CAG repeat length in androgen receptor gene is not associated with amyotrophic lateral sclerosis.

BACKGROUND: Epidemiological and clinical studies show higher prevalence of amyotrophic lateral sclerosis (ALS) in males than in females and more severe lesions in androgen receptor (AR)-expressing tissues. The AR gene contains a polymorphic CAG trinucleotide repeat, whose expansion over a certain threshold is toxic to motor neurons, causing spinal and bulbar muscular atrophy (SBMA). PURPOSE AND METHODS: We tested the hypothesis that the AR CAG repeat linked to SBMA is a risk factor for ALS. We analyzed AR CAG expansions in 336 patients with ALS and 100 controls. RESULTS: We found a negative association of AR CAG expansions with ALS susceptibility, clinical presentation, and survival. CONCLUSIONS: Our findings do not support a role of the AR CAG repeat length in ALS.

[Colorectal oncogenesis]. / Oncogenèse colorectale.

Recent progress in the field of molecular biology has allowed us to identify at least two different molecular mechanisms implicated in colorectal carcinogenesis (CRC): chromosomal instability (CIN) and genetic instability. Even though the two molecular mechanisms differ, their signalling pathways, implicated in malignant transformation of colonic epithelial cells, appear to be similar. The most frequent group of CRC, which represents 80% of sporadic CRC, is characterized by allelic losses on the short arm of chromosome 17 and 8 and on the long arm of chromosome 5, 18 and 22. These allelic losses are associated with mutations in TP53, APC, SMAD2 and SMAD4 genes. All of these alterations are grouped under the phenotype CIN. A genetic instability termed MSI (microsatellite instability), which results from a mismatch repair (MMR) deficiency, appears in 12-15% of CRC cases. The presence of MMR deficiency leads to the accumulation of mutations in genes controlling cell cycle and apoptosis (TGFBRII, BAX or CASPASE5). More recently, the existence of a third phenotype was suggested. The main alteration associated with this group of tumors is the hypermethylation of the promoter region of numerous genes, leading to their inactivation. An activating mutation of BRAF is frequently associated with this phenotype. As described above, CRC shows genetic heterogeneity, however the consequences in terms of signalling pathway alterations are similar. For example, the activation of Wnt signalling pathways can result from the inactivation of the APC gene in the CIN phenotype or from an activating mutation in the ß-catenin gene in MSI tumors. The inactivation of TGFß pathways is also present in both tumor types and is driven by SMAD4, and more rarely by a SMAD2 inactivating mutation in CIN tumors, or by the existence of a frame-shift mutation occurring in a polyG coding track of the TGFß (transforming growth factor) receptor type II in MSI tumors. The RAS-MAP kinase pathway is activated by KRAS mutations in CIN tumors or by BRAF mutations in MSI tumors. The p53 pathway is inactivated by TP53 inactivation in CIN tumors or by BAX inactivating mutations in MSI tumors.

Effect of Fungicides and Storage Conditions on Postharvest Development of Citrus Black Spot and Survival of Guignardia citricarpa in Fruit Tissues.

Citrus black spot (CBS) is caused by Guignardia citricarpa, which incites lesions on citrus fruit and can induce fruit drop. Quiescent infections occur during the spring and summer, and symptoms appear at fruit maturity or after harvest. Thus, fruit from citrus areas affected by CBS represent a risk for introduction of this pathogen into new areas. The effects of preventive field fungicide programs, postharvest fungicide drenches, packinghouse fungicide applications, and storage temperatures on postharvest symptom development and viability of G. citricarpa in lesions were evaluated in five experiments on Murcott tangor, Valencia oranges, and lemons. Preventive field treatments and fruit storage at 8°C consistently reduced postharvest CBS development, whereas a postharvest fungicide drench or packinghouse treatment with fungicides had no effect on postharvest symptom development. In a separate experiment, postharvest appearance of symptoms was related to the percentage of fruit with symptoms at harvest. The preventive field fungicide program also consistently reduced the percentage of isolation of G. citricarpa from affected fruit, whereas storage temperature and packinghouse fungicide treatment gave variable results. The viability of the fungus declined with storage time of fruit after harvest, but G. citricarpa could still be readily isolated regardless of treatment. In another experiment, the viability of the fungus in detached fruit or peel was minimally affected by temperature or moisture during storage. The frequency of successful isolation declined with time, but G. citricarpa was still recovered frequently from symptomatic tissue at later times. The most effective means to reduce postharvest development of symptoms is through preventive application of fungicides during the fruit growing season and storage of harvested fruit at cold temperatures. None of the measures evaluated substantially reduced viability of G. citricarpa, and the pathogen would likely be introduced on symptomatic fruit from citrus areas with CBS.

