboration. Globalization has become an increasingly important influence on dentistry and dental education. The International Federation for Dental Educators and Associations (IFDEA) welcomes the challenges it now faces as a player in a complex multifaceted global community. This report addresses the new circumstances in which IFDEA must operate, taking account of the recommendations made by other working groups. The report reviews the background and evolution of IFDEA and describes the extensive developments that have taken place in IFDEA over the past year with the introductions of a new Constitution and Bylaws overseen by a newly established Board of Directors. These were the consequence of a new mission, goals and objectives for IFDEA. An expanded organization is planned using as the primary instrument to facilitate the exchange of knowledge, programmes and expertise between colleagues and federated associations throughout the world, thereby promoting higher standards in oral health through education in low-, middle- and high-income countries of the world. Such aspirations are modified by the reality and enormity of poverty-related global ill health. [ABSTRACT FROM AUTHOR]

The aim of the present study was to identify and characterize polymorphisms within the 5′ flanking region, first exon and part of first intron of the bovine growth hormone gene among different beef cattle breeds: Nelore (n = 25), Simmental (n = 39), Simbrasil (n = 24), Simmental × Nelore (n = 30), Canchim × Nelore (n = 30) and Angus × Nelore (n = 30). Two DNA fragments (GH1, 464 bp and GH2, 453 bp) were amplified by polymerase chain reaction and then used for polymorphism identification by SSCP. Within the GH1 fragment, five polymorphisms were identified, corresponding to three different alleles: GH1.1, GH1.2 and GH1.3 (GenBank: , and , respectively). These allele sequences were aligned and compared with bovine GH gene nucleotide sequence (GenBank: and ), resulting in the identification of five insertion/deletions (INDELs) and five single nucleotide polymorphisms (SNPs). In the GH2 fragment two alleles were identified, GH2.1 and GH2.2 (GenBank: and , respectively). The allele sequences were compared with GenBank sequences ( , and ) and three INDELs and four SNPs were identified. In conclusion, we were able to identify six new polymorphisms of the bovine GH gene (one INDEL and five SNPs), which can be used as molecular markers in genetic studies. [ABSTRACT FROM AUTHOR]

- Controversy still exists as to whether oestrogens exert a direct effect on the prostatic cell. Incorporation of 75Selenomethionine (SeM) was used as a measure of protein synthesis by prostatic carcinoma cells in vitro to investigate the action of hormones on prostatic carcinoma cells in tissue culture. Stilboestrol (DES) and stilboestrol diphosphate (Honvan) inhibited protein synthesis in a proportion of patients, while testosterone was stimulatory. A similar effect was noted in cells from patients with benign hyperplasia (BPH). This work confirms that oestrogens have a direct inhibitory effect on prostatic cells at high concentrations which can be attained in patients given intravenous stilboestrol diphosphate. [ABSTRACT FROM AUTHOR]

- A study was performed on 130 men to compare the level of serum prostate-specific antigen (PSA) in controls, patients with benign prostatic hyperplasia (BPH) and patients with prostatic carcinoma. The results showed that all 30 normal controls below 40 years of age had values less than 10 ng/ml. Of the 40 patients with BPH, all aged over 40 years, 13 (32.5%) had raised levels above 10 ng/ml. In the 60 patients with prostatic carcinoma, all over 40 years, 24 had localised disease (M0) and 36 had metastatic spread (M1), as judged by isotope bone scan. In patients with M0 disease, 16 (66.6%) had raised PSA levels compared with 34 (94.5%) of those with M1 disease. The corresponding figures for raised prostatic acid phosphatase (PAP) values were 4% in the M0 group and 52.7% in the M1 group. PSA levels reflected neither the histological grade nor the local stage of the tumour and were of no value in estimating tumour burden. PSA was found to be a valuable index in the management of prostatic cancer because of this sensitivity. Stable disease not requiring hormonal manipulation was reflected by unchanging levels of PSA, whereas progressive disease requiring hormonal therapy was reflected by an alteration in the PSA levels corresponding to the patients' response. The same group of progressive disease patients showed only a 50% rise in serum PAP levels, confirming the greater sensitivity of PSA as a measure of prostate cancer. PSA measurements should be included in any further trials on prostatic carcinoma and should be regarded as a standard marker for evaluating response to therapy. [ABSTRACT FROM AUTHOR]

