Variantes en la presentación clínica de la enfermedad por arañazo de gato en niños del hospital Garrahan / Variants in the clinical presentation of cat scratch disease in children at Garrahan Hospital

La infección por Bartonella henselae (BH) adopta diversas formas de presentación clínica en pediatría. Según la bibliografía la forma de presentación más frecuente en pacientes inmunocompetentes es la linfadenopatía única asociada a fiebre. En el 85 % de los casos se compromete un solo ganglio siendo los axilares y los epitrocleares los más frecuentemente involucrados. Existen otras formas de presentación menos frecuentes que debemos tener en consideración, para poder realizar un diagnóstico precoz e indicar un tratamiento adecuado si así lo requiere. El diagnóstico requiere de la sospecha clínica del equipo de salud tratante, junto al antecedente epidemiológico, los hallazgos clínicos del examen físico y la realización de serologías que incluyan el dosaje de inmunoglobulina M y G. Los objetivos del presente trabajo fueron reconocer las manifestaciones clínicas típicas y atípicas de la EAG por Bartonella henselae, describir la epidemiología, características clínicas y evolución de esta enfermedad que se presentaron en nuestro hospital. Se estudiaron un total de 187 pacientes. La media de edad fue de 7.6 años (rango 1-14); siendo 53.5% de género masculino. Las formas de presentación más frecuentes en nuestro trabajo fueron la adenitis y la fiebre. La mayoría recibió diversos esquemas de tratamiento antibiótico, secundario al retraso en el diagnóstico. La tasa de hospitalización fue muy baja, remitió con tratamiento ambulatorio con antibióticos o sin ellos (AU)

Bartonella henselae infection has different clinical presentations in pediatrics. According to the literature, the most common form of presentation in immunocompetent patients is single lymphadenopathy associated with fever. In 85 % of the cases a single lymph node is involved, with the axillary and epitrochlear nodes being the most commonly involved. There are other, less frequent, forms of presentation that should be taken into consideration in order to make an early diagnosis and indicate appropriate treatment if required. Diagnosis relies on clinical suspicion by the treating healthcare team, together with the epidemiological history, clinical findings on physical examination, and serology including immunoglobulin M and G dosage. The objectives of this study were to identify both the typical and atypical clinical manifestations of Bartonella henselae cat scratch disease, to describe the epidemiology, clinical characteristics, and outcomes of cases presenting at our hospital. A total of 187 patients were studied. The mean age was 7.6 years (range 1-14); 53.5% were male. The most frequent forms of presentation in our study were adenitis and fever. Most of them received different antibiotic treatment regimens due to delayed diagnosis. The hospitalization rate was very low and the disease typically resolved with outpatient treatment, with or without antibiotics (AU)

Impact of chemotherapy on surgical outcomes in ileostomy reversal: a propensity score matching study from a single centre.

PURPOSE: In patients with chemotherapy, there is no consensus on the timing of ileostomy closure. Ileostomy reversal could improve the quality of life and minimise the long-term adverse events of delayed closure. In this study, we evaluated the impact of chemotherapy on ileostomy closure and searched for the predictive factors for complications. METHODS: We retrospectively analysed 212 patients with rectal cancer who underwent ileostomy closure surgery during and without chemotherapy and were consecutively enrolled between 2010 and 2016. As a result of the heterogeneity of the two groups, propensity score matching (PSM) was performed with a 1:1 PSM cohort. RESULTS: A total of 162 patients were included in the analysis. The overall stoma closure-related complications (12.4% vs. 11.1%, p = 1.00) and major complications (2.5% vs. 6.2%, p = 0.44) were not significantly different between the two groups. Multivariate analysis demonstrated that chronic kidney disease and bevacizumab use are risk factors for major complications. CONCLUSION: Patients with oral or intravenous chemotherapy can safely have ileostomy closure with an adequate time delay from chemotherapy. When patients use bevacizumab, major complications related to ileostomy closure should still be cautioned.

Optimization of the spherical integrity for sustained-release alginate microcarriers-encapsulated doxorubicin by the Taguchi method.

