Introduction to Disease, Human Health, and Regional Growth and Development in Asia

We have two objectives in this book. First, we bring together in one place, original research that sheds light on the myriad connections between disease, human health, and regional economic growth and development. Second, given the contemporary salience of Asia in world affairs, we concentrate on the trinity of disease, human health, and regional economic growth and development in different regions within Asia. Following this introductory chapter, there are nine chapters and each of these chapters—written by an expert or by a team of experts—discusses a particular research question or questions about disease, human health, and regional economic growth and development within Asia

The association between antihypertensive drugs and glioma

We pursued an association between hypertension and gliomas by investigating whether antihypertensive drugs (AHD) are associated with an increased glioma risk by a population-based nested case–control study using the PHARMO database; this links dispensing records of prescription drugs to hospital discharge data on an individual basis. Pathological data were derived from the Dutch nationwide registry of histo- and cytopathology. A total of 306 glioma cases incident between 1997 and 2003 were matched to 1108 controls for year of birth, sex, geographical region and duration of follow-up. Exposure was defined as cumulative duration of AHD use and, in an alternative analysis, as cumulative dose. We estimated the magnitude of the association with conditional logistic regression analysis. Cumulative use of any AHD for more than 6 months was associated with an increased risk of glioma (OR 1.45; 95% CI 1.03–2.04). After stratification for different groups of AHD, no significantly increased risk of glioma was found for any class of AHD. After excluding a latency period of 3 years before the date of diagnosis, no association was found. In conclusion, the use of AHD seems to be associated with an increased risk of glioma, but this is probably not causal

Biological therapies in the systemic management of psoriasis: International Consensus Conference

Psoriasis is a chronic, immune-mediated disorder that usually requires long-term treatment for control. Approximately 25% of patients have moderate to severe disease and require phototherapy, systemic therapy or both. Despite the availability of numerous therapeutic options, the long-term management of psoriasis can be complicated by treatment-related limitations. With advances in molecular research and technology, several biological therapies are in various stages of development and approval for psoriasis. Biological therapies are designed to modulate key steps in the pathogenesis of psoriasis. Collectively, biologicals have been evaluated in thousands of patients with psoriasis and have demonstrated significant benefit with favourable safety and tolerability profiles. The limitations of current psoriasis therapies, the value of biological therapies for psoriasis, and guidance regarding the incorporation of biological therapies into clinical practice are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72815/1/j.1365-2133.2004.06070.x.pd

Right-handed Sneutrino Dark Matter in Supersymmetric B-L Model

We show that the lightest right-handed sneutrino in TeV scale supersymmetric B-L model with inverse seesaw mechanism is a viable candidate for cold dark matter. We find that it accounts for the observed dark matter relic abundance in a wide range of parameter space. The spin-independent cross section of B-L right-handed sneutrino is consistent with the recent results CDMS II and XENON experiments and it is detectable in future direct detection experiments. Although the B-L right-handed sneutrinos annihilate into leptons, the PAMELA results can not be explained in this model unless a huge boost factor is considered. Also the muon flux generated by B-L right-handed sneutrino in the galactic center is smaller than Super-Kamiokande's upper bound.Comment: 16 pages, 7 figures; version accepted for publication in Journal of High Energy Physic

Evidence for Hitchhiking of Deleterious Mutations within the Human Genome

Deleterious mutations present a significant obstacle to adaptive evolution. Deleterious mutations can inhibit the spread of linked adaptive mutations through a population; conversely, adaptive substitutions can increase the frequency of linked deleterious mutations and even result in their fixation. To assess the impact of adaptive mutations on linked deleterious mutations, we examined the distribution of deleterious and neutral amino acid polymorphism in the human genome. Within genomic regions that show evidence of recent hitchhiking, we find fewer neutral but a similar number of deleterious SNPs compared to other genomic regions. The higher ratio of deleterious to neutral SNPs is consistent with simulated hitchhiking events and implies that positive selection eliminates some deleterious alleles and increases the frequency of others. The distribution of disease-associated alleles is also altered in hitchhiking regions. Disease alleles within hitchhiking regions have been associated with auto-immune disorders, metabolic diseases, cancers, and mental disorders. Our results suggest that positive selection has had a significant impact on deleterious polymorphism and may be partly responsible for the high frequency of certain human disease alleles

Repeated BCG treatment of mouse bladder selectively stimulates small GTPases and HLA antigens and inhibits single-spanning uroplakins