- Double J stents have been advocated for drainage or splintage of the ureter. One hundred and thirty-eight attempts at stent insertion were made in 100 patients. In 78% of attempts the stent was satisfactorily placed. Their use in retroperitoneal fibrosis, ureteric trauma and acute hydronephrosis of pregnancy has been encouraging. Poor results have been obtained in patients with malignant obstruction or tuberculous stricture. [ABSTRACT FROM AUTHOR]

In the field of tissue engineering, the study of cellular adhesion and migration is of crucial interest. Conducting polymers such as poly(3,4‐ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) provide an outstanding interface with biology due to their soft nature, which is closer to the mechanical, chemical, and morphological properties of biological systems. In this work, periodically micropatterned PEDOT:PSS thin films are used as a platform to investigate cellular migration. Human cerebral microvascular endothelial cells (hCMEC) show alignment and linear motion along PEDOT:PSS microstripes of varying widths (10–30 μm). In addition, an electrochemical gradient is created on the PEDOT:PSS film along these microstripes to influence the cell behavior. hCMEC cells linearly change their velocities depending on the redox state of the conducting polymer film. This work demonstrates the potential of such conducting polymer platforms to combine, at the same time, several key physicochemical factors for controlling cellular migration. In the future, we envision that these conducting polymer platforms will deliver tools for tissue regeneration and lead to new opportunities in regenerative medicine. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47029. Micropatterned PEDOT:PSS offers a promising platform for interfacing cells with electronics devices. In this study, we introduce the use of electrically driven PEDOT:PSS microstripes for controlling cell migration. First, our results show cells alignment on the PEDOT:PSS microstripes. Consequently, cells show a linear motion along the stripes, as well as a response to the electrochemical gradient created on the conducting film. [ABSTRACT FROM AUTHOR]

Chemical synapses are tiny and overcrowded environments, deeply embedded inside brain tissue and enriched with thousands of protein species. Many efforts have been devoted to developing custom approaches for evaluating and modifying synaptic activity. Most of these methods are based on the engineering of one or more synaptic protein scaffolds used to target active moieties to the synaptic compartment or to manipulate synaptic functioning. In this review, we summarize the most recent methodological advances and provide a description of the involved proteins as well as the operation principle. Furthermore, we highlight their advantages and limitations in relation to studies of synaptic transmission in vitro and in vivo. Concerning the labelling methods, the most important challenge is how to extend the available approaches to the in vivo setting. On the other hand, for those methods that allow manipulation of synaptic function, this limit has been overcome using optogenetic approaches that can be more easily applied to the living brain. Finally, future applications of these methods to neuroscience, as well as new potential routes for development, are discussed., (© 2022 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Introduction: Sexual function is often impaired in patients with chronic illnesses. Several patients with chronic gastrointestinal and liver disorders have been shown to suffer from sexual dysfunction, and celiac disease is a highly prevalent gastroenterological disorder., Aim: The aim of this study was to investigate the sexual function incidence and the risk factors for sexual dysfunction in both male and female celiac disease patients., Methods: Two hundred and eighty-four patients (170 females, 114 males) participated in this cross-sectional observational study in an anonymous manner. Female sexual function was assessed through the Female Sexual Function Index questionnaire. Male sexual function was assessed through the International Index of Erectile Function-5 questionnaire. Clinical-demographic variables were recorded. We investigated differences in the patient-reported outcomes among the different subgroups and whether there were clinical-demographic predictors of sexual dysfunction in our setting., Main Outcome Measures: Prevalence and assessment of sexual dysfunction in celiac disease patients., Results: In the female group, 85 subjects (50%) had a total score compatible with sexual dysfunction: 43 (61.42%) showed low desire, 79 (46.47%) showed arousal disorder, 66 (38.82%) lubrication disorder, and 84 (49.41%) inability of obtaining an orgasm. Also, a large proportion of our female patients, 161 (94.70%), showed sexual discomfort during intercourse. In the male group, 79 patients (62.2%) showed scores compatible with normal erectile function, eight (7.01%) had mild erectile dysfunction, 24 (21.05%) mild to moderate erectile dysfunction, and three (2.63%) presented severe erectile dysfunction. Altered body mass index was significantly associated with sexual dysfunction both in male and female patients. Early age at diagnosis was a significant predictor of sexual dysfunction in male celiac disease patients., Conclusions: A significant proportion of celiac disease patients present sexual dysfunction. Early age at diagnosis and high body mass index seem to predict sexual dysfunction in this clinical setting. Assessment of sexual function should be part of the initial evaluation of celiac disease patients in order to establish a prompt diagnosis and early treatment., (© 2022 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.)