This study aimed to develop biodegradable calcium alginate microcarriers with uniform particle size and spherical integrity for sustained-release targeting transarterial chemoembolization. To determine related parameters including the ratio of cross-linking volume (sodium alginate: CaCl2), concentrations of sodium alginate and CaCl2 solutions, collection distance, flow rate, stirring speed, syringe needle diameter and hardening time to fabricate the microcarriers, the Taguchi method was applied. Using different conditions, a total of 18 groups were prepared. The average size of microspheres from different groups was estimated as ~ 2 mm (range 1.1 to 1.6 mm). Signal-to-noise ratio analysis showed the optimal spherical integrity (F1) achieved when the above parameters were designed as 0.1, 2.5 wt%, 6 wt%, 8 cm, 30 mL/h, 150 rpm, 0.25 mm and 2 h, respectively. The best (F1), middle (F2) and worst (F3) groups were used for further experiments. Fourier-transform infrared spectroscopy spectrum showed that F1, F2 and F3 conformations were distinct from original sodium alginate. Drug-loaded calcium alginate microcarriers demonstrated rougher surfaces compared to microspheres without drug under transmission electron microscopy. Compared to pH 7.4, swelling rates in PBS were decreased at pH 6.5. Encapsulation and loaded efficiencies of the Dox-loaded microcarriers were estimated as ~ 40.617% and ~ 3.517%. In vitro experiments indicated that the F1 Dox-loaded microcarriers provide a well sustained-release efficacy for about two weeks at 37 °C in PBS. Treatments of calcium alginate microcarriers without the Dox in two distinct hepatocellular carcinoma-derived cell lines, Huh-7 and Hep-3B, indicated that these microcarriers were non-toxic. The Dox-loaded microcarriers displayed sustained-release capacity and reduced cell viabilities to ~ 30% in both cell lines on Day 12.

Outcomes of Heart Transplant Recipients With Preexisting Malignancies.

BACKGROUND: Ensuring careful selection of heart transplant recipients with pretransplant malignancies (PTM) has been suggested in several retrospective studies. However, cancer survival rates continue to increase and we still lack outcomes data on PTM patients who have undergone heart transplantation (HT) within the Asian region. Herein we report pretransplant characteristics and outcomes among PTM patients with HT. METHODS: A total of 354 patients underwent HT from January 2004 to January 2016. Eight of these patients had a history malignancy that was being treated before transplantation. Posttransplant outcomes and clinical characteristics were collected and possible prognostic factors analyzed. RESULTS: The median age of the patients with a preexisting malignancy was 60 years. The PTM group included 5 males and 3 females, with a median duration of follow-up of 43 months. In this group there were 2 patients with lymphoma after chemotherapy, 1 with colon cancer postoperatively, and 1 was on chemotherapy. In the other 4 patients, nasopharyngeal cancer, thyroid cancer, breast cancer, and endometrial cancer were identified, and each had undergone treatment. Only 1 premalignancy patient, with nasopharyngeal cancer, had disease recurrence. The 5-year overall survival of these patients was 50.0 ± 17.7%, but 5-year survival for those without PTM was 68.7 ± 2.0%. CONCLUSION: PTM was 2.3% in our cohort. PTM is associated with an increased risk of all-cause mortality. Thus, our findings suggest careful consideration when selecting PTM patients for HT.

Renal Function Changes Under Everolimus Plus Cyclosporine or Everolimus Plus Tacrolimus After Heart Transplantation.

Everolimus (EVR) can be used with calcineurin inhibitors to reduce the risk of renal dysfunction, with similar immunosuppressive effect. In this study, we compared renal function after heart transplantation (HT) under EVR with cyclosporine (CSA) or tacrolimus (TAC). Between 2004 and 2014, EVR with CSA or TAC was used in 117 HT at the National Taiwan University Hospital. After HT, all patients received corticosteroid, EVR (C0 target 3-8 ng/mL) and CSA (C0 blood level 100-200 ng/mL), or TAC (Co blood level 5-10 ng/mL). Renal function was evaluated before HT, every month after HT for up to 1 year, and then every 3 months for up to 2 years. Blood-drug levels of EVR, CSA, and TAC were also monitored simultaneously with renal function. The estimated mean glomerular filtration rate (eGFR) was 76.5 mL/min/1.73 m2 before HT. After HT, the eGFR was 64 mL/min/1.73 m2 at the third month, and 64 mL/min/1.73 m2 at the end of first year. The difference was significant between pre-HT and post-HT (P = .00) during the first year. No significant differences were noted between the CSA and TAC groups. Careful monitoring of blood-drug level and renal function is crucial after heart transplantation. It is concluded that under close monitoring blood-drug level and renal function, it is possible to reach acceptable postoperative renal function with no difference of renal function between EVR plus CSA and EVR plus TAC.

