Pharmacogenomics and the Yin/Yang actions of ginseng: anti-tumor, angiomodulating and steroid-like activities of ginsenosides

In Chinese medicine, ginseng (Panax ginseng C.A. Meyer) has long been used as a general tonic or an adaptogen to promote longevity and enhance bodily functions. It has also been claimed to be effective in combating stress, fatigue, oxidants, cancer and diabetes mellitus. Most of the pharmacological actions of ginseng are attributed to one type of its constituents, namely the ginsenosides. In this review, we focus on the recent advances in the study of ginsenosides on angiogenesis which is related to many pathological conditions including tumor progression and cardiovascular dysfunctions.     

The stress kinase mitogen-activated protein kinase kinase (MKK)7 is a negative regulator of antigen receptor and growth factor receptor-induced proliferation in hematopoietic cells

The dual specificity kinases mitogen-activated protein kinase (MAPK) kinase (MKK)7 and MKK4 are the only molecules known to directly activate the stress kinases stress-activated protein kinases (SAPKs)/c-Jun N-terminal kinases (JNKs) in response to environmental or mitogenic stimuli. To examine the physiological role of MKK7 in hematopoietic cells, we used a gene targeting strategy to mutate MKK7 in murine T and B cells and non-lymphoid mast cells. Loss of MKK7 in thymocytes and mature B cells results in hyperproliferation in response to growth factor and antigen receptor stimulation and increased thymic cellularity. Mutation of mkk7 in mast cells resulted in hyperproliferation in response to the cytokines interleukin (IL)-3 and stem cell factor (SCF). SAPK/JNK activation was completely abolished in the absence of MKK7, even though expression of MKK4 was strongly upregulated in mkk7(-/-) mast cell lines, and phosphorylation of MKK4 occurred normally in response to multiple stress stimuli. Loss of MKK7 did not affect activation of extracellular signal-regulated kinase (ERK)1/2 or p38 MAPK. mkk7(-/-) mast cells display reduced expression of JunB and the cell cycle inhibitor p16INK4a and upregulation of cyclinD1. Reexpression of p16INK4a in mkk7(-/-) mast cells abrogates the hyperproliferative response. Apoptotic responses to a variety of stimuli were not affected. Thus, MKK7 is an essential and specific regulator of stress-induced SAPK/JNK activation in mast cells and MKK7 negatively regulates growth factor and antigen receptor-driven proliferation in hematopoietic cells. These results indicate that the MKK7-regulated stress signaling pathway can function as negative regulator of cell growth in multiple hematopoietic lineages.     

Pelvic osteoid osteoma in a skeletally mature female

Osteoid osteoma is the most common bone-producing tumor that typically presents with "throbbing night pain" and that improves dramatically with use of low-dose salicylates. Few cases of pelvic osteoid osteoma have been reported, and most have involved patients younger than age 30. Surgical excision classically has been the treatment of choice, but, recently, less invasive modalities, including radiofrequency ablation, have begun to supplant surgical management of osteoid osteoma, resulting in a decrease in the need for definitive surgical diagnosis and treatment. We present a rare case of osteoid osteoma in the pelvis of a woman older than age 30.     

Risk of influenza A (H5N1) infection among poultry workers, Hong Kong, 1997-1998

In 1997, outbreaks of highly pathogenic influenza A (H5N1) among poultry coincided with 18 documented human cases of H5N1 illness. Although exposure to live poultry was associated with human illness, no cases were documented among poultry workers (PWs). To evaluate the potential for avian-to-human transmission of H5N1, a cohort study was conducted among 293 Hong Kong government workers (GWs) who participated in a poultry culling operation and among 1525 PWs. Paired serum samples collected from GWs and single serum samples collected from PWs were considered to be anti-H5 antibody positive if they were positive by both microneutralization and Western blot testing. Among GWs, 3% were seropositive, and 1 seroconversion was documented. Among PWs, approximately 10% had anti-H5 antibody. More-intensive poultry exposure, such as butchering and exposure to ill poultry, was associated with having anti-H5 antibody. These findings suggest an increased risk for avian influenza infection from occupational exposure.     

Mammalian Mst1 and Mst2 kinases play essential roles in organ size control and tumor suppression

Control of organ size by cell proliferation and survival is a fundamental developmental process, and its deregulation leads to cancer. However, the molecular mechanism underlying organ size control remains elusive in vertebrates. In Drosophila, the Hippo (Hpo) signaling pathway controls organ size by both restricting cell growth and proliferation and promoting cell death. Here we investigated whether mammals also require the Hpo pathway to control organ size and adult tissue homeostasis. We found that Mst1 and Mst2, the two mouse homologs of the Drosophila Hpo, control the sizes of some, but not all organs, in mice, and Mst1 and Mst2 act as tumor suppressors by restricting cell proliferation and survival. We show that Mst1 and Mst2 play redundant roles, and removal of both resulted in early lethality in mouse embryos. Importantly, tumors developed in the liver with a substantial increase of the stem/progenitor cells by 6 months after removing Mst1 and Mst2 postnatally. We show that Mst1 and Mst2 were required in vivo to control Yap phosphorylation and activity. Interestingly, apoptosis induced by TNFα was blocked in the Mst1 and Mst2 double-mutant cells both in vivo and in vitro. As TNFα is a pleiotropic inflammatory cytokine affecting most organs by regulating cell proliferation and cell death, resistance to TNFα-induced cell death may also contribute significantly to tumor formation in the absence of Mst1 and Mst2.     

