Search results for "ARFI"
showing 10 items of 103 documents
Identification of noncovalent proteasome inhibitors with high selectivity for chymotrypsin-like activity by a multistep structure-based virtual scree…
2016
Noncovalent proteasome inhibitors introduce an alternative mechanism of inhibition to that of covalent inhibitors, e.g. carfilzomib, used in cancer therapy. A multistep hierarchical structure-based virtual screening (SBVS) of the 65,375 NCI lead-like compound library led to the identification of two compounds (9 and 28) which noncovalently inhibited the chymotrypsin-like (ChT-L) activity (Ki = 2.18 and 2.12 μM, respectively) with little or no effects on the other two major proteasome proteolytic activities, trypsin-like (T-L) and post-glutamyl peptide hydrolase (PGPH) activities. A subsequent hierarchical similarity search over the full NCI database with the most active tripeptide-based inh…
Estimating the dwarfing rate of an extinct Sicilian elephant.
2021
Summary Evolution on islands, together with the often extreme phenotypic changes associated with it, has attracted much interest from evolutionary biologists. However, measuring the rate of change of phenotypic traits of extinct animals can be challenging, in part due to the incompleteness of the fossil record. Here, we use combined molecular and fossil evidence to define the minimum and maximum rate of dwarfing in an extinct Mediterranean dwarf elephant from Puntali Cave (Sicily). 1 Despite the challenges associated with recovering ancient DNA from warm climates, 2 we successfully retrieved a mitogenome from a sample with an estimated age between 175,500 and 50,000 years. Our results sugge…
The visceral adiposity index is associated with insulin sensitivity and IGF-I levels in adults with growth hormone deficiency
2016
The visceral adiposity index, based on anthropometric and metabolic parameters, has been shown to be related to adipose tissue function and insulin sensitivity. We aimed to evaluate the performance of the visceral adiposity index in adult patients with growth hormone deficiency. We enrolled 52 patients(mean age 51 ± 13 years) with newly diagnosed growth hormone deficiency and 50 matched healthy subjects as controls at baseline. At baseline and after 12 and 24 months of treatment we evaluated anthropometric measures, lipid profile, glucose and insulin during an oral glucose tolerance test, hemoglobin A1c, homeostasis model assessment estimate of insulin resistance, quantitative insulin sensi…
Comparison of transient elastography and acoustic radiation force impulse for non-invasive staging of liver fibrosis in patients with chronic hepatit…
2011
Transient elastography (TE) is adequate for a diagnosis of cirrhosis, but its accuracy for milder stages of fibrosis is much less satisfactory. The objective of this study was to compare the performance and the discordance rate of acoustic radiation force impulse (ARFI) and TE with liver biopsy in a cohort of chronic hepatitis C (CHC) patients.One hundred thirty-nine consecutive patients with CHC were enrolled in two tertiary centers, and evaluated for histological (Metavir score) and biochemical features. All patients underwent TE and ARFI.TE was unreliable in nine patients (6.5%), while in no cases (0%) were ARFI invalid measurements recorded (P=0.029). By area under receiver operating ch…
HETEROGENEITY OF METATROPIC DYSPLASIA
1983
Metatropic dysplasia is a neonatally manifest entity that is characterized clinically by a rapidly progressing kyphoscoliosis leading to severe shortening of the originally long trunk ("metatropism"). Major radiographic features include flattening and defective ossification of the vertebral bodies, a narrow thorax and a marked hypoplasia of the basilar portions of the ilia with crescent-shaped iliac crests. There is some evidence of genetic heterogeneity. From five personal observations and from a review of the literature we conclude that metatropic dysplasia comprises at least three genetic entities: (1) a nonlethal type with autosomal recessive transmission; (2) a nonlethal dominant type …
Gender-, age- and time-dependent dosing of growth hormone in adults - real-world data from a decade of clinical practice in Germany.
2017
We evaluated treatment patterns and gender-dependent dosing of growth hormone (GH) substitution in adults with GH deficiency (AGHD). Data on GH dose were collected (2003-2013) from 509 GH-treated patients (mean age: 48.9 years; 47% female) enroled in the observational German NordiWin study (NCT01543880). The impact of gender, age, treatment duration and calendar year on GH treatment patterns was evaluated by multiple regression analysis. Mean (SD) baseline GH dose (mg/day) was similar between females (0.25 [0.19] and males (0.24 [0.15]), but increased with treatment duration (at year 10, 0.55 [0.48] and 0.31 [0.09] in females and males, respectively), reflecting patient dose titration. GH d…
Heterochronic differentiation of sexual dimorphs among Jurassic ammonite species
1997
Ontogenetic and then heterochronic approaches are used here to analyze sexual differentiation within two well-known Jurassic dimorphic species. This analysis compares two ways of determining the relative biological age of ammonites, one using size (diameter) and the other the number of septa as a proxy of age. The shape standard is established from factor analysis of morphological and growth parameters. Size-age-shape relationships are analyzed on the basis of a new heterochronic representation. When diameter is used as a proxy of age, microconch morphs are globally considered to be progenetic compared with macroconch morphs. When size and age are determined separately and shape is included…
The clinical and molecular spectrum of QRICH1 associated neurodevelopmental disorder
2022
De novo variants in QRICH1 (Glutamine-rich protein 1) has recently been reported in 11 individuals with intellectual disability. The function of QRICH1 is largely unknown but it is likely to play a key role in the unfolded response of endoplasmic reticulum (ER) stress through transcriptional control of proteostasis. In this study, we present 27 additional individuals and delineate the clinical and molecular spectrum of the individuals (n=38) with QRICH1 variants. The main clinical features were mild to moderate developmental delay/intellectual disability (71%), non-specific facial dysmorphism (92%) and hypotonia (39%). Additional findings included poor weight gain (29%), short stature (29%)…
Reduction in insulin sensitivity and inadequate β-cell capacity to counteract the increase in insulin resistance in children with idiopathic growth h…
2014
Purpose: To evaluate the performance of various indexes of insulin sensitivity and secretion and to identify the most useful indicator of deterioration of glucose metabolism in a cohort of children with growth hormone (GH) deficiency (GHD) during GH treatment. Methods: In 73 GHD children (55 M, 18 F; mean age 10.5 years) at baseline and after 12 months of treatment, we evaluated a number of surrogate indexes of insulin secretion and sensitivity. In a subgroup of 11 children we also performed an euglycemic hyperinsulinemic clamp. Results: After 12 months, a significant increase in fasting glucose (p < 0.001) and HbA1c levels (p < 0.001) was documented, despite all children remained with a no…
One-hour post-load plasma glucose level is associated with a worse metabolic profile in children with GH deficiency
2017
Purpose: In children, the plasma glucose value at 1 h (1hPG) during OGTT higher than 132.5 mg/dl is a predictor of alterations in glucose metabolism. We aimed to metabolically characterize GHD children according to 1hPG levels. Methods: Fifty-one GHD children (35 M, 16 F; mean age 8.6 years), grouped according to 1hPG, were evaluated at diagnosis and after 12 months of GH treatment (GHT) and compared with 50 matched controls at baseline. Auxological parameters, insulin-like growth factor-1 (IGF-1), glucose and insulin during OGTT, lipid profile, the oral disposition index (DIo), the homeostasis model assessment estimate of insulin resistance (Homa-IR), and the insulin sensitivity index (ISI…