Evidence for linkage of migraine in Rolandic epilepsy to known 1q23 FHM2 and novel 17q22 genetic loci.

Migraine headaches are a common comorbidity in Rolandic epilepsy (RE) and familial aggregation of migraine in RE families suggests a genetic basis not mediated by seizures. We performed a genome-wide linkage analysis of the migraine phenotype in 38 families with RE to localize potential genetic contribution, with a follow-up in an additional 21 families at linked loci. We used two-point and multipoint LOD (logarithm of the odds) score methods for linkage, maximized over genetic models. We found evidence of linkage to migraine at chromosome 17q12-22 [multipoint HLOD (heterogeneity LOD) 4.40, recessive, 99% penetrance], replicated in the second dataset (HLOD 2.61), and suggestive evidence at 1q23.1-23.2, centering over the FHM2 locus (two-point LOD 3.00 and MP HLOD 2.52). Sanger sequencing in 14 migraine-affected individuals found no coding mutations in the FHM2 gene ATP1A2. There was no evidence of pleiotropy for migraine and either reading or speech disorder, or the electroencephalographic endophenotype of RE when the affected definition was redefined as those with migraine or the comorbid phenotype, and pedigrees were reanalyzed for linkage. In summary, we report a novel migraine susceptibility locus at 17q12-22, and a second locus that may contribute to migraine in the general population at 1q23.1-23.2. Comorbid migraine in RE appears genetically influenced, but we did not obtain evidence that the identified susceptibility loci are consistent with pleiotropic effects on other comorbidities in RE. Loci identified here should be fine-mapped in individuals from RE families with migraine, and prioritized for analysis in other types of epilepsy-associated migraine.

A comparative study of flow cytometric T cell receptor Vß repertoire and T cell receptor gene rearrangement in the diagnosis of large granular lymphocytic lymphoproliferation.

INTRODUCTION: Large granular lymphocytes (LGLs) are medium- to large-sized lymphocytes with azurophilic cytoplasmic granules. Reactive vs. neoplastic LGLs are usually morphologically indistinguishable. METHODS: We investigated 25 consecutive cases of LGL lymphoproliferation using flow cytometric T cell receptor Vß (FC-Vß) repertoire and T cell receptor gene rearrangement (TCR-GR) in detecting clonality. RESULTS: Seventeen patients (68%) were T-LGL leukemia (T-LGLL) with a male predominance, a median age of 67, and a median absolute LGL count of 2.592 × 10(9) /L. All cases were clonal using the FC-Vß analysis, and all but one (94%) was clonal by TCR-GR. Eight patients (32%) had reactive LGL lymphoproliferation. Two had EBV-associated infectious mononucleosis; one was clonal by both FC-Vß and TCR-GR; and the other was clonal only by TCR-GR. The remaining six cases were polyclonal by both assays. Patients with reactive LGL lymphoproliferation were more frequently associated with an underlying/concurrent malignancy than those with T-LGLL (4/8 cases vs. 1/17; P = 0.023, Fisher's exact test). We compared the demographic, hemogram, and clonality data between these two groups and found that the only significant difference was the lower median platelet count in the LGL lymphocytosis group (201 × 10(9) /L vs. 223 × 10(9) /L; P = 0.031; Student's t-test). A literature review including the current study showed a high sensitivity of FC-Vß analysis for T-LGLL (97.2%; 107/110 cases). CONCLUSIONS: FC-Vß analysis was slightly more sensitive than TCR-GR for the detection of clonal T cell lymphoproliferation. However, we must interpret the laboratory findings with clinical context as clonal T cell lymphoproliferation may occur in patients with viral infection.

Acute mental disturbance caused by synthetic cannabinoid: a potential emerging substance of abuse in Hong Kong.

Synthetic cannabinoids are hybrid herbal/chemical products which mimic the effects of cannabis. They are usually marketed as incense or 'herbal smoking blend', and best known by the brand names 'K2' and 'Spice'. Their popularity among recreational drug abusers has grown rapidly due to their easy availability, relatively low cost, non-detection by conventional drug tests, and ease of concealing their use from family and authorities. They took Europe and later North America by storm in the late 2000s, yet limited medical literature exists detailing their adverse effects. They began to emerge in the Hong Kong drug scene in 2009. We report on a man who developed acute mental disturbance after 4 weeks of daily K2 abuse. This is the first case report of mental disorder caused by synthetic cannabinoid abuse in a Chinese.

