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1.
Attention deficit hyperactivity disorder (ADHD) is a prevalent psychiatric condition in children and follow up studies have indicated that 22-33% of patients continue to suffer from ADHD during late adolescence and adulthood. Convincing evidence supports the contribution of genetic factors in the etiology of ADHD, and the interaction of the psychostimulants with the dopamine system suggests that dopamine is involved in the pathophysiology. The 7-repeat allele of the 48 base pair repeat of the dopamine D4 receptor gene (DRD4) has been reported, with several replications, to be associated with ADHD in children. We tested for the presence of association between the DRD4 48 base repeat and adult ADHD in two independent samples: one comprised of cases and ethnically matched controls, and the second made up of nuclear families. Each case was assessed using a battery of adult ADHD assessment instruments. The analysis of the 66 cases and 66 controls showed a significantly higher presence of the 7-repeat in the adult ADHD patients vs. controls (chi(2) = 5.65; df = 1; P = 0.01). In the analysis of transmission of DRD4 alleles in 44 nuclear families with the transmission disequilibrium test, a trend was observed toward a increased transmission of the 7-repeat from the heterozygous parents to the affected offspring (chi(2) = 2.00; df = 1; P = 0.15). When the two samples were combined, the overall significance was stronger (N = 110; z = 2.68; P = 0.003). The results of our study suggest a role of the 7-repeat allele in adult subjects suffering from ADHD. This finding is an important continuation of the group of studies that together strongly suggest the involvement of DRD4 in ADHD. 相似文献
2.
Mancuso M Conforti FL Rocchi A Tessitore A Muglia M Tedeschi G Panza D Monsurrò M Sola P Mandrioli J Choub A DelCorona A Manca ML Mazzei R Sprovieri T Filosto M Salviati A Valentino P Bono F Caracciolo M Simone IL La Bella V Majorana G Siciliano G Murri L Quattrone A 《Neuroscience letters》2004,371(2-3):158-162
Mitochondrial impairment has been implicated in the pathogenesis of the amyotrophic lateral sclerosis (ALS). Furthermore, mitochondrial-specific polymorphisms were previously related to other neurodegenerative diseases, such as Parkinson, Friedreich and Alzheimer disease. To investigate if specific genetic polymorphisms within the mitochondrial genome (mtDNA) could act as susceptibility factors and contribute to the clinical expression of sporadic ALS (sALS), we have genotyped predefined European mtDNA haplogroups in 222 Italian patients with sALS and 151 matched controls. Individuals classified as haplogroup I demonstrated a significant decrease in risk of ALS versus individuals carrying the most common haplogroup, H (odds ratio 0.08, 95% confidence interval 0.04-0.4, p < 0.01). Further stratification of the dataset by sex, age and site of onset of disease and survival failed to reach significance for association. Our study provides evidence of the contribution of mitochondrial variation to the risk of ALS development in Caucasians. Further it may help elucidate the mechanism of the mitochondrial dysfunction detectable in ALS, and may be of relevance in development of strategies for the treatment of this disease. 相似文献
3.
Valeria Masciullo Tommaso Susini Alessandra Zamparelli Alessandro Bovicelli Corrado Minimo Daniela Massi Gianluigi Taddei Nicola Maggiano Pierandrea De Iaco Marcello Ceccaroni Luciano Bovicelli Gianni Amunni Salvatore Mancuso Giovanni Scambia Antonio Giordano 《Clinical cancer research》2003,9(14):5332-5338
PURPOSE: p27(Kip1) is a member of the Cip1/Kip1 family of cyclin-dependent kinase inhibitors and is a potential tumor suppressor gene. Low levels of p27 are associated with poor prognosis in a variety of gynecological tumors, including breast, ovarian, and cervical carcinomas. The role of p27 in endometrial cancer remains controversial. EXPERIMENTAL DESIGN: In the present study, p27 protein expression was investigated by immunohistochemistry in a series of 217 endometrial adenocarcinomas and, where present, in synchronous normal endometrium, simple and complex hyperplasia (with or without atypia), and cystic atrophy. The relationship between p27 expression and clinical outcome was also evaluated. RESULTS: Immunohistochemical analysis revealed a significant loss of p27 expression from normal (33%) through hyperplastic endometrium (50%) to endometrial adenocarcinomas (71%; P = 0.001). In addition to nuclear staining, cytoplasmic localization of p27 was noted in 193 (91%) of 217 specimens examined. When the clinical outcome of the patients was evaluated in relation to p27 status, we found no significant correlation between the presence of p27 staining and clinicopathological parameters or survival. CONCLUSIONS: These data indicate that p27 expression could progressively decrease from normal endometrium through hyperplastic endometrium to invasive endometrial carcinomas, suggesting that loss of this tumor suppressor may represent a novel and distinct molecular alteration involved in estrogen-related endometrial adenocarcinomas (type I). Despite the suggested role of the p27 protein in determining the prognosis of several human tumors, it was not found to be a predictor of clinical outcome in this large group of patients with endometrial cancer. 相似文献
4.