Factors Affecting Pycnidium Production of Diaporthe citri on Detached Citrus Twigs.

Melanose, caused by Diaporthe citri, produces black-to-reddish brown lesions on twigs, leaves, and fruit of citrus and reduces the external quality of fruit destined for the fresh market. Inoculum for infection is produced primarily in pycnidia formed on dead twigs, and conidia are dispersed by rainwater. In laboratory studies, the effect of moisture, temperature, twig size, and melanose severity on pycnidium production on detached twigs was investigated. Pycnidium production was greatest when twigs were soaked for 3 to 4 h on alternate days three times per week and the temperature was 28°C. Production was greatest on twigs 3 to 5 mm in diameter and less on thinner or thicker twigs. Pycnidium production was related linearly to melanose severity on the twigs, and almost no pycnidia were produced on asymptomatic twigs. In the field, pycnidium production was greatest on detached, melanose-affected twigs placed in the canopy monthly during January to April than it was on twigs placed in the canopy during other months. The largest number of pycnidia was produced from May to August when fruit is most susceptible. The number of pycnidia produced was related significantly to degree-days above 20°C and weakly related to cumulative rainfall. Knowledge of inoculum production peaks may assist in timing of pruning and fungicide sprays.

Greenhouse Evaluation of Products That Induce Host Resistance for Control of Scab, Melanose, and Alternaria Brown Spot of Citrus.

Products that induce disease resistance in plants were evaluated on potted seedlings of rough lemon for citrus scab, caused by Elsinoe fawcettii; grapefruit for melanose, caused by Diaporthe citri; and Dancy tangerine for Alternaria brown spot caused by Alternaria alternata pv. citri. Plants were pruned to a single stem with mature leaves and treated at bud break or various times thereafter. New foliage was inoculated and subsequently evaluated for disease severity. Oxycom, Nutriphite, Messenger, Goemar H11, Serenade, ReZist, ProPhyt, Aliette, Actigard, and KeyPlex were evaluated and compared with benomyl or strobilurin fungicides as standards. Most products reduced disease severity compared with the untreated control, but were less effective than standard fungicides. The most generally effective products were ReZist and Actigard, those that contain or produce phosphorous acid (Aliette and Nutriphite), and a bacterial preparation (Serenade). Oxycom and Messenger controlled scab well in some tests. Products that induce host resistance may be useful for disease control in citrus in an integrated program with standard fungicides.

Influence of Environmental Factors on Severity of Citrus Scab and Melanose.

Citrus scab, caused by Elsinoe fawcettii, and melanose, caused by Diaporthe citri, produce external blemishes on citrus fruit, reducing acceptability of the fruit for the fresh market. In laboratory studies, rough lemon seedlings and grapefruit seedlings were inoculated with conidia of E. fawcettii and D. citri, respectively, and exposed to a range of temperatures and durations of leaf wetness. Scab was most severe at temperatures from 23.5 to 27°C and much less severe at 17, 20, 30, or 32°C. A leaf wetness duration of 4 h was sufficient for some infection, but 12 h of leaf wetness were needed for maximum infection with scab. Melanose was equally severe at 24 and 28°C, moderate at 20°C, and low at 32°C. Melanose infection was minimal with 4 h of leaf wetness, moderate with 8 to 16 h, and reached maximum levels at 24 h or more of leaf wetness. In field studies, grapefruit seedlings with new shoots were placed beneath trees weekly, and disease severity was evaluated in relation to environmental factors. Melanose severity increased sharply with an increase in total weekly rainfall, leaf wetness durations of greater than 80 h per week, and average temperatures above 22°C.

Outbreaks of Alternaria Brown Spot of Citrus in Brazil and Argentina.

