Genetic System of Artemisia maritima L.: An Overexploited Medicinal Species Under Stress

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Artemisia maritima L., a potent source of Santonin (a drug used to expel roundworms), forms isolated...     

A novel peroxisome proliferator-activated gamma (PPAR gamma) agonist,CLX-0921, has potent antihyperglycemic activity with low adipogenic potential

Agonists of the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR gamma) are pharmacologically active antihyperglycemic agents that act by increasing peripheral tissue sensitivity to insulin. Many of these agonists have antihyperglycemic activity that is directly proportional to their ability to bind and activate PPAR gamma; however, recent data bring this relationship into question. In this report we describe a new PPAR gamma agonist, CLX-0921, that is derived from a natural product. This thiazolidinedione (TZD) has a spectrum of activity that differs from commercially available TZDs. It is a weak activator of PPAR gamma (EC(50) of 0.284 micromol/L) compared to rosiglitazone (EC(50) 0.009 micromol/L). Despite this difference, the drug maintains potent glucose uptake activity in vitro and glucose-lowering activity in vivo that is equipotent to that of rosiglitazone. Moreover, CLX-0921 showed a 10-fold reduction in in vitro adipogenic potential compared to rosiglitazone. CLX-0921 also increases glycogen synthesis, an activity not typically associated with rosiglitazone or pioglitazone. Thus CLX-0921 appears to have a distinct spectrum of activity relative to other TZDs.     

"Were-wolf" cutaneous tuberculosis

Lupus vulgaris is a variant of cutaneous tuberculosis. Its more destructive and mutilating clinical forms have become rarer in consonance of a general decline of cutaneous tuberculosis. It is rarely seen now in developed countries due to stringent control measures, improved quality of living and effective therapeutic regimens. Misdiagnosis, neglect, or late diagnosis may result in severe, ulcerative and mutilating "wolf eaten" skin lesions.This paper describes four such cases of "were-wolf" cutaneous tuberculosis. Early diagnosis and treatment is important to prevent much of the disfigurement.     

Anomalous origin of the left pulmonary artery from the ascending aorta in a patient with tetralogy of Fallot and "absent pulmonary valve".

The rare association of tetralogy of Fallot, rudimentary formation of the leaflets of the pulmonary valve, and anomalous origin of the left pulmonary artery from the ascending aorta is described in a two-month-old infant. The diagnosis was made by cardiac catheterisation and angiography.     

Immunopathologic and clinical studies in pulmonary hypertension associated with systemic lupus erythematosus

PH is an uncommon manifestation of SLE. The symptoms of PH develop within a few years after the onset of the multisystem disease. The most common presenting complaints of SLE patients with PH are dyspnea on exertion, chest pain, nonproductive cough, edema, and fatigue or weakness. The important physical findings are a loud second pulmonic heart sound and a right ventricular lift. The chest roentgenogram shows a cardiomegaly, a prominent pulmonary segment, and usually clear lung fields. Pulmonary function tests may show evidence of restrictive lung disease; however, the physiologic abnormalities are mild and out of proportion to the severity of the PH. The diagnosis of PH is established by cardiac catheterization showing elevated pulmonary artery pressure, normal capillary wedge pressure, and no evidence of intracardiac or extracardiac shunts. Pathologic examination of the lung demonstrates angiomatoid lesions involving muscular pulmonary arteries. There is a thickening of the media and subintima of the arterioles. Immunoglobulin and complement deposits are found in the walls of pulmonary arteries. Immunoglobulin eluted from the lung contains rheumatoid factor and antinuclear antibody including antibody to DNA activity. DNA antigen is also present in walls of blood vessels. These results suggest an immune complex deposition process as a mechanism in the pathogenesis of PH in SLE. The clinical course of PH in SLE is variable. Symptoms may be mild and the disease follows a stable and protracted course for several years. It can, however, develop a progressive course ending in death in a few years. The clinical response of SLE patients with PH to treatment with high doses of systemic corticosteroids is not consistent or predictable.     

Cirrhosis of the liver simulating congenital cyanotic heart disease

During the last 25 years, 20 patients with cirrhosis of liver with severe cyanosis and gross clubbing simulating congenital cyanotic heart disease were subjected to cardiac catheterization and angiography, splenography, liver function tests, and liver biopsy. No portopulmonary fistulas could be demonstrated. The cyanosis and clubbing were secondary to right to left intrapulmonary shunting across multiple tiny pulmonary arteriovenous fistulas. In 15 cases, selective pulmonary angiography revealed discrete arteriovenous fistulas. In five cases, the angiogram did not reveal any convincing evidence of pulmonary arteriovenous fistulas. In two of these five cases, peripheral vein contrast echocardiography demonstrated right to left intrapulmonary shunting and seems a sensitive investigation. Open lung biopsy in one case showed evidence of pulmonary arteriovenous fistulas.     