Federica Medici Stefania Rizzo Milly Buwenge Alessandra Arcelli Martina Ferioli Gabriella Macchia Francesco Deodato Savino Cilla Pierandrea De Iaco Anna Myriam Perrone Silvia Strolin Lidia Strigari Gloria Ravegnini Alberto Bazzocchi Alessio G. Morganti 《Current oncology (Toronto, Ont.)》2022,29(11):8513
Sarcopenia (SP) is a syndrome characterized by age-associated loss of skeletal muscle mass and function. SP worsens both acute and late radiation-induced toxicity, prognosis, and quality of life. Myosteatosis is a pathological infiltration of muscle tissue by adipose tissue which often precedes SP and has a proven correlation with prognosis in cancer patients. Sarcopenic obesity is considered a “hidden form” of SP (due to large fat mass) and is independently related to higher mortality and worse complications after surgery and systemic treatments with worse prognostic impact compared to SP alone. The evaluation of SP is commonly based on CT images at the level of the middle of the third lumbar vertebra. On this scan, all muscle structures are contoured and then the outlined surface area is calculated. Several studies reported a negative impact of SP on overall survival in patients undergoing RT for tumors of the head and neck, esophagus, rectum, pancreas, cervix, and lung. Furthermore, several appetite-reducing side effects of RT, along with more complex radiation-induced mechanisms, can lead to SP through, but not limited to, reduced nutrition. In particular, in pediatric patients, total body irradiation was associated with the onset of SP and other changes in body composition leading to an increased risk of cardiometabolic morbidity in surviving adults. Finally, some preliminary studies showed the possibility of effectively treating SP and preventing the worsening of SP during RT. Future studies should be able to provide information on how to prevent and manage SP before, during, or after RT, in both adult and pediatric patients. 相似文献
5.
Lindsay Kennedy Parrish Louis J. Muglia 《The journal of maternal-fetal & neonatal medicine》2019,32(1):73-79
Purpose: the purpose of this study is to identify risk factors for familial, likely genetically-determined, preterm birth.Materials and methods: We performed a case–control study, enrolling 211 patients (103 cases and 108 controls). Cases delivered between 20 and 35 weeks gestation, with a prior preterm birth or first-degree relative born prematurely. Controls delivered between 37–42 weeks. Groups were compared using a comprehensive questionnaire validated by medical record. Multivariate logistic regression assessed risk factor associations.Results: Of cases, 30% reported bleeding during pregnancy compared with 5% of controls, adjusted odds ratio (adjOR) 9.0, 95%CI 3.31–24.47. Of cases that delivered at 20–28 weeks, 44.8% reported bleeding during pregnancy compared with 24.6% at 29–35 weeks, p?=?.04. Other associations were prior first-trimester miscarriage adjOR 2.55 (CI 1.21–5.35) or second-trimester miscarriage, adjOR 6.3 (CI 1.76–22.56).Conclusions: Bleeding during pregnancy and prior miscarriage were significantly associated with familial preterm birth. The magnitude of effect for bleeding in pregnancy was higher with earlier preterm births. These associations warrant further investigation. 相似文献
6.
Melinda G Arnett Lisa M Muglia Gloria Laryea Louis J Muglia 《Neuropsychopharmacology》2016,41(1):245-260
The normal function of the hypothalamic-pituitary-adrenal (HPA) axis, and resultant glucocorticoid (GC) secretion, is essential for human health. Disruption of GC regulation is associated with pathologic, psychological, and physiological disease states such as depression, post-traumatic stress disorder, hypertension, diabetes, and osteopenia, among others. As such, understanding the mechanisms by which HPA output is tightly regulated in its responses to environmental stressors and circadian cues has been an active area of investigation for decades. Over the last 20 years, however, advances in gene targeting and genome modification in rodent models have allowed the detailed dissection of roles for key molecular mediators and brain regions responsible for this control in vivo to emerge. Here, we summarize work done to elucidate the function of critical neuropeptide systems, GC-signaling targets, and inflammation-associated pathways in HPA axis regulation and behavior, and highlight areas for future investigation. 相似文献
7.