Background: Heavy episodic drinking (HED) is a major public health problem among emerging adults (individuals 18 to 25), but with considerable heterogeneity in concurrent substance use and psychopathology. The current study used latent profile analysis (LPA) to detect discrete subgroups of HED based on alcohol, other drug severity, and concurrent psychopathology. A reinforcer pathology approach was used to understand motivational differences among the latent subgroups., Methods: Participants were 2 samples of emerging adults reporting regular HED, 1 Canadian (n = 730) and 1 American (n = 602). Indicators for the LPA were validated dimensional self-report assessments of alcohol severity, cannabis severity, other drug severity, nicotine dependence, depression, anxiety, posttraumatic stress disorder, and attention-deficit/hyperactivity disorder. Reinforcer pathology indicators were measures of alcohol demand, proportionate substance-related reinforcement, and discounting of future rewards., Results: The LPA yielded parallel 3-class solutions in both samples. The largest subgroup was characterized by comparatively low substance severity and psychopathology (Low overall severity). The second largest subgroup was characterized by comparatively high alcohol and other drug severity (excluding tobacco) and high levels of psychopathology (Heavy alcohol & high psychiatric severity). The third subgroup exhibited high alcohol, smoking and intermediate levels of other substance use and psychopathology (Heavy alcohol, smoking, & intermediate psychiatric severity). The Heavy alcohol & high psychiatric severity and Heavy alcohol, smoking, & intermediate psychiatric severity subgroups exhibited significantly higher alcohol demand, greater proportionate substance-related reinforcement, and steeper delay discounting., Conclusions: Parallel latent subgroups of emerging adults engaging in HED were present in both samples, and the high-risk subgroups were significantly differentiated by the reinforcer pathology indicators. These latent profiles may ultimately inform heterogeneity in the longitudinal course of HED in emerging adults., (© 2020 by the Research Society on Alcoholism.)

Immuno-chemotherapy elicit high response rates in B-cell non-Hodgkin lymphoma but heterogeneity in response duration is observed, with some patients achieving cure and others showing refractory disease or relapse. Using a transcriptome-powered targeted proteomics screen, we discovered a gene regulatory circuit involving the nuclear factor CYCLON which characterizes aggressive disease and resistance to the anti-CD20 monoclonal antibody, Rituximab, in high-risk B-cell lymphoma. CYCLON knockdown was found to inhibit the aggressivity of MYC-overexpressing tumours in mice and to modulate gene expression programs of biological relevance to lymphoma. Furthermore, CYCLON knockdown increased the sensitivity of human lymphoma B cells to Rituximab in vitro and in vivo. Strikingly, this effect could be mimicked by in vitro treatment of lymphoma B cells with a small molecule inhibitor for BET bromodomain proteins (JQ1). In summary, this work has identified CYCLON as a new MYC cooperating factor that autonomously drives aggressive tumour growth and Rituximab resistance in lymphoma. This resistance mechanism is amenable to next-generation epigenetic therapy by BET bromodomain inhibition, thereby providing a new combination therapy rationale for high-risk lymphoma., (© 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO.)