Alternaria alternata (Fr.) Keissler causes lesions on leaves, twigs, and fruit and reduces yield and fruit quality of many tangerines (Citrus reticulata) and their hybrids (2). Severe outbreaks of Alternaria brown spot were observed on 'Murcott' tangor (Citrus reticulata × Citrus sinensis) trees in southern São Paulo, southern Minas Gerais states in Brazil, and in Misiones and Corrientes provinces in Argentina. A single diseased 'Fortune' tangerine tree was observed in a grove in Misiones. On young leaves, brown-to-black lesions often expanded to cover large parts of the leaf, causing abscission of young shoots and dieback of twigs. Lesions were often surrounded by yellow halos. On fruit, dark specks from 0.2 to 0.5 cm were observed, and severe infection caused premature fruit abscission. Isolations were made on potato dextrose agar (PDA) after surface sterilization of leaf and fruit tissues in 1.5% sodium hypochlorite for 1 min. Plates were incubated at 27°C in the dark for 1 week. Isolated colonies were olive brown to black, and the fungus was stimulated to form conidia by scraping the surface of the mycelium. The pathogen was a typical small-spored Alternaria species, and the morphological characteristics of the conidia and conidiophores fit the description of A. alternata. Inoculation of three detached young shoots of 'Murcott' with a conidial suspension (105 conidia per ml) confirmed pathogenicity of three isolates obtained from widely separated groves in southern and eastern São Paulo State in Brazil and one from Misiones Province in Argentina. A control treatment with an equal number of shoots was sprayed with distilled water only. After 48 h, all isolates caused dark lesions on the leaves, characteristic of the disease. Symptoms were observed on inoculated, but not on control shoots. Koch's postulates were satisfied by reisolation of the fungus from symptomatic tissue in all cases. Although Alternaria brown spot was reported previously in neighboring Rio de Janeiro, Brazil on 'Dancy' and 'Ponkan' tangerines (1), serious disease problems now occur on 'Murcott', an important commercial variety in the major production area in Brazil. To our knowledge, this is the first report of Alternaria brown spot in Argentina. References: (1) A. de Goes et al. Fitopatologia Brasileira 26(Suppl.):386, 2001. (2) L. W. Timmer et al. Pages 19-21 in: Compendium of Citrus Diseases. 2nd ed. L. W. Timmer, S. M. Garnsey, and J. H. Graham, eds. The American Phytopathological Society, St. Paul, MN, 2000.

Cognitive and other adverse effects of diphenhydramine use in hospitalized older patients.

BACKGROUND: Diphenhydramine hydrochloride is a commonly prescribed medicine in hospitalized patients, but its adverse effects on older patients remain unclear. METHODS: We enrolled 426 hospitalized medical patients aged 70 years or older in a prospective cohort study in a university hospital. Measurements included baseline and daily assessments including Mini-Mental State Examination scores, Confusion Assessment Method ratings, direct observations for medical devices (urinary catheter or physical restraints), and blinded medical record extractions for diphenhydramine use. RESULTS: Of the 426 patients, 114 (27%) received diphenhydramine during hospitalization and shared similar baseline characteristics including age, sex, delirium risk, and Mini-Mental State Examination scores compared with nonexposed patients. The diphenhydramine-exposed group was at an increased risk for any delirium symptoms (relative risk [RR], 1.7; 95% confidence interval [CI], 1.3-2.3) and for individual delirium symptoms, including inattention (RR, 3.0; 95% CI, 1.5-5.9), disorganized speech (RR, 5.5; 95% CI, 1.0-29.8), and altered consciousness (RR, 3.1; 95% CI, 1.6-6.1). Exposed patients also had increased risk for urinary catheter placement (RR, 2.5; 95% CI, 1.0-6.0) and longer median length of stay (7 vs 6 days; P =.009). A dose-response relationship was demonstrated for most adverse outcomes. Overall, 24% of diphenhydramine doses were administered inappropriately. CONCLUSIONS: Diphenhydramine administration in older hospitalized patients is associated with an increased risk of cognitive decline and other adverse effects with a dose-response relationship. Careful review of its use is necessary in this vulnerable population.

Accuracy of CT in estimating extent of pancreatic necrosis.

The objective of this study was to determine whether nonenhancing pancreatic lesions are accurate in estimating pancreatic necrosis. Twenty-six consecutive abdominal computed tomography (CT) examinations performed over a 3-year period that met the CT criteria for pancreatic necrosis were reviewed. Follow-up CTs in three of 26 patients demonstrated pancreatic enhancement, indicating viable parenchyma, within the previously nonenhancing regions. All three patients had undergone surgical debridement in that area. Twenty-three cases demonstrated either no change or enlargement of the nonenhancing pancreatic lesions. Follow-up ranged from 1 week to 26 months. While CT is accurate in diagnosing pancreatic necrosis, lack of enhancement in CT may occasionally overestimate the extent of necrosis. Nonenhancing, viable but at-risk tissue may be present adjacent to frankly necrotic tissue. Surgical debridement may facilitate recovery of this viable tissue, which may enhance normally on follow-up CT.

Routine pre-contrast CT for liver lesion detection. A re-examination.

OBJECTIVE: Re-examination of routine pre-contrast computed tomography (CT) through liver. MATERIALS AND METHODS: 852 abdominal CTs including pre- and post-contrast images were retrospectively reviewed regarding detection of hepatic lesions. RESULTS: 103 cases demonstrated hepatic abnormalities. More liver lesions were identified post-contrast in 89; equal numbers were seen pre- and post-contrast in 10; more lesions were seen pre-contrast in one case. Tiny calcifications were detected only pre-contrast in three cases. CONCLUSIONS: Routine pre-contrast scanning through liver is not cost-effective.

