A novel peptide antagonist of the human growth hormone receptor.

Excess circulating human growth hormone (hGH) in vivo is linked to metabolic and growth disorders such as cancer, diabetes, and acromegaly. Consequently, there is considerable interest in developing antagonists of hGH action. Here, we present the design, synthesis, and characterization of a 16-residue peptide (site 1-binding helix [S1H]) that inhibits hGH-mediated STAT5 phosphorylation in cultured cells. S1H was designed as a direct sequence mimetic of the site 1 mini-helix (residues 36-51) of wild-type hGH and acts by inhibiting the interaction of hGH with the human growth hormone receptor (hGHR). In vitro studies indicated that S1H is stable in human serum and can adopt an α-helix in solution. Our results also show that S1H mitigates phosphorylation of STAT5 in cells co-treated with hGH, reducing intracellular STAT5 phosphorylation levels to those observed in untreated controls. Furthermore, S1H was found to attenuate the activity of the hGHR and the human prolactin receptor, suggesting that this peptide acts as an antagonist of both lactogenic and somatotrophic hGH actions. Finally, we used alanine scanning to determine how discrete amino acids within the S1H sequence contribute to its structural organization and biological activity. We observed a strong correlation between helical propensity and inhibitory effect, indicating that S1H-mediated antagonism of the hGHR is largely dependent on the ability for S1H to adopt an α-helix. Taken together, these results show that S1H not only acts as a novel peptide-based antagonist of the hGHR but can also be applied as a chemical tool to study the molecular nature of hGH-hGHR interactions.

Comparison between visual inspection of cervix and cytology based screening procedures in Bangladesh.

BACKGROUND: Cervical cancer continues to be a major problem in Bangladesh with approximately 18,000 new cases annually of which over 10,000 women die from it. Visual inspection of the cervix after 3-5% acetic acid (VIA) application is a simple and easy to learn method for cervical cancer screening, although cytology-based screening is more often applied in developed countries where it has successfully reduced the prevalence of cervical cancer. OBJECTIVE: To compare the efficacy of VIA and cytology-based primary methods for cervical cancer screening in Bangladesh. MATERIALS AND METHODS: This hospital based comparative study was conducted at the VIA centre and Colposcopy Clinic of Bangabandhu Sheikh Mujib Medical University (BSMMU) from October 2008 to October 2010. RESULTS: Among 650 women, 74 (11.4%) were VIA+ve and 8 (1.2%) had abnormalities in their Pap smear reports. During colposcopy, 38 (7.7%) women had different grades of CIN and 4 (0.6%) had cervical cancer. The gold standard histology findings proved 20 women had CIN I, 14 had CIN II/II and 4 had cervical cancer. Among the 38 histology diagnosed abnormalities, VIA test could identify 30 abnormalities including two cervical cancers. However, Pap smear could detect only 8 cases of histological abnormalities (2 low grade and 6 had high grade lesion) and it missed all the cervical cancer cases. The sensitivity and specificity of VIA were 88.9% and 52.1%. The positive predictive value (PPV) and negative predictive value (NPV) were 41.0%, and 92.6% respectively. Moreover, the sensitivity, specificity, PPV and NPV of Pap smear were 33.3%, 95.8%, 75.0% and 79.3%, respectively. CONCLUSIONS: VIA test should be used as the primary screening tool even with its low sensitivity and specificity in low resource countries like Bangladesh. False positive results may be greater, but overtreatment can be minimized by colposcopy evaluation of the VIA positive women.