Comparative mapping of cloned human and murine antithyroglobulin antibodies: recognition by human antibodies of an immunodominant region

Antibodies (Ab) to thyroglobulin (Tg) are common in patients with autoimmune thyroid diseases, but it is currently unclear how Tg Ab are involved in the pathology of autoimmune thyroid disease. We have previously reported the isolation of immunoglobulin G (IgG)kappa and IgGlambda Fab from phage display combinatorial libraries from the cervical lymph node of a single Hashimoto's thyroiditis patient with a high anti-Tg titer. Sequence analysis of these Fab indicated a restricted heavy chain usage with a nonrestricted light chain usage, with Fab inhibiting the binding of patient Tg Ab by between 39% and 79%. Comparative mapping of nine each of these IgGkappa and IgGlambda Fab, and the patient serum from whom the Fab were derived, is described here, using a panel of 10 murine monoclonal antibodies (Mab) to human thyroglobulin (hTg). The Fab interacted principally with mAb defining the overlapping antigenic domains I and IV, previously characterized as the region recognized by the majority of patient serum Tg Ab. Tg Ab from serum of the patient from whom the Fab were derived were also directed at this region, suggesting that the Fab are representative of the Tg Ab present in this patient.     

Drug-drug interactions in pediatric psychopharmacology

Serious consequences caused by drug-drug interactions continue to plague contemporary pharmacotherapy. The possibility of a drug-drug interaction should be suspected anytime a new or unexpected effect occurs that complicates the clinical management of a patient in the setting where the patient is receiving more than one drug. In this article, the authors address the mechanisms of pharmacokinetic-based drug-drug interactions focusing on important interactions that may occur with the common medications a pediatrician may prescribe to the child receiving psychoactive medication(s) prescribed by a child psychiatrist.     

Role of cardiac troponin I in the evaluation of myocardial injury

Congenital fibrosarcoma is a rare soft tissue sarcoma. A 22-year-old woman in the 22nd week of her first pregnancy underwent sonographic examination, which revealed a soft tissue swelling of the fetus's left thigh. The pregnancy was terminated, and congenital fibrosarcoma was diagnosed by pathologic examination. To our knowledge, this is the first published report of the intrauterine sonographic observation of this tumor in a fetal extremity.     

Restrictive dermopathy. Report of 12 cases. Dutch Task Force on Genodermatology

BACKGROUND: This study describes 12 cases of restrictive dermopathy seen during a period of 8 years by the Dutch Task Force on Genodermatology. We present these unique consecutive cases to provide more insight into the clinical picture and pathogenesis of the disease. OBSERVATIONS: Clinical features in more than 85% of these children were prematurity, fixed facial expression, micrognathia, mouth in O position, rigid and tense skin with erosions and denudations, and multiple joint contractures. Ten patients underwent histopathologic skin biopsy. The biopsy results showed flattening of rete ridges in all 10 patients, a thin dermis with collagen aligned parallel to the epidermis in 9 patients, and poorly developed dermal appendages in 9 patients. Additional findings in individual patients included blepharophimosis, inguinal skin tear, skin tear in the frontal neck area that developed during delivery, absent eyelashes, a wide ascendent aorta, and dextrocardia. Fibroblast cultures taken from 5 patients did not show abnormal alpha 2 beta 1 and alpha 1 beta 1 integrin expressions. CONCLUSIONS: The alleged rarity of restrictive dermopathy may be partially caused by medical unfamiliarity with this entity, despite its characteristic clinical and histopathologic picture. The pathogenesis of the disease still needs to be elucidated.     

