Minireview: structural and functional evolution of the thyrotropin receptor

TSH receptor (TSHR) is a member of the leucine-rich repeat-containing G protein-coupled receptors. Both TSHR and its ligand TSH have evolved to acquire specificity, minimize cross-reaction to other glycoprotein hormone receptors, and modulate cognate interaction (and thereby thyrotropic activity). TSHR sequences available from two life orders, teleost and mammals, were analyzed. Teleost TSHRs with low affinity are expressed in many nonthyroidal tissues and show a tendency to gene duplication. In some teleosts, TSHR has limited specificity, and in others extremely high constitutive activity, suggesting the possibility of ligand-independent receptor function. Although mammalian TSHR, in contrast to other glycoprotein hormone receptors, maintains relatively high constitutive activity, the thyrotropic activity of TSH appears to decline in hominoids including humans, probably as part of metabolic adaptation to the changing environment. Critical TSHR residues that determine hormone specificity have been identified in the leucine-rich repeats, and others within the cysteine-rich C-flanking region that determines hormonal activation as well as receptor silencing. Transmembrane (TM) helices, particularly the TM5 and TM6, are likely involved in receptor homodimerization and a unique motif in TM7 appears essential to receptor silencing and internalization. Surprisingly, ternary structures in the intracellular domain as opposed to specific sequence motifs are critical for intracellular TSHR trafficking. It is evident that progress in understanding structure-function relationships of TSHR and its ligand can be further stimulated by inclusion of evolutionary analysis of their primary, secondary and tertiary structure. Such an integrated approach should also contribute to the rational design of highly efficacious therapeutics with either agonistic or antagonistic properties.     

Prevalence of Hepatic Granulomas in Chronic Hepatitis B

An increasing frequency of hepatic granulomas, up to 10%, in chronic hepatitis C patients is reported, and their presence is considered to be a predictor of treatment success. However, there is only one prevalence study on granuloma in chronic hepatitis B, and its significance for treatment outcome is unknown. We aimed to determine the prevalence of hepatic granulomas in a larger group of chronic hepatitis B patients and to compare their presence with the response to interferon therapy. Biopsy specimens of chronic hepatitis B patients were reevaluated for the presence of hepatic granulomas. All patients with hepatic granuloma were screened for other granulomatous diseases by tuberculin skin test, chest X-ray and computed tomography, venereal disease research laboratory, Brucella agglutination tests, and exposure to hepatotoxic agents. We screened 663 cases of chronic hepatitis B. Hepatic granulomas were found in 10 cases (1.5%). The granulomas could not be ascribed to any other reason. Of the 10 patients with hepatic granulomas, 4 responded to interferon therapy, 2 dropped out, and 4 were nonresponders. We conclude that hepatic granuloma is a rare finding in chronic hepatitis B and its presence does not seem to predict the response to interferon therapy.     

What Happens at the Adjacent Knee Joint After Total Hip Arthroplasty of Crowe Type III and IV Dysplastic Hips?

We prospectively evaluated 30 hips of 22 patients who had normal knees with a mean age of 53.4 years (range, 38-72 years). In the early postoperative period, genu valgum deformity was observed in all knees. Of 22 patients, 17 complained of severe pain owing to strain in the medial collateral ligament and iliotibial tract. Postoperatively, the ipsilateral extremities of the patients were extended by a mean of 16.5 mm (8-25 mm). Q angles of the patients increased by a mean of 4.4° ± 2.5° (P < .001). Although the Harris hip scores were improved (40.7-87.8 points), postoperative Lysholm-Gillquist knee scores were significantly reduced (92-76 points, P < .001). Reduction of displaced hips into the anatomical hip center and lengthening the extremity despite shortening procedure may lead to strain at the knee joint iatrogenically, particularly with the mechanical effect of tensor fascia lata, which results with changes in the knee biomechanics.     

Leptin,ghrelin and calprotectin: inflammatory markers in childhood asthma?

Background

Appetite-modulating hormones ghrelin and leptin might be relevant to asthma with their pro-inflammatory effects, and calprotectin has been recognized as a promising marker of inflammation. The purpose of this study was to explore whether asthma, atopy and lung functions has a relation with serum levels of leptin, ghrelin and calprotectin as inflammatory markers in children.

Methods

A cross-sectional study was performed by searching the doctor diagnosed asthma through questionnaires filled in by parents who were phoned, and children were invited to supply fasting blood samples in order to measure serum levels of leptin, ghrelin and calprotectin, and to perform skin prick test and spirometry. Participants were divided into Group 1, children with previous diagnosis of asthma, and Group 2, children without previous diagnosis of asthma.

Results

One thousand and two hundred questionnaires were distributed and 589 of them were returned filled in. Out of 74 children whose parents accepted to participate in the study, 23 were in Group 1 and 51 were in Group 2. There was no statistical difference in serum levels of leptin, ghrelin, calprotectin, forced expiratory volume in one second (FEV₁₎, forced vital capacity (FVC), peak expiratory flow (PEF) , forced expiratory flow between 25 and 75% of vital capacity (FEF_25-75) values , and skin prick test results between the two groups (p values are 0.39, 0.72, 0.5, 0.17, 0.5, 0.27, 0.18, and 0.81 respectively).

Conclusion

In this study the inflammation in asthmatic children could not be shown by using serum leptin, ghrelin and calprotectin levels and this is possibly due to the low number of children with ever asthma and equal skin prick test positivity in both groups. This study is the first study aimed to show the relation between serum calprotectin levels and inflammation in asthma. As this study was a cross-sectional study, further prospectively designed randomized controlled studies are necessary to show the association of these markers and inflammation in asthma.

     

No association between DUP25 and anxiety disorders.

Gratacos et al. [2001: Cell 106:367-379] described an interstitial duplication dup(15)q24q26 (DUP25) in patients with anxiety disorders; this duplication was found in approximately 90% of patients and in 7% of controls. In order to determine if DUP25 is present in additional individuals susceptible to panic attacks, we tested 44 patients with anxiety disorders, using probes 251c23 and 216c14 mapping in the 15q24 and 15q26 region. We have not detected any DUP25. Our results suggest that DUP25 is not common in people with anxiety disorders in the population tested here.     

The state of leucocyte adhesiveness/aggregation in the peripheral blood: A new and independent marker of mental stress

A direct slide test was used to detect the presence of aggregated white blood cells in the peripheral blood. By this means the state of leucocyte adhesiveness/aggregation (LAA) during acute mental stress was determined in 22 healthy volunteers and compared to the white blood cell count (WBCC). The LAA test proved to be more sensitive (73 per cent) as compared to the WBCC (40 per cent). This increased sensitivity is a result of a greater deviation of the LAA from normal values (obtained in 22 healthy controls) than the one obtained in the absolute cell number in the circulating pool. It is assumed that factors released during stress induce a state of increased LAA. Hence the determination of the adhesive state together with the absolute WBCC may yield a rapid, cheap and efficient laboratory criterion for the detection of mental stress.