Duplex Doppler sonography of transplant renal artery stenosis 总被引:7,自引:0,他引:7
de Morais RH Muglia VF Mamere AE Garcia Pisi T Saber LT Muglia VA Elias J Piccinato CE Trad CS 《Journal of clinical ultrasound : JCU》2003,31(3):135-141
PURPOSE: The aim of this study was to evaluate the accuracy of duplex Doppler sonography in diagnosing transplant renal artery stenosis (TRAS) and to determine which parameter is the most reliable for making that diagnosis. METHODS: Over a 3-year period, we sonographically evaluated patients who were referred for investigation of possible TRAS. We investigated the following parameters: peak systolic velocity (PSV) in the external iliac and renal arteries, acceleration time and acceleration in the intrarenal arteries, acceleration time in the renal artery, resistance index, and the ratio of the PSVs in the renal and external iliac arteries. We also used MR angiography and digital subtraction arteriography to verify the degree of stenosis. After the evaluations, the patients were classified into 2 groups, 1 with and the other without significant stenosis (> 50% narrowing of the lumen) on digital subtraction arteriography. We also included a control group of patients who had undergone renal transplantation at least 6 months before, had had a good course after transplantation, had a diastolic blood pressure of 90 mm Hg or less, and were taking a maximum of 1 antihypertensive drug. RESULTS: Our study population consisted of 22 patients suspected to have TRAS (10 without and 12 with confirmed significant stenosis) and 19 control patients. We found statistically significant differences between the mean values of these 3 groups except for the PSV in the iliac artery and the resistance index in the intrarenal arteries. The most accurate parameters to use in diagnosing TRAS were an acceleration time of 0.1 second or higher in the renal and intrarenal arteries, a PSV of greater than 200 cm/second in the renal artery, and a ratio of PSVs in the renal and external iliac arteries of greater than 1.8. CONCLUSIONS: Duplex Doppler sonography is an excellent method for screening patients suspected to have TRAS and can help select which of those patients should undergo digital subtraction arteriography. 相似文献
8.
Ann Martin MDa Elsa Gutierrez MDa Jennie Muglia MDb Charles J. McDonald MDb Cynthia Guzzo MDc Alice Gottlieb MD PhDd Amy Pappert MDd W.Thomas Garland MDe Jerry Bagel MDf Patricia Bacha PhDg 《Journal of the American Academy of Dermatology》2001,45(6):871
Background: Denileukin diftitox, a fusion protein targeting both malignant and normal activated lymphocytes, has been shown previously to have antipsoriatic activity. However, the ideal dosing regimen for treating psoriasis was not established. Objective: We examined the safety and efficacy of denileukin diftitox in patients with severe plaque-type psoriasis. Methods: This was a cohort dose-escalation trial. Patients were administered denileukin diftitox on 3 consecutive days every other week. Patients were evaluated for toxicity, improvement in psoriasis, immunogenicity, and serum levels. Results: Thirty-five patients were treated at 3 dose levels. Eight patients had a 50% decrease or more in Psoriasis Area and Severity Index score from baseline (0/10 at 0.5 μg/kg per day, 1/10 at 1.5 μg/kg per day, and 7/15 at 5 μg/kg per day). Adverse events primarily consisted of constitutional events and skin reactions. Conclusions: The potential antipsoriatic activity of denileukin diftitox demonstrated in this study was comparable to that observed in other psoriasis studies with this agent. However, this dosing regimen was better tolerated than the dosing regimen used in the last study with denileukin diftitox in psoriasis patients. (J Am Acad Dermatol 2001;45:871-81.) 相似文献
9.
Corticotropin-releasing hormone (CRH)-deficient (knockout (KO)) mice demonstrate severely impaired adrenal responses to restraint, ether, and fasting, and lack the normal diurnal glucocorticoid (GC) rhythm. Here, we summarize recent studies determining the role of CRH in augmenting plasma adrenocorticotrophic hormone (ACTH) concentration after glucocorticoid withdrawal and pituitary-adrenal axis stimulation in the context of inflammation. Even though GC insufficient, basal pituitary proopiomelanocortin (POMC) mRNA, ACTH peptide content within the pituitary, and plasma ACTH concentrations are not elevated in CRH KO mice. POMC mRNA content in CRH KO mice increases following adrenalectomy, and this increase is reversed by GC, but not aldosterone, replacement. In marked contrast to the increase in POMC mRNA, plasma ACTH does not increase in the CRH KO mice following adrenalectomy. Administration of CRH to adrenalectomized CRH KO mice results in acute, robust ACTH secretion. Thus, loss of GC feedback can increase POMC gene expression in the pituitary, but CRH action is essential for increased secretion of ACTH into the circulation. While GC secretion is impaired in CRH KO mice after most stimuli, we have found near-normal GC responses to inflammation and systemic immune challenge. Studies in mice with CRH and IL-6 deficiency reveal that IL-6 is essential for activation of the pituitary-adrenal axis during inflammatory and other stressors in the absence of CRH. 相似文献
10.
Bielinska M Parviainen H Porter-Tinge SB Kiiveri S Genova E Rahman N Huhtaniemi IT Muglia LJ Heikinheimo M Wilson DB 《Endocrinology》2003,144(9):4123-4133