Excess of hMLH1 germline mutations in Swiss families with hereditary non-polyposis colorectal cancer

This article describes a high-performance liquid chromatographic (HPLC) method for the measurement of azithromycin (AZI) and two of its metabolites, 9a-N-desmethylazithromycin (ADES) and N-desmethylazithromycin (NDES), in human tears and plasma. The drug, metabolites, and internal standard (n-propylazithromycin [IS]) were detected electrochemically after injection of the extracted sample into the HPLC system. The peak height ratio (AZI, ADES, or NDES to IS) varied linearly, with concentrations in the ranges of 0.1 mg/L to 2.0 mg/L (tears) and 0.01 mg/L to 2.0 mg/L (plasma) of AZI, ADES, and NDES; the correlation coefficient (r) was more than 0.994 mg/L for all of the compounds (n=6). The analysis of tear samples collected at different intervals within 12 hours to 144 hours after a dose of 20 mg/kg of AZI from a trachoma patient yielded concentrations ranging from 1.52 mg/L to 0.34 mg/L for AZI, 0.79 mg/L to 0.27 mg/L for ADES, and 1.99 mg/L to less than 0.20 mg/L for NDES. The concentration of AZI in plasma ranged from 0.15 mg/L to 0.01 mg/L, whereas ADES and NDES were undetectable.     

Meloxicam inhibits the growth of colorectal cancer cells

Cyclooxygenase-2 has been reported to play an important role in colorectal carcinogenesis. The effects of meloxicam (a COX-2 inhibitor) on the growth of two colon cancer cell lines that express COX-2 (HCA-7 and Moser-S) and a COX-2 negative cell line (HCT-116) were evaluated. The growth rate of these cells was measured following treatment with meloxicam. HCA-7 and Moser-S colony size were significantly reduced following treatment with meloxicam; however, there was no significant change in HCT-116 colony size with treatment. In vivo studies were performed to evaluate the effect of meloxicam on the growth of HCA-7 cells when xenografted into nude mice. We observed a 51% reduction in tumor size after 4 weeks of treatment. Analysis of COX-1 and COX-2 protein levels in HCA-7 tumor lysates revealed a slight decrease in COX-2 expression levels in tumors taken from mice treated with meloxicam and no detectable COX-1 expression. Here we report that meloxicam significantly inhibited HCA-7 colony and tumor growth but had no effect on the growth of the COX-2 negative HCT-116 cells.     

Experimental study for the evaluation of creep in concrete through thermal measurements

This investigation, conducted at the Non-Destructive Testing Laboratory at the Politecnico di Torino, made it possible to establish an experimental relationship between specific creep values measured in concrete test pieces obtained from different mixes and the decrease in temperature observed in identical test pieces at the end of low-intensity short-duration compressive tests.This relationship is independent of type of mix and therefore has general validity: it can be used to make qualitative predictions about creep without having to perform long duration tests. It may lead to interesting developments in various applications, especially in the field of structural diagnosis.     

Sonic hedgehog signaling is essential for hair development

BACKGROUND: The skin is responsible for forming a variety of epidermal structures that differ amongst vertebrates. In each case the specific structure (for example scale, feather or hair) arises from an epidermal placode as a result of epithelial-mesenchymal interactions with the underlying dermal mesenchyme. Expression of members of the Wnt, Hedgehog and bone morphogenetic protein families (Wnt10b, Sonic hedgehog (Shh) and Bmp2/Bmp4, respectively) in the epidermis correlates with the initiation of hair follicle formation. Further, their expression continues into either the epidermally derived hair matrix which forms the hair itself, or the dermal papilla which is responsible for induction of the hair matrix. To address the role of Shh in the hair follicle, we have examined Shh null mutant mice. RESULTS: We found that follicle development in the Shh mutant embryo arrested after the initial epidermal-dermal interactions that lead to the formation of a dermal papilla anlage and ingrowth of the epidermis. Wnt10b, Bmp2 and Bmp4 continued to be expressed at this time, however. When grafted to nude mice (which lack T cells), Shh mutant skin gave rise to large abnormal follicles containing a small dermal papilla. Although these follicles showed high rates of proliferation and some differentiation of hair matrix cells into hair-shaft-like material, no hair was formed. CONCLUSIONS: Shh signaling is not required for initiating hair follicle development. Shh signaling is essential, however, for controlling ingrowth and morphogenesis of the hair follicle.