Pituitary adenylate cyclase activating polypeptide as a novel hypophysiotropic factor in fish

Pituitary adenylate cyclase activating polypeptide (PACAP) is a novel member of the secretin-glucagon peptide family. In mammals, this peptide has been located in a wide range of tissues and is involved in a variety of biological functions. In lower vertebrates, especially fish, increasing evidence suggests that PACAP may function as a hypophysiotropic factor regulating pituitary hormone secretion. PACAP has been identified in the brain-pituitary axis of representative fish species. The molecular structure of fish PACAP is highly homologous to mammalian PACAP. The prepro-PACAP in fish, however, is distinct from that of mammals as it also contains the sequence of fish GHRH. In teleosts, the anterior pituitary is under direct innervation of the hypothalamus and PACAP nerve fibers have been identified in the pars distalis. Using the goldfish as a fish model, mRNA transcripts of PACAP receptors, namely the PAC1 and VPAC1 receptors, have been identified in the pituitary as well as in various brain areas. Consistent with the pituitary expression of PACAP receptors, PACAP analogs are effective in stimulating growth hormone (GH) and gonadotropin (GTH)-II secretion in the goldfish both in vivo and in vitro. The GH-releasing action of PACAP is mediated via pituitary PAC1 receptors coupled to the adenylate cyclase-cAMP-protein kinase A and phospholipase C-IP3-protein kinase C pathways. Subsequent stimulation of Ca 2+ entry through voltage-sensitive Ca 2+ channels followed by activation of Ca 2+-calmodulin protein kinase II is likely the downstream mechanism mediating PACAP-stimulated GH release in goldfish. Although the PACAP receptor subtype(s) and the associated post-receptor signaling events responsible for PACAP-stimulated GTH-II release have not been characterized in goldfish, these findings support the hypothesis that PACAP is produced in the hypothalamus and delivered to the anterior pituitary to regulate GH and GTH-II release in fish.published_or_final_versio

Interferon antibodies may negate the antiviral effects of recombinant α-interferon treatment in patients with chronic hepatitis B virus infection

In a randomized controlled trial of recombinant α-2a interferon for chronic hepatitis B, interferon antibodies developed in 21 (39%) of 54 Chinese adults who received IFN. No correlation was observed between sex, age, pretreatment serum ALT level or liver histological findings and the development of interferon antibodies. Antibodies were significantly more likely to develop in patients who received lower doses (2.5 or 5 MU/m2) of α-2a interferon than in those who received a higher dose (10 MU/m2): 53% vs. 11% (p = 0.006). The development of interferon antibodies appeared to reverse the initial antiviral response to treatment, with reappearance of hepatitis B virus DNA in serum in 12 patients and HBeAg in three patients. Sustained clearance of HBeAg was achieved in only one (5%) patient but was achieved in seven (21%) patients without interferon antibodies. The mere presence of interferon antibodies did not preclude an antiviral response to interferon therapy, but patients with high titer neutralizing antibodies were less likely to respond. These findings suggest that interferon antibodies may negate the antiviral effects of α-2a interferon. A higher incidence of interferon antibodies in Chinese vs. white patients with chronic hepatitis B may contribute to the poorer antiviral response in Chinese patients.link_to_subscribed_fulltex

Chinese Character Segmentation Strategies and the Use of Orthographic Knowledge: A Study on Ethnic Minority Adolescent CSL Learners