Chromosome damage in underground coal miners: detection by conventional cytogenetic techniques and by submitting lymphocytes of unexposed individuals to plasma from at-risk groups

Estudos citogenéticos foram realizados em mineiros de carväo mineral de Criciúma (SC) e em controle fumantes e näo-fumantes selecionados por sexo e idade. Nas culturas de linfócitos da amostra de mineiros observamos uma diminuiçäo do índice mitótico e um excesso de fragmentos cromossômicos e em células da mucosa oral um excesso de micronucleos. Um ensaio alternativo para detecçäo de clastogênese em casos de exposiçäo ocupacional foi testado: os linfócitos de indivíduos näo expostos foram submetidos a uma mistura de plasmas de mineiros e também a uma mistura de plasmas de indivíduos näo-expostos, com a finalidade de servirem como controles pareados no experimento realizado. Os resultados revelaram que o teste é muito conveniente, uma vez que linfócitos dos mesmos indivíduos podem ser utilizados tanto como alvo como controle. Neste experimento detectamos um aumento de falhas cromatídicas, fragmentos e alteraçöes cromossômicas em geral nos linfócitos expostos a mistura de plasmas de mineiros. A mistura de plasmas dos controle näo induziu nenhuma alteraçäo significante, indicando que os resultados obtidos näo foram devidos ao efeito de adiçäo das misturas de plasmas per se.

[Recurrent anterior and multidirectional instability of the shoulder]. / Instabilité antérieure récidivante avec hyperlaxité multidirectionnelle de l'épaule.

PURPOSE OF THE STUDY: Surgical treatment for recurrent anterior instability associated to multidirectional shoulder hyperlaxity: results analysis. MATERIAL: Twenty five patients operated for recurrent anterior dislocation or subluxation with multidirectional hyperlaxity. Age at operation was low (22 years old), there were more females than males, instability was bilateral in 52 per cent cases. METHOD: Five patients underwent a capsular shift followed by a four weeks post operative immobilization. Twenty patients underwent a bone block procedure with the coracoid process associated with a modified capsular shift. Inferior half of the subscapularis muscle was left intact under the coraco-biceps tendon. RESULTS: The results were fair with only 52 per cent excellent or good results. Ten patients (40 per cent) presented a recurrence either a dislocation or a subluxation. Hyperlaxity recurred in all but three patients. The procedure didn't influence the results which were related to the antecedent: the patients with a previous history of voluntary recurrent posterior subluxations achieved 33 per cent fair or poor results. Patients with previous history of recurrent anterior subluxation achieved 100 per cent poor results, whereas the patients without antecedent achieved 85 per cent good to excellent results. DISCUSSION: Establishing a difference between laxity and instability helps to analyse the patients with an unstable shoulder rather than considering traumatic or atraumatic onset of the instability. Identification of the hyperlaxity and of the antecedents must influence the therapeutic discussion. CONCLUSION: We recommend to use the term multidirectional hyperlaxity rather than multidirectional instability to characterize these patients.

Molecular evidence for nitric oxide-mediated motor neuron development.

The complex morphological, electrophysiological and molecular properties of the adult vertebrate nervous system emerge over an extended period in prenatal and early postnatal life. Numerous studies have shown that synaptic activity plays a key role in the postnatal acquisition of mature neuronal phenotype. The cellular and molecular mechanisms subserving activity-dependent development are largely unknown. Several lines of evidence suggest that a rise in intracellular Ca2+ as a consequence of synaptic activity may regulate neuronal differentiation through its interactions with calcium-activated signal transduction molecules such as calcium/calmodulin kinase type II, protein kinase C or nitric oxide synthase (NOS). The aim of the present study is to identify potential signal transduction events subserving postnatal motor neuron development. Here we show that NOS antagonists block the molecular maturation of motor neurons and this effect is likely to be mediated by a subpopulation of ventral horn cells that express NOS transiently during early postnatal life. These results suggest that the local production of nitric oxide within the ventral horn may contribute to a late phase in motor neuron differentiation.

Frequencies of chromosomal aberrations in rodents collected in the coal-field and tobacco culture region of Criciúma, south Brazil.

The present work has been accomplished in the basin of the Sangão River (Criciúma, South Brazil), which receives the rejects from coal washing, mainly heavy metals. In the tobacco cultures at the river banks several agrotoxics are used. We tried to detect and estimate the possible action of this environmental pollution on rodents directly exposed to it through the study of chromosome aberration frequency in the bone marrow. The same methodology was applied to rodents collected from a nonpolluted area of the same state (Florianópolis, 190 km from Criciúma). The results obtained showed significant differences in total chromosome aberrations at the different sites. There is therefore a suggestion that this methodology could be applied to detect the action of environmental pollution on organisms.