<p>Abstract</p> <p>Background</p> <p>Despite being a mainstay for treating superficial bladder carcinoma and a promising agent for interstitial cystitis, the precise mechanism of Bacillus Calmette-Guerin (BCG) remains poorly understood. It is particularly unclear whether BCG is capable of altering gene expression beyond its well-recognized pro-inflammatory effects and how this relates to its therapeutic efficacy. The objective of this study was to determine differentially expressed genes in the mouse bladder following repeated intravesical BCG therapy.</p> <p>Methods</p> <p>Mice were transurethrally instilled with BCG or pyrogen-free on days 1, 7, 14, and 21. Seven days after the last instillation, urothelia along with the submucosa was removed and amplified ds-DNA was prepared from control- and BCG-treated bladder mucosa and used to generate suppression subtractive hybridization (SSH). Plasmids from control- and BCG-specific differentially expressed clones and confirmed by Virtual Northern were then purified and the inserts were sequenced and annotated. Finally, chromatin immune precipitation combined with real-time polymerase chain reaction assay (ChIP/Q-PCR) was used to validate SSH-selected transcripts.</p> <p>Results</p> <p>Repeated intravesical BCG treatment induced an up regulation of genes associated with antigen presentation (B2M, HLA-A, HLA-DQA1, HLA-DQB2, HLA-E, HLA-G, IGHG, and IGH) and representatives of two IFNγ-induced small GTPase families: the GBPs (GBP1, GBP2, and GBP5) and the p47GTPases (IIGTP1, IIGTP2, and TGTP). Genes expressed in saline-treated bladders but down-regulated by BCG included: the single-spanning uroplakins (UPK3a and UPK2), SPRR2G, GSTM5, and RSP 19.</p> <p>Conclusion</p> <p>Here we introduced a hypothesis-generator approach to determine key genes involved in the urothelium/sumbmucosa responses to BCG therapy. Urinary bladder responds to repeated BCG treatment by up-regulating not only antigen presentation-related genes, but also GBP and p47 small GTPases, both potentially serving to mount a resistance to the replication of the <it>Mycobacterium</it>. It will be of tremendous future interest to determine whether these immune response cascades play a role in the anti-cancer effects exerted by BCG.</p

Systemic administration of IGF-I enhances healing in collagenous extracellular matrices: evaluation of loaded and unloaded ligaments

BACKGROUND: Insulin-like growth factor-I (IGF-I) plays a crucial role in wound healing and tissue repair. We tested the hypotheses that systemic administration of IGF-I, or growth hormone (GH), or both (GH+IGF-I) would improve healing in collagenous connective tissue, such as ligament. These hypotheses were examined in rats that were allowed unrestricted activity after injury and in animals that were subjected to hindlimb disuse. Male rats were assigned to three groups: ambulatory sham-control, ambulatory-healing, and hindlimb unloaded-healing. Ambulatory and hindlimb unloaded animals underwent surgical disruption of their knee medial collateral ligaments (MCLs), while sham surgeries were performed on control animals. Healing animals subcutaneously received systemic doses of either saline, GH, IGF-I, or GH+IGF-I. After 3 weeks, mechanical properties, cell and matrix morphology, and biochemical composition were examined in control and healing ligaments. RESULTS: Tissues from ambulatory animals receiving only saline had significantly greater strength than tissue from saline receiving hindlimb unloaded animals. Addition of IGF-I significantly improved maximum force and ultimate stress in tissues from both ambulatory and hindlimb unloaded animals with significant increases in matrix organization and type-I collagen expression. Addition of GH alone did not have a significant effect on either group, while addition of GH+IGF-I significantly improved force, stress, and modulus values in MCLs from hindlimb unloaded animals. Force, stress, and modulus values in tissues from hindlimb unloaded animals receiving IGF-I or GH+IGF-I exceeded (or were equivalent to) values in tissues from ambulatory animals receiving only saline with greatly improved structural organization and significantly increased type-I collagen expression. Furthermore, levels of IGF-receptor were significantly increased in tissues from hindlimb unloaded animals treated with IGF-I. CONCLUSION: These results support two of our hypotheses that systemic administration of IGF-I or GH+IGF-I improve healing in collagenous tissue. Systemic administration of IGF-I improves healing in collagenous extracellular matrices from loaded and unloaded tissues. Growth hormone alone did not result in any significant improvement contrary to our hypothesis, while GH + IGF-I produced remarkable improvement in hindlimb unloaded animals

Mixed emotions: The contribution of alexithymia to the emotional symptoms of autism

It is widely accepted that autism is associated with disordered emotion processing, and in particular, with deficits of emotional reciprocity such as impaired emotion recognition and reduced empathy. However, a close examination of the literature reveals wide heterogeneity within the autistic population with respect to emotional competence. Here we argue that, where observed, emotional impairments are due to alexithymia - a condition that frequently co-occurs with autism - rather than a feature of autism per se. Alexithymia is a condition characterized by a reduced ability to identify and describe one’s own emotion, but which results in reduced empathy and an impaired ability to recognize the emotions of others. We briefly review studies of emotion processing in alexithymia, and in autism, before describing a recent series of studies directly testing this ‘alexithymia hypothesis’. If found to be correct, the alexithymia hypothesis has wide-reaching implications for the study of autism, and how we might best support sub-groups of autistic individuals with, and without, accompanying alexithymia. Finally, we note the presence of elevated rates of alexithymia, and inconsistent reports of emotional impairments, in eating disorders, schizophrenia, substance abuse, Parkinson’s Disease, Multiple Sclerosis, and anxiety disorders. We speculate that examining the contribution of alexithymia to the emotional symptoms of these disorders may bear fruit in the same way that it is starting to do in autism