Tissue-specific regulation of growth hormone (GH) receptor and insulin-like growth factor-I gene expression in the pituitary and liver of GH-deficient (lit/lit) mice and transgenic mice that overexpress bovine GH (bGH) or a bGH antagonist

GH has diverse biological actions that are mediated by binding to a specific, high-affinity cell surface receptor (GHR). Expression of GHR is tissue specific and a requirement for cellular responsiveness to GH. IGF-I is produced in multiple tissues and regulated in part by GH through GHR. In this study, we evaluated GHR and IGF-I mRNA expression in pituitary gland and compared the levels with those derived from liver of bovine GH transgenic, GH antagonist transgenic, lit/lit mice, and their respective controls using real-time RT-PCR. In liver, both GHR and IGF-I mRNA expressions were regulated in parallel with GH action in all three animal models, and there was a strong correlation between GHR and IGF-I mRNA levels. In the pituitary gland, increased expression of IGF-I mRNA in the pituitary of bovine GH transgenic mice was observed, whereas IGF-I expression in GH antagonist transgenic or lit/lit mice was similar to that observed in control animals. There were no differences of GHR mRNA levels in pituitary gland of any groups we examined. There was also no correlation between GHR and IGF-I mRNA levels in any group in the pituitary gland. In conclusion, we found that hepatic GHR and IGF-I mRNA levels were strongly correlated with each other in chronic GH excess or deficient state, and that regulation and correlation between local GHR and IGF-I mRNA levels induced by GH is different between liver and pituitary gland.     

Fc gamma receptor II (CD32) on malignant B cells influences modulation induced by anti-CD19 monoclonal antibody

Antigenic modulation is one of many factors determining the effectiveness of monoclonal antibody (MoAb)-mediated therapy. To select the isotype of a CD19 MoAb most suitable for radioimmunotherapy of patients with B-cell malignancies, we studied the influence of MoAb isotype on modulation, after binding of the MoAb to different cell-line cells. The CD19-IgG1 MoAb was found to induce modulation of CD19 antigens on Daudi cell line cells more rapidly than did its IgG2a switch variant. We provide evidence that this difference in modulation rate is caused by the expression of Fc gamma receptor II (Fc gamma RII) on these cells. Experiments aimed at elucidating the mechanism of Fc gamma RII involvement in modulation induction by CD19-IgG1 showed that Fc gamma RII did not comodulate with CD19 MoAbs. However, cocrosslinking of CD19 and Fc gamma RII with CD19-IgG1 MoAb resulted in enhanced calcium mobilization in Daudi cells. This increased signal induction accompanies the enhanced capping and subsequent modulation of CD19 antigens. Because Fc gamma RII is expressed in varying densities on malignant B cells in all differentiation stages, our results have implications for the MoAb isotype most suitable for use in MoAb-based therapy of patients with B-cell malignancies.     

Current treatment options for intracerebral hemorrhage

Intracerebral hemorrhage (ICH) remains the least treatable form of stroke. Despite ongoing attempts to find effective interventions based on the physiopathologic understanding of this disease, evidence-based medical therapies for ICH are limited to recommendations on blood pressure (BP) reduction, intracranial pressure monitoring, osmotherapy with adequate fluid resuscitation, fever and glycemic control, and seizure prophylaxis. Although the value of surgical treatment remains in doubt because of the negative results of the International Surgical Trial in Intracerebral Haemorrhage (STICH), a subgroup analysis of this study suggested better outcomes among patients with superficial hematomas who underwent surgical evacuation, supporting the ongoing STICH-II trial. Other approaches currently under study include ultra-early hemostatic therapy and BP reduction, thrombolytic therapy for intraventricular hemorrhage, and minimally invasive surgical approaches.     

Anal intraepithelial neoplasia and squamous cell carcinoma in HIV‐infected adults

Anal cancer is one of the most common non‐AIDS‐defining malignancies in the era of combination antiretroviral therapy. Its precursor lesion, anal intraepithelial neoplasia (AIN), is highly prevalent in HIV‐infected populations. More than 90% of anal squamous cell cancers are attributable to human papillomavirus (HPV). While the biology of HPV‐related intraepithelial neoplasia is consistent across lower anogenital sites, the natural history of AIN is not well established and cannot be assumed to be identical to that of cervical intraepithelial neoplasia. Screening strategies to prevent anal cancer should be developed based on robust natural history data in HIV‐infected and uninfected populations. Likewise, treatments need to be tested in randomized clinical trials, and reserved for those at significant risk of progression to cancer. This review covers the epidemiology, pathogenesis and immunology of HPV infection, AIN and anal cancer, and summarizes the current diagnosis, screening and treatment strategies in HIV‐infected adults.     

Cardiovascular Protection to Improve Clinical Outcomes After Subarachnoid Hemorrhage: Is There a Proven role?

Cardiac abnormalities seen in patients with subarachnoid hemorrhage (SAH) are considered to be a neurally mediated process rather than a manifestation of coronary artery disease. In patients with SAH, myocardial injury evidenced by troponin elevation appears to predict short and long-term outcomes independently of other conventional risk. Although incidence of electrocardiographic changes, arrhythmias and left ventricular systolic dysfunction do not independently predict the outcomes, monitoring these changes and optimizing hemodynamic status in high-grade SAH is crucial to ensure adequate cerebral perfusion and arterial oxygenation. Novel interventions that go beyond blood pressure control, prevention of re-bleeding, and aneurysm obliteration should target early physiologic derangements seen in the acute phase of SAH. The early resuscitation phase in SAH represents the greatest opportunity for impacting clinical outcome and is thus the most promising window of opportunity to demonstrate a benefit when investigating novel therapeutic strategies related to protection and modulation of cardiovascular function. Specific measures, such as the early use of beta-adrenergic antagonists, to prevent these cardiac abnormalities and ameliorate its impact on morbidity and mortality are yet to be established.     

Prognostic Factors Associated with Clinical and Economic Outcomes of Appendectomies in Children: A Multilevel Analysis in a National Retrospective Cohort Study

World Journal of Surgery - Acute appendicitis is the most common acute surgical abdominal pathology in children, and it has a large impact on morbidity and the costs incurred by health care...