Examination of joint space by magnetic resonance imaging in anatomically normal knees

The medial and lateral knee joint spaces of 184 patients who had anatomically normal knees were measured by using magnetic resonance imaging (MRI) method. The findings were compared according to age, sex, height, and body mass index changes of the individuals and the mean values of medial and lateral knee joint spaces were calculated in every group. The results show that in an anatomically normal population, all the individuals have larger lateral knee joint spaces than medial knee joint spaces. The patients lose knee joint space regularly with increasing age. Children have larger knee joint spaces than adults. Men have larger knee joint spaces than women. The knee joint space size of the patients increase regularly with increasing height up to 180 cm. The patients, who are taller than 180 cm do not show any marked difference in joint space size, when compared with the patients whose heights differ in between 171–180 cm. Knee joint space size is not related to the body mass index of the individual. © 1996 Wiley-Liss, Inc.     

Specific mosaic KRAS mutations affecting codon 146 cause oculoectodermal syndrome and encephalocraniocutaneous lipomatosis

Oculoectodermal syndrome (OES) and encephalocraniocutaneous lipomatosis (ECCL) are rare disorders that share many common features, such as epibulbar dermoids, aplasia cutis congenita, pigmentary changes following Blaschko lines, bony tumor‐like lesions, and others. About 20 cases with OES and more than 50 patients with ECCL have been reported. Both diseases were proposed to represent mosaic disorders, but only very recently whole‐genome sequencing has led to the identification of somatic KRAS mutations, p.Leu19Phe and p.Gly13Asp, in affected tissue from two individuals with OES. Here we report the results of molecular genetic studies in three patients with OES and one with ECCL. In all four cases, Sanger sequencing of the KRAS gene in DNA from lesional tissue detected mutations affecting codon 146 (p.Ala146Val, p.Ala146Thr) at variable levels of mosaicism. Our findings thus corroborate the evidence of OES being a mosaic RASopathy and confirm the common etiology of OES and ECCL. KRAS codon 146 mutations, as well as the previously reported OES‐associated alterations, are known oncogenic KRAS mutations with distinct functional consequences. Considering the phenotype and genotype spectrum of mosaic RASopathies, these findings suggest that the wide phenotypic variability does not only depend on the tissue distribution but also on the specific genotype.     

Preparation and in vivo evaluation of novel linkers for 211At labeling of proteins

The syntheses, radiolabeling, antibody conjugation and in vivo evaluation of new linkers for (211)At labeling of monoclonal antibodies are described. Syntheses of the N-succinimidyl esters and labeling with (211)At to form succinimidyl 4-methoxymethyl-3-[(211)At]astatobenzoate (9) and succinimidyl 4-methylthiomethyl-3-[(211)At]astatobenzoate (11) from the corresponding bromo-aryl esters is reported. Previously reported succinimidyl N-{4-[(211)At]astatophenethyl}succinamate (SAPS) is employed as a standard of in vivo stability. Each agent is conjugated with Herceptin in parallel with their respective (125)I analogue, succinimidyl 4-methoxymethyl-3-[(125)I]iodobenzoate (10), succinimidyl 4-methylthiomethyl-3-[(125)I]iodobenzoate (12) and succinimidyl N-{4-[(125)I]iodophenethyl}succinamate (SIPS), respectively, for comparative assessment in LS-174T xenograft-bearing mice. With 9 and 11, inclusion of an electron pair donor in the ortho position does not appear to provide in vivo stability comparable to SAPS. Variables in radiolabeling chemistry of these three agents with (211)At are notable. Sequential elimination of acetic acid and oxidizing agent, N-chlorosuccinimide (NCS), from the (211)At radiolabeling protocol for forming SAPS improves yield, product purity and consistency. NCS appears to be critical for the radiolabeling of 6 with (211)At. Formation of 11, however, is found to require the absence of NCS. Elimination of acetic acid is found to have no effect on radiolabeling efficiency or yield for either of these reactions.     

FTO mRNA Expression in Extremely Obese and Type 2 Diabetic Human Omental and Subcutaneous Adipose Tissues

Background

Fat mass and obesity-associated protein (FTO) gene expression is known to correlate with obesity. Our aim was to investigate the FTO gene expression in paired omental and subcutaneous human adipose tissues from morbid and obese patients. To understand the role of CD68-positive macrophages in adipose tissues, the correlation with adiposity parameters such as adipocyte diameter and adipocyte radius was also measured. Drug and adiposity correlations were also analyzed.

Methods

Paired omental and subcutaneous adipose tissue were excised during elective surgery from morbidly obese (n?=?9) and obese (n?=?5) patients. FTO expressions were determined by quantitative PCR. Tissue sections were analyzed for their CD68 protein expressions by immunuhistochemistry.

Results

Omental and subcutaneous adipose tissue FTO gene expression levels were not found to differ significantly among morbidly obese and obese study groups. Serum aspartate aminotransferase e and alanine transaminase levels were found to be in negative correlation with subcutaneous fat tissue FTO expression rate. Antidiabetic drug use was found to be in correlation with adiposity. Both subcutaneous and omental fat cell diameters were found to have correlation with antidiabetic drug use. Omental fat cell diameter was found to enlarge together with omental CD68 protein expression. Subcutaneous macrophage number decreased while omental fat cell radius increased. Omental macrophage number was found in correlation with subcutaneous macrophage number.

Conclusions

Antidiabetic therapy was found to increase adiposity in omental and subcutaneous fat. Further research is needed with larger samples to explore the exact role of FTO in obesity.     

High responders are not exempt from detrimental effects of prematurely rising progesterone levels in fresh embryo transfer cycles

Research question

Are high-responder IVF patients protected from the deleterious effect of prematurely elevated serum progesterone level on the probability of pregnancy?

Increased expression of epidermal growth factor receptors in the tracheal epithelia after topical mitomycin-C in rabbits

The aim is to examine histopathological changes and expression of epidermal growth factor receptor (EGFR) in tracheal epithelia caused by application of topical mitomycin-C (MMC) in rabbit model after the tracheotomy procedure. The conventional tracheotomy was performed in 16 rabbits. They were randomly divided into two equal groups. The first group was applied MMC at a concentration of 0.4 mg/ml around tracheotomy for 5 min, and the other group was not taken a treatment as a control. The animals were sacrificed at the end of 4 weeks. Their tracheas were evaluated with H&E and Masson's trichrome histochemically, and with antiepidermal growth factor receptor immunohistochemically. Results showed that there was no significant difference between MMC and control group for inflammatory cells (P=0.09). The numbers of fibroblasts and subepithelial tissue thickness in the group exposed to MMC were significantly lower than the control group (P<0.05). In contrast, the percentage of EGFR in the application of MMC group was significantly higher than the control group (P<0.05). The application of topical MMC on airway epithelia after tracheotomy showed significant elevation in the levels of epithelial EGFR expression compared to controls in a rabbit model. The activation of epithelial EGFR may facilitate epithelial healing, but further studies are needed to assess the effect of topical MMC on respiratory epithelia.