Prenatal and postnatal risk factors for infantile pneumonia in a representative birth cohort.

Pneumonia is an important cause of mortality and morbidity in infants. However, information of risk factors for pneumonia in children aged <6 months is limited. This study aimed to evaluate the risk factors and their contribution to infantile pneumonia in a large population-based survey. Of 24,200 randomly sampled main caregivers invited, 21,248 (87.8%) participated in this study. A structured questionnaire was used to interview the main caregivers. Information regarding whether hospitalization was required, family environment, and medical history were obtained. The prevalence of pneumonia was 0.62% in our study cohort. Multivariate logistic regression analysis showed that preterm birth, congenital cardiopulmonary disease, antibiotic use during pregnancy, maternal overweight, daily prenatal exposure to environmental tobacco smoke, maternal smoking during pregnancy, and visible mould on walls at home are risk factors associated with infantile pneumonia. Further study is warranted to investigate the causality and mechanisms of these novel factors.

Endoscope-assisted transoral excision of a huge parapharyngeal pleomorphic adenoma.

The treatment of choice for a parapharyngeal pleomorphic adenoma is total surgical resection. We describe an endoscope-assisted transoral excision of a huge parapharyngeal pleomorphic adenoma, and discuss the benefits of this type of operation.

Increased serum osteopontin is a risk factor for osteoporosis in menopausal women.

SUMMARY: Osteopontin (OPN)-deficient mice are resistant to ovariectomy-induced osteoporosis. Therefore, we hypothesized that women with OPN overexpression may show less resistance to postmenopausal osteoporosis. In this study, we first demonstrated that serum OPN levels could be used as a biomarker for the early diagnosis of osteoporosis in postmenopausal women. INTRODUCTION: Animal studies indicate that OPN-deficient mice are resistant to ovariectomy-induced osteoporosis. METHODS: From 2004 to 2006, 124 women over the age of 45 were enrolled in a menopausal group, while another 95 women, from 25 to 45 years of age with regular menstruation, were enrolled into a childbearing age group. The serum concentrations of OPN were calculated using the enzyme-link immunosorbent assay method, and bone mineral densities were determined with dual energy X-ray absorptiometry. RESULTS: Serum OPN levels had a significant positive correlation with age (menopausal group, p < 0.0001) and a negative correlation with body weight, height, hip bone mineral density, and T-scores in the menopausal group. In contrast, there was a positive correlation with the E2 concentration and height, but there was no significant association with the above variables in the childbearing age group. Additionally, high serum OPN levels (>14.7 ng/ml) was a significant risk factor causing menopausal osteoporosis (odds ratio = 2.96, 95% confidence interval, 1.055-8.345). CONCLUSION: Serum OPN levels could be used as a biomarker for the early diagnosis of osteoporosis in postmenopausal women.

Low-energy helium-neon laser induces melanocyte proliferation via interaction with type IV collagen: visible light as a therapeutic option for vitiligo.

BACKGROUND: The treatment of vitiligo remains a challenge for clinical dermatologists. We have previously shown that the helium-neon laser (He-Ne laser, 632.8 nm) is a therapeutic option for treatment of this depigmentary disorder. OBJECTIVES: Addressing the intricate interactions between melanocytes, the most important cellular component in the repigmentation scheme of vitiligo, and their innate extracellular matrix collagen type IV, the current study aimed to elucidate the effects of the He-Ne laser on melanocytes. METHODS: Cultured melanocytes were irradiated with the He-Ne laser. Relevant biological parameters including cell attachment, locomotion and growth were evaluated. In addition, the potentially involved molecular pathways were also determined. RESULTS: Our results show that in addition to suppressing mobility but increasing attachment to type IV collagen, the He-Ne laser stimulates melanocyte proliferation through enhanced alpha2beta1 integrin expression. The expression of phosphorylated cyclic-AMP response element binding protein (CREB), an important regulator of melanocyte growth, was also upregulated by He-Ne laser treatment. Using a specific mitochondrial uncoupling agent [carbonyl cyanide m-chlorophenyl-hydrazone (CCCP)], the proliferative effect of the He-Ne laser on melanocytes was abolished and suppression of melanocyte growth was noted. CONCLUSIONS: In summary, we have demonstrated that the He-Ne laser imparts a growth stimulatory effect on functional melanocytes via mitochondria-related pathways and proposed that other minor pathways including DNA damage may also be inflicted by laser treatment on irradiated cells. More importantly, we have completed the repigmentation scheme of vitiligo brought about by He-Ne laser light in vitro and provided a solid theoretical basis regarding how the He-Ne laser induces recovery of vitiligo in vivo.