Background: Patients with multiple sclerosis (MS) are more frequently born in spring when compared to autumn. Fluctuation of UV-light has been hypothesized to drive this phenomenon., Aim: To assess the correlation between fluctuation of sunlight and birth season in persons with MS., Methods: For this record-linkage study, we collected from the international MSBase and the Italian MS iMed-web databases the dates of birth of 11,415 patients with MS from 36 centres from 15 countries worldwide and compared these to dates of live-births from national registries. From all participating sites, we collected data on UV-light fluctuation and assessed its correlation with seasonal fluctuation in MS births., Results: Compared with the reference cohort, an increased proportion of persons with MS were born in spring and a decreased proportion in autumn (odds ratio (OR) to be born in spring versus autumn = 1.158, χ² = 36.347, P < 0.001). There was no significantly increased fluctuation of MS births with increased quartile of ambient UV-light fluctuation (Ptrend = 0.086)., Conclusion: Seasonal fluctuation of MS births as found in this worldwide cohort of patients with MS did not correlate with variation in seasonal fluctuation of UV-light. Most likely, it results from a complex interplay between fluctuation of sunlight, behavioural factors, other environmental factors and (epi)genetic factors., (© 2012 John Wiley & Sons A/S.)

The present 0.25-hydrated form of rosiglitazone maleate [systematic name: (+/-)-2-({2-[2,4-dioxo-1,3-thiazolidin-5-ylmethyl)phenoxy]ethyl}methylamino)pyridinium maleate 0.25-hydrate], C(18)H(20)N(3)O(3)S(+) x C(4)H(3)O(4)(-) x 0.25 H(2)O, is a racemate with two independent moieties in the unit cell. Although the cation geometry does not differ substantially from that in the previously reported hydrochloride, the packing is quite different, the main feature being the formation of hydrogen-bonded tetramers, linked head-to-tail into weakly interacting chains.

Cytogenetic analysis is the gold standard for the follow-up of CML patients. The sensitivity of cytogenetics is fairly similar to that of Southern detection of M-BCR rearrangement (5%); this last technique has the potential advantage of being independent of cell division and yield of metaphases. IFN alpha treatment can induce lack of growth of hemopoietic precursors and poor yield of metaphases has been observed. For this reason we decided to study the grade of concordance and complementarity between analysis of karyotype and detection of M-BCR rearrangement of Southern blot. We studied 43 Ph1 positive, M-BCR positive pre-BMT CML patients (48 samples) treated with IFN alpha 2a. Karyotype was done on bone marrow cells by direct method, culture, and banding. Southern technique was performed onto DNA from peripheral blood leukocytes treated with BgIII (and Xbal if necessary) and hybridized with the universal probe (Ph1/bcr-3, Transprobe 1) labelled with dCTP32. A highly significant association between both tests was obtained. Of 48 samples analyzed, 34 were evaluable by both methods and 28 gave the same result for both tests. The concordance between the tests was good (kappa index: 0.63). Of total samples 27.1% was not evaluable by cytogenetics; this figure was 31.2% in samples from patients who were previously in complete cytogenetic response. All of the specimens not evaluable by karyotyping were evaluable by Southern. One sample was not analyzable by Southern but it was evaluable by cytogenetic analysis. The information obtained by Southern technique was clinically relevant, and decisions were made according to its results. We conclude that both tests show a significant association and a good concordance, although they are not interchangeable. Cytogenetic and molecular studies are complementary and must be employed together in CML patients treated with alpha-interferon.

We examined the effects of recombinant rat interferon-gamma (IFN-gamma) injections on the parasitologic, serologic, immunologic and histopathologic features of acute and chronic experimental Trypanosoma cruzi (T. cruzi) infections in "l" rats. Upon infection at weaning, two rat groups were allocated to receive a 20-day cycle of IFN-gamma injections, 20,000 IU/rat each, which started at 1, and 7 days post-infection (pi). Treatment with IFN-gamma, initiated at either 1 or 7 days pi, resulted in comparatively lower peak parasitemias (P < 0.02) but in similar levels of anti-T. cruzi circulating antibodies and serum IFN-gamma activities. The latter appeared significantly increased during acute infection whereas biologically active tumor necrosis factor was virtually undetectable in serum from infected rats regardless of whether they had been given IFN-gamma or not. The prevalence of chronic focal myocarditis in IFN-gamma-treated infected rats showed no differences with respect to the one recorded in control-infected counterparts. The inverse CD4/CD8 ratio of spleen and lymph node T cells that usually accompanies chronic infection was reversed by IFN-gamma. Mononuclear cells carrying class II I-A and I-E molecules, that were found to have increased at both compartments, appeared also modified upon IFN-gamma treatment with an overincrease of I-A-positive cells, and a normalization of I-E-bearing cells.

