Transcriptome analysis provides insight into venom evolution in a seed-parasitic wasp, Megastigmus spermotrophus.

One of the most striking host range transitions is the evolution of plant parasitism from animal parasitism. Parasitoid wasps that have secondarily evolved to attack plants (ie gall wasps and seed-feeders) demonstrate intimate associations with their hosts, yet the mechanism of plant-host manipulation is currently not known. There is, however, emerging evidence suggesting that ovipositional secretions play a role in plant manipulation. To investigate whether parasites have modified pre-existing adaptations to facilitate dramatic host shifts we aimed to characterize the expression of venom proteins in a plant parasite using a collection of parasitoid venom sequences as a guide. The transcriptome of a seed-feeding wasp, Megastigmus spermotrophus, was assembled de novo and three putative venoms were found to be highly expressed in adult females. One of these putative venoms, aspartylglucosaminidase, has been previously identified as a major venom component in two distantly related parasitoid wasps (Asobara tabida and Leptopilina heterotoma) and may have originated via gene duplication within the Hymenoptera. Our study shows that M. spermotrophus, a specialized plant parasite, expresses putative venom transcripts that share homology to venoms identified in Nasonia vitripennis (both superfamily Chalcidoidea), which suggests that M. spermotrophus may have co-opted pre-existing machinery to develop as a plant parasite.

The heterogeneity in risk factors of lung cancer and the difference of histologic distribution between genders in Taiwan.

OBJECTIVE: The difference in histologic patterns of lung cancer between men and women in Taiwan may be associated with the heterogeneity in causal factors of lung cancer between the sexes. A sex- and age-matched case-control study was designed to investigate such a relationship. METHODS: Cases consisted of 236 male and 291 female incident cases with newly diagnosed and histologically confirmed primary carcinoma of the lung, and were compared to one or two individually matched controls. RESULTS: Cigarette smoking, occupations, and previous tuberculosis history were found to independently correlate with an elevated risk of squamous/small cell carcinoma and adenocarcinoma for male patients. However, there was little difference in the effect of these risk factors except smoking. The use of fume extractors in the kitchen, and the habit of waiting to fry after the fumes were emitted, separately explained the majority of the attributable fraction of female squamous/small cell carcinoma (28.2%) and adenocarcinoma (47.7%). With the exception of a kitchen with fume extractors and a clinical history of tuberculosis, the environmental causal factors of lung cancer were heterogeneous between these two histologic cell groups. CONCLUSIONS: Our results suggested that the causal factors of lung cancer might be specific for the type of tumor concerned. The gender-specific risk factors of lung cancer could partly explain the difference in cell-type distribution between men and women.

Relapsing polychondritis.

Relapsing polychondritis, an uncommon, chronic, multisystem disorder characterized by recurrent episodes of inflammation of cartilaginous tissues, can be life-threatening, debilitating, and difficult to diagnose. This review is based on the authors' experience with 36 patients with relapsing polychondritis who were