Recent development of peptides from glycoproteins IIb (alphaIIb) and IIIa (beta3) that inhibit platelet fibrinogen binding.

The glycoprotein (GP) IIb/IIIa (alphaIIbbeta3) found on platelets binds fibrinogen when platelets are activated, thereby mediating the platelet aggregation process. Blockading of alphaIIbbeta3 has been proposed to prevent platelet aggregation independent of the substance(s) responsible for activating the platelets. This inhibition of platelet aggregation is thought to be an effective therapeutic approach to various thromboembolic syndromes. The development of various forms of alphalambdapietaalpha;IIbbeta3 inhibitors has resulted in the inhibition of platelet aggregation, although studies of alphaIIbbeta3 receptor function and various alphaIIbbeta3 inhibitors have demonstrated the potential for these agents to produce effects on other aspects of platelet function as well as having non-platelet effects. This review describes the newly derived peptides from 1) glycoprotein IIb (alphaIIb) that interferes with platelet aggregation by inhibiting the binding of fibrinogen to alphaIIbbeta3 and from 2) GP IIIa (beta3) by blocking the alphaIIbbeta3 complex formation. These peptides may become effective agents to block the interaction of ADP, type I collagen, and type III collagen (type I collagen and type III collagen are present in abundant amounts in blood vessel walls) with platelets.

Cancer aggregation and complex segregation analysis of families with female non-smoking lung cancer probands in Taiwan.

Previous studies have found that having a first-degree blood relative with lung cancer was a possible predictor of lung cancer risk, but some studies have indicated that the association is non-significant or only significant for a subset of the studied population. To determine the familial aggregation and whether there is any evidence for a gene controlling the susceptibility to developing lung cancer in female non-smokers, multiple logistic regression methods for estimating covariate effects and maximum likelihood segregation analyses were performed using data from 216 female non-smoking lung cancer probands (2328 individuals) in a population-based case-control study. Having a family history of lung cancer was found to be a significant predictor of lung cancer for non-smoking females (Adjusted Odds Ratio (OR)=5.7, 95% Confidence Interval (CI)=1.9-16.9). Having a female relative with lung cancer (adjusted OR=14.4, 95% CI=2.7-75.5) was more strongly associated with the lung cancer risk than was having a male relative with lung cancer. This association was stronger for probands aged less than 60 years at onset (adjusted OR=11.2, 95% CI=2.2-56.9). All of the Mendelian models fitted the data significantly better than the sporadic (no major type) model or the environmental model (P<0.00l). The Mendelian codominant models provided the best fit of the data for the early onset probands and showed a stronger effect for a major susceptibility locus for non-smoking lung cancer probands. The results of this study provide evidence that a rare autosomal codominant gene may influence the risk lung cancer in non-smoker and is responsible for the familial aggregation observed in non-smoking lung cancer patients.

Promoter CpG methylation of Hox-a10 and Hox-a11 in mouse uterus not altered upon neonatal diethylstilbestrol exposure.

Mouse abdominal B-like Hoxa genes are expressed and functionally required in the developing reproductive tracts. Mice lacking either Hoxa-10 or Hoxa-11, two of the AbdB Hoxa genes, exhibit abnormal uterine development similar to that induced by in utero diethylstilbestrol (DES) exposure. Indeed, uterine Hoxa-10 and Hoxa-11 expression is potently repressed by perinatal DES exposure, providing a potential molecular mechanism for DES-induced reproductive tract malformations. We have shown previously that DES can permanently alter uterine lactoferrin gene expression through modulation of the lactoferrin promoter methylation pattern. Here we ask whether a similar mechanism also functions to deregulate uterine Hoxa-10 or Hoxa-11 expression during neonatal DES exposure. We mapped the Hoxa-10 promoter by cloning a 1.485 kb DNA fragment 5' of the Hoxa-10 exon1a. A 5' rapid amplification of cDNA ends (RACE) experiment revealed a transcription start site for the a10-1 transcript. Functional analysis of the proximal 200-bp sequences demonstrated significant promoter activity, confirming the location of the Hoxa-10 promoter. Moreover, methylation assays performed on eight CpGs in Hoxa-10 and 19 CpGs in Hoxa-11 proximal promoters demonstrated that all these CpGs were highly unmethylated in both control and DES-dosed mice from postnatal day 5 to day 30. Significant methylation around Hoxa-10 and Hoxa-11 promoters was only observed in DES-induced uterine carcinomas in 18-mo-old mice. Our results suggest that DES-induced downregulations of Hoxa-10 or Hoxa-11 gene expression are not associated with methylation changes in their proximal promoters and that gene imprinting by developmental DES exposure may be a gene-specific phenomenon.