Noncirrhotic portal fibrosis/idiopathic portal hypertension: APASL recommendations for diagnosis and treatment

The Asian Pacific Association for the Study of the Liver (APASL) Working Party on Portal Hypertension has developed consensus guidelines on the disease profile, diagnosis, and management of noncirrhotic portal fibrosis and idiopathic portal hypertension. The consensus statements, prepared and deliberated at length by the experts in this field, were presented at the annual meeting of the APASL at Kyoto in March 2007. This article includes the statements approved by the APASL along with brief backgrounds of various aspects of the disease.     

Genetic origin of lupus in NZB/SWR hybrids: lessons from an intercross study

OBJECTIVE: (SWR x NZB)F(1) (or SNF(1)) hybrid mice succumb to lupus nephritis. A previous analysis of SNF(1) x NZB backcross mice revealed the existence of 4 SWR loci (H2 on chromosome 17, Swrl-1 on chromosome 1, Swrl-2 on chromosome 14, and Swrl-3 on chromosome 18) and 2 NZB loci (Nba1 and Lbw2/Sbw2, both on chromosome 4). A second study focusing on SNF(1) x SWR backcross offspring uncovered 5 suggestive loci for antinuclear antibody formation, consisting of 3 dominant NZB contributions (Nba4 on chromosome 5, Lbw4 on chromosome 6, and Nba5 on chromosome 7) and 2 recessive SWR contributions (Swrl-1 on chromosome 1 and Swrl-4 on chromosome 10). The present intercross study was executed to replicate the earlier findings, using an independent panel of (SWR x NZB)F(2) offspring. METHODS: A panel of (NZB x SWR)F(2) hybrids were phenotyped (for renal disease, early mortality, and a variety of autoantibodies) and genotyped (using 95 microsatellite primers positioned across all 19 autosomes and the X chromosome). Linkage analysis was conducted using the derived phenotype and genotype data, with the interval-mapping program MapManager. RESULTS: Four suggestive loci were mapped: Swrl-5 on chromosome 1 (peak at 106 cM), linked to hypergammaglobulinemia; an NZB locus on chromosome 5 (Nba4; peak at 15 cM), linked to IgG anti-single-stranded DNA (anti-ssDNA) antibodies, IgG anti-doubled-stranded DNA (anti-dsDNA) antibodies, and glomerulonephritis; an NZB locus on chromosome 13 (Nba6; peak at 28 cM), linked to IgG anti-dsDNA antibodies; and an SWR locus on chromosome 14 (Swrl-2; peak at 30 cM), linked to IgG anti-ssDNA antibodies. Eight additional loci revealed linkage at P < 0.01, of which 7 co-mapped with lupus susceptibility loci previously identified in other models. CONCLUSION: Considering all 3 mapping studies together, lupus in SWR/NZB hybrids appears to be the epistatic end product of several distinct loci, of which 3 SWR-derived loci (Swrl-1, Swrl-2, and Swrl-3) and 5 NZB-derived loci (Nba1, Nba3, Nba4, Nba5, and Lbw4) have been independently confirmed. The immunologic functions and molecular identities of these loci await elucidation.     

DNA/MVA vaccine for HIV type 1: effects of codon-optimization and the expression of aggregates or virus-like particles on the immunogenicity of the DNA prime

Recently, a vaccine consisting of DNA priming followed by boosting with modified vaccinia Ankara (MVA) has provided long-term protection of rhesus macaques against a virulent challenge with a chimera of simian and human immunodeficiency viruses. Here, we report studies on the development of the DNA component for a DNA/MVA HIV vaccine for humans. Specifically, we assess the ability of a codon-optimized Gag-expressing DNA and two noncodon-optimized Gag-Pol-Env-expressing DNAs to prime the MVA booster dose. The codon-optimized DNA expressed virus-like particles (VLPs), whereas one of the noncodon-optimized DNAs expressed VLPs and the other expressed aggregates of HIV proteins. The MVA boost expressed Gag-Pol and Env and produced VLPs. Immunogenicity studies in macaques used one intramuscular prime with 600 microg of DNA and two intramuscular boosts with 1 x 10(8) pfu of MVA at weeks 8 and 30. The codon-optimized and noncodon-optimized DNAs proved similar in their ability to prime anti-Gag T cell responses. The aggregate and VLP-expressing Gag-Pol-Env DNAs also showed no significant differences in their ability to prime anti-Env Ab responses. The second MVA booster dose did not increase the peak CD4 and CD8 T cell responses, but increased anti-Env Ab titers by 40- to 90-fold. MVA-only immunizations elicited 10-100 times lower frequencies of T cells and 2-4 lower titers of anti-Env Ab than the Gag-Pol-Env DNA/MVA immunizations. Based on the breadth of the T cell response and a trend toward higher titers of anti-Env Ab, we are moving forward with human trials of the noncodon-optimized VLP-expressing DNA.