Purpose: The study investigates the character segmentation strategies and the use of orthographic knowledge of ethnic minority (EM) Chinese as a second language (CSL) learners (N=151) from a Hong Kong mainstream secondary school. Method: Grade 7 to 11 EM CSL learners of various ancestral origins, all native speakers of alphabetic languages without prior formal training on Chinese components and spatial configurations, were given a 26-question paper-and-pencil assessment test on the separation of Chinese components. The data collected was analyzed to their use of orthographic knowledge during the process of characters segmentation. Results: Five general character segmentation strategies were identified in this study, namely (1) agglomeration of components; (2) hybrid agglomeration of sequenced strokes and components; (3) arbitrary repetition of (parts of) component; (4) agglomeration of sequenced strokes; and (5) unanalytical agglomeration of strokes. The results show that there is a strong connection between character segmentation strategies of CSL learners and the learners’ use of orthographic knowledge. The high-scoring learners were able to discern components of varying levels in a character and segment them in an orderly sequence, whereas the low-scoring learners were unable to discern components but to arbitrarily segment characters as strokes in an orderly or disorderly sequence. Conclusions: An analysis of the results concludes that specific, feature-based perceptual training on Chinese orthographic knowledge, inclusive of character components and spatial configurations, is likely to enhance EM CSL learners’ ability to accurately recognize Chinese characters for effective decoding

Goldfish calmodulin: Molecular cloning, tissue distribution, and regulation of transcript expression in goldfish pituitary cells

Calmodulin (CaM) is a Ca2+-binding protein essential for biological functions mediated through Ca2+-dependent mechanisms. In the goldfish, CaM is involved in the signaling events mediating pituitary hormone secretion induced by hypothalamic factors. However, the structural identity of goldfish CaM has not been established, and the neuroendocrine mechanisms regulating CaM gene expression at the pituitary level are still unknown. Here we cloned the goldfish CaM and tested the hypothesis that pituitary expression of CaM transcripts can be the target of modulation by hypothalamic factors. Three goldfish CaM cDNAs, namely CaM-a, CaM-bS, and CaM-bL, were isolated by library screening. These cDNAs carry a 450-bp open reading frame encoding the same 149-amino acid CaM protein, the amino acid sequence of which is identical with that of mammals, birds, and amphibians and is highly homologous (≥90%) to that in invertebrates. In goldfish pituitary cells, activation of cAMP- or PKC-dependent pathways increased CaM mRNA levels, whereas the opposite was true for induction of Ca2+ entry. Basal levels of CaM mRNA was accentuated by GnRH and pituitary adenylate cyclase-activating polypeptide but suppressed by dopaminergic stimulation. Pharmacological studies using D1 and D2 analogs revealed that dopaminergic inhibition of CaM mRNA expression was mediated through pituitary D2 receptors. At the pituitary level, D2 activation was also effective in blocking GnRH- and pituitary adenylate cyclase-activating polypeptide-stimulated CaM mRNA expression. As a whole, the present study has confirmed that the molecular structure of CaM is highly conserved, and its mRNA expression at the pituitary level can be regulated by interactions among hypothalamic factors.link_to_subscribed_fulltex

How Ethnic Minority Students Perceive Patterns in Chinese Characters: Knowledge of Character Components and Structures

This chapter assesses ethnic minority (EM) adolescent Chinese as a Second Language (CSL) learners’ perception of visual patterns in Chinese characters and examines the role of component and structural knowledge in CSL beginner and intermediate level curricula. In this exploratory mixed methods study, 213 Grades 7 to 11 EM students of different ethnic origins in Hong Kong and Macau without prior training in components and spatial configurations of Chinese characters completed a set of tests that measured their character component and structural knowledge, including (i) the Separation of Character Components Test; (ii) the Constitution of Character Components Test; and (iii) the Character Structure Test. Five ways of componential analysis of Chinese characters, namely (1) unanalytical agglomeration of strokes; (2) agglomeration of sequenced strokes; (3) arbitrary repetition of (parts of) component; (4) hybrid agglomeration of strokes and components; and (5) agglomeration of components, were identified to be used by the participants. The participants’ television viewing habits had a significant effect on their performance on the test; however, overall, their demographic background and after-school activities had no significant effects on their test performance. With reference to the findings, recommendations on enhancing EM adolescent CSL learners’ orthographic awareness for literacy success are given towards the end of the chapter. In particular, an Integrative Perceptual Approach for Teaching Chinese Characters (Tse, Marton, Ki, & Loh, 2007) is recommended for teaching orthographic knowledge in a way that is beneficial to students’ all-round second language (L2) development