Chloroplast DNA phylogeography of Cunninghamia konishii (Cupressaceae), an endemic conifer of Taiwan.

In this study, we investigated the genetic structure and phylogeographic pattern of the genus Cunninghamia, a member of the Cupressaceae restricted to mainland China and Taiwan, based on sequences of the trnD-trnT noncoding spacer of the chloroplast DNA. Maternal inheritance of chloroplasts was determined experimentally. No paternal leakage was detected. Both parsimony and neighbor-joining analyses revealed the polyphyly of Cunninghamia konishii, populations of which were nested in clades of C. lanceolata from mainland China. The nucleotide diversity of chloroplast DNA sequences within C. konishii (0.0118) was higher than that between species (0.0104), which agrees with a previous allozyme investigation. Based on mutational differences between sequences, a minimum spanning network consisting of five clades was constructed. Significant genetic differentiation (phiST = 0.130, P < 0.001) was detected between the clades based on AMOVA analyses. We infer several possible refugia in the Yunnan, Zhejiang, and Guangdong provinces of south China, all located in the minimum network as interior nodes. We also infer possible migration routes of Cunninghamia populations. The phylogeographic pattern shown in the reconstructed network suggests that the present-day Cunninghamia populations in Taiwan were derived from six different sources in continental Asia via long-distance seed dispersal. A migrant-pool model explains the heterogeneous composition of the organelle DNA in Taiwan's populations and the low differentiation between populations of Taiwan and China (phiCT = 0.012, P = 0.454). In contrast with the genetic heterogeneity within geographic populations, many local populations have attained coalescence at the trnD-trnT alleles, which has led to significant differentiation at the population level.

Identification and characterization of a novel androgen receptor coregulator ARA267-alpha in prostate cancer cells.

The androgen receptor (AR) is a member of the steroid receptor superfamily that binds to the androgen response element to regulate target gene transcription. AR may need to interact with some selected coregulators for maximal or proper androgen function. Here we report the isolation of a new AR coregulator with a calculated molecular mass of 267 kDa named the androgen receptor-associated protein 267-alpha (ARA267-alpha). ARA267-alpha contains 2427 amino acids, including one Su(var)3-9, Enhancer-of-zeste, and Trithorax (SET) domain, two LXXLL motifs, three nuclear translocation signal (NLS) sequences, and four plant homeodomain (PHD) finger domains. Northern blot analyses reveal that ARA267-alpha is expressed predominantly in the lymph node as 13- and 10-kilobase transcripts. HepG2 is the only cell line tested that does not express ARA267-alpha. Yeast two-hybrid and glutathione S-transferase pull-down assays show that both the N and C terminus of ARA267-alpha interact with the AR DNA- and ligand-binding domains. Unlike other coregulators, such as CBP, which enhance the interaction between the N and C terminus of AR, we found that ARA267-alpha had little influence on the interaction between the N and C terminus of AR. Luciferase and chloramphenicol acetyltransferase assays show that ARA267-alpha can enhance AR transactivation in a dihydrotestosterone-dependent manner in PC-3 and H1299 cells. ARA267-alpha can also enhance AR transactivation with other coregulators, such as ARA24 or PCAF, a histone acetylase, in an additive manner. Together, our data demonstrate that ARA267-alpha is a new AR coregulator containing the SET domain with an exceptionally large molecular mass that can enhance AR transactivation in prostate cancer cells.

Gene imprinting in developmental toxicology: a possible interface between physiology and pathology.

Gene imprinting is an epigenetic mechanism for accomplishing persistent change in gene expression. In this brief paper, we explore the mechanisms for imprinting genes and present data showing that the synthetic estrogen, diethylstilbestrol (DES) can developmentally imprint genes by changing the pattern of DNA methylation. We further discuss the implications of this and other findings for non-mutagenic aspects of developmental toxicology, and suggest ways to use this concept in modifying in vitro screening for developmental toxicants.