Performance of a Novel Point-of-Care Molecular Assay for Detection of Influenza A and B Viruses and Respiratory Syncytial Virus (Enigma MiniLab) in Children with Acute Respiratory Infection

The performance of the Enigma MiniLab assay for influenza A and B viruses and respiratory syncytial virus (RSV) was compared to a centralized laboratory respiratory virus panel. The positive and negative percent agreement for influenza A virus, influenza B virus, and RSV were 79.2% (95% confidence interval [95% CI], 57.8 to 92.9%) and 99.4% (95% CI, 98.4 to 99.9), 100% (95% CI, 47.8 to 100%) and 100% (95% CI, 99.3 to 100%), 98.5% (95% CI, 94.6 to 99.8%) and 94.5% (95% CI, 91.9 to 96.4%), respectively.     

Attribution Model of Stigma towards Children with Autism in Hong Kong

Background Accounting for the effects of knowledge of and experience with autism, the relationships of cognitive attribution (perceived controllability), emotions (anger and sympathy), as well as helping and punitive behavioural intentions towards children with autism were examined. Based on the attribution model, mediating effects of anger and sympathy on cognitive attributions and behavioural intentions were tested. Materials and Methods 123 frontline staff in educational settings completed a modified version of the Attribution Questionnaire after reading a hypothetical vignette and completing a quiz on autism. Results Knowledge and experience were only significantly related to punitive behavioural intention towards children with autism. Anger and sympathy mediated the effect between perceived controllability on both helping and punitive behavioural intentions. Conclusions The intentional responses towards children with autism were strongly related to their emotional reactions. Thus, in addition to educating frontline staff about autism, training them on emotion regulation is equally important in autism stigma reduction.     

Emerging concepts in the management of acute myocardial infarction in patients with diabetes mellitus

Although fibrinolysis has improved survival of patients after myocardial infarction (MI), such therapy is less likely to be administered to patients with diabetes. Furthermore, these patients present later (15 min) than nondiabetics. Moreover, even with the use of early potent fibrinolytic agents, patients with diabetes continued to suffer excessive morbidity and mortality. This finding is not related to the ability of fibrinolytic agents to restore complete reperfusion or increased risk of reocclusion of the infarct-related artery. Instead, the impaired ventricular performance at the noninfarct areas and metabolic derangements during the acute phase of MI may account for the adverse outcome. The efficacy of percutaneous coronary revascularization procedures for treatment of acute MI requires further evaluation. Therapeutic approaches should consider correcting these abnormalities to afford greater survival benefit for this subset of high-risk patients.     

Albuterol-induced downregulation of Gsalpha accounts for pulmonary beta(2)-adrenoceptor desensitization in vivo

The aim of the present study was to develop a chronic in vivo model of pulmonary beta(2)-adrenoceptor desensitization and to elucidate the nature and molecular basis of this state. Subcutaneous infusion of rats with albuterol for 7 days compromised the ability of albuterol, given acutely, to protect against acetylcholine-induced bronchoconstriction. The bronchoprotective effect of prostaglandin E(2), but not forskolin, was also impaired, indicating that the desensitization was heterologous and that the primary defect in signaling was upstream of adenylyl cyclase. beta(2)-Adrenoceptor density was reduced in lung membranes harvested from albuterol-treated animals, and this was associated with impaired albuterol-induced cyclic adenosine monophosphate (cAMP) accumulation and activation of cAMP-dependent protein kinase ex vivo. Gsalpha expression was reduced in the lung and tracheae of albuterol-treated rats, and cholera toxin-induced cAMP accumulation was blunted. Chronic treatment of rats with albuterol also increased cAMP phosphodiesterase activity and G protein-coupled receptor kinase-2, but the extent to which these events contributed to beta(2)-adrenoceptor desensitization was unclear given that forskolin was active in both groups of animals and that desensitization was heterologous. Collectively, these results indicate that albuterol effects heterologous desensitization of pulmonary Gs-coupled receptors in this model, with downregulation of Gsalpha representing a primary molecular etiology.     

Polymerase chain reaction amplification of herpes simplex virus DNA from clinical samples.

The polymerase chain reaction was used to amplify herpes simplex virus (HSV) DNA from 79 clinical specimens from the female genital tract, and the results were compared with cell culture. Combining the polymerase chain reaction with visualization of amplified products using a direct gel analysis, HSV DNA was detected in 38 specimens, six of which were negative for virus by cell culture. Hybridization of the amplified products detected HSV in three other specimens. One specimen was positive for HSV by cell culture but negative for viral DNA by polymerase chain reaction. Specimen purification before the polymerase chain reaction improved the detection of viral DNA. Restriction endonuclease cleavage of amplified DNA seen by direct gel analysis, used to differentiate HSV-1 from HSV-2, was correct in each case. The analysis time using the polymerase chain reaction was 8-10 hours, making this technique potentially valuable in the clinical setting of parturition.