The NAD- and NADP-dependent aldehyde dehydrogenase (ALDH) activities were evaluated in two rat hepatoma cell lines, namely the well-differentiated MH1C1 line and the less differentiated HTC line. Each activity was determined in parallel in isolated rat hepatocytes, for comparison. The aliphatic aldehyde acetaldehyde (ACA) and the aromatic aldehyde benzaldehyde (BA) were used as substrates. With the first substrate the ALDH activities found in the crude cytoplasmic extracts were lower in hepatoma cells than in normal hepatocytes, especially when measured with NADP as coenzyme (ACA/NADP). Otherwise, with benzaldehyde as substrate the NAD-dependent enzyme activity (BA/NAD) was increased about 9-fold in HTC cells over hepatocytes and decreased in MH1C1 cells, while the NADP-dependent (BA/NADP) activity was increased 38- and 2.5-fold in HTC and MH1C1 cell lines, respectively. Studies on the subcellular distribution of these enzyme activities showed that the activity measured with acetaldehyde and NAD (ACA/NAD) was almost equally distributed between the cytosol and the subcellular particles in the three cell populations, but the ACA/NADP activity was shifted towards the cytosolic compartment in hepatomas, especially in HTC cells. The BA/NAD and BA/NADP ALDH activities found in the organelles of hepatoma cells were markedly reduced in comparison with hepatocytes, in favour of the cytosol. The most striking difference between the normal and the transformed cells was the 94-fold increase over hepatocytes of the BA/NADP activity, found in the cytosolic fractions of HTC cells. MH1C1 cells showed a less pronounced (7.5-fold) enhancement of this tumour-associated specific activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline elution was employed to study DNA damage in CHO-Kl cells treated with a series of biotic and xenobiotic aldehydes. DNA cross-linking was measured in terms of the reduction in the effect of methyl methanesulphonate on the kinetics of DNA elution and was observed in cells treated with formaldehyde, acetaldehyde, methylglyoxal and malonaldehyde. Propionaldehyde, valeraldehyde, hexanal and 4-hydroxynonenal produced DNA single-strand breaks, or lesions which were converted to breaks in alkali. Both types of DNA damage occurred in cells exposed to malealdehyde. These findings support the hypothesis of a carcinogenic effect of the aldehydic products (malonaldehyde, methylglyoxal, propionaldehyde, hexanal, 4-hydroxynonenal) released in biomembranes during lipid peroxidation.

A cell line derived from a Morris hepatoma, MH1C1, was examined for its in vitro expression of monooxygenases. These cells were found to contain different forms of cytochrome P450, as shown by the response to inducers, namely phenobarbital (PB), 3-methylcholanthrene (MC) and metyrapone (MP). MH1C1 cell monolayers exposed to PB or MC showed an increase in the concentration of two spectrally distinct forms of cytochrome P450. The PB and MC treatments elicited enzyme activities towards the substrates aminopyrine and benzo(a)pyrene, respectively. The cell treatment with metyrapone led to a simultaneous stimulation of aminopyrine demethylase and benzo(a)pyrene hydroxylase activities, so underlining the peculiar features of this inducer.

The metabolism of the toxic lipid peroxidation product 4-hydroxynonenal was investigated in the well-differentiated rat heptoma cell line MH1C1. When exposed to 0.1 mM 4-hydroxynonenal (HNE), MH1C1 cells consumed it in a time-dependent manner. There was a linear relationship between the amount of aldehyde consumed and cell number in the range 0.5 - 4 X 10(6) cells ml-1. This process was unaffected by pyrazole, suggesting that alcohol dehydrogenase is not involved. The whole homogenate of MH1C1 cells consumed added HNE at a rate similar to that in intact cells. Fractionation of the homogenate showed that the highest HNE-metabolizing activity is in the cytosol. The dialysed cytosol had almost no capacity to metabolize HNE, but this was restored by supplementation with NAD, NADH, NADP and NADPH. The metabolism of HNE in MH1C1 cells is thus different from that in hepatocytes, which were shown to utilize cytosolic alcohol dehydrogenase for this process. Both reductive and oxidative pathways could be implicated in the metabolic activity of MH1C1 cells towards HNE as well as binding by glutathione.