Long-term follow-up in a randomised controlled trial of recombinant α2-interferon in Chinese patients with chronic hepatitis B infection

72 Chinese patients who had been positive for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) for more than six months with stable serum hepatitis B virus DNA were randomised to receive recombinant α2-interferon at doses of 2.5, 5, or 10 x 106 U/m2 intramuscularly thrice weekly for 12-24 weeks, or no treatment. 6 (11%) of 54 treated and 1 (6%) of 18 control patients became HBeAg-negative at the end of therapy or after 24 weeks of follow-up. 9 (17%) of treated but none of the control patients became HBeAg-negative between completion of therapy and 12 months. Reactivation of HBV replication subsequently occurred in 7 (13%) of the treated patients and in 1 control. Thus, sustained clearance of HBeAg was achieved only in 8 (15%) of treated patients at 12 months. Between 12 and 24 months 3 (9%) of treated patients and 1 control became negative for HBeAg. None of the patients became HBsAg-negative. α2-interferon in the dose regimen used has little long-term effect in the suppression of HBV replication in Chinese patients with chronic HBV infection.link_to_subscribed_fulltex

Somatostatin inhibits (D-Arg6, Pro9-NEt) salmon gonadotropin-releasing hormone- and dopamine D1-stimulated growth hormone release from perifused pituitary cells of chinese grass carp, Ctenopharyngodon idellus

In this study, a heterologous radioimmunoassay (RIA) for grass carp GH has been validated and used to monitor the kinetics of GH release from perifused grass carp pituitary cells. To establish the anatomical specificity of GH antiserum used in this RIA, immunohistochemical staining was performed in grass carp pituitary sections. Somatotrophs recognized by this GH antiserum were located mainly in the proximal pars distalis without overlapping with gonadotrophs located in the same area or with lactotrophs located in the rostral pars distalis. The immunoreactivity of somatotrophs was abolished by preabsorbing GH antiserum with purified grass carp GH, suggesting that the possibility of a cross-reactivity of antiserum with other grass carp pituitary hormones is unlikely. Using 125I-labeled carp GH as the RIA tracer, parallelism was observed among the displacement curves of grass carp GH standard, grass carp serum, and culture medium conditioned by grass carp pituitary cells, suggesting that this RIA can be used to quantitate grass carp GH levels in biological samples. Using an in vitro column perifusion system, a superactive gonadotropin-releasing hormone (GnRH) analog (D-Arg6, Pro9-NEt)-sGnRH (sGnRHa, 0.3-30 nM), dopamine (DA, 0.1-10 μM), and the nonselective DA agonist apomorphine (0.1-10 μM) stimulated GH release from grass carp pituitary cells in a dose-dependent manner. The GH- releasing effect of DA was mimicked by the D1 agonists SKF38393 (0.1-10 μM) and SKF77434 (0.1-10 μM), but not by the D2 agonist LY171555 (3 μM). In addition, the GH response to DA (1 μM) was blocked by the D1 antagonist SCH23390 (5 μM) but not by the D2 antagonist (±) sulpiride (5 μM), suggesting that the GH-releasing action of DA is mediated through receptors resembling mammalian D1 receptors. Somatostatin-14 (SRIF14, 0.01-100 nM), unlike sGnRHa and DA, induced a dose-dependent suppression on basal GH release. At a high dose (100 nM), SRIF14 also abolished the GH responses to sGnRHa (100 nM), DA (10 μM), and the D1 agonist SKF38393 (3 μM). These results, as a whole, provide evidence that GH release in the grass carp is under the direct regulation of GnRH, DA, and SRIF at the pituitary cell level. The present study also suggests that DA D1 receptors are present in grass carp pituitary cells mediating the GH-releasing action of DA.link_to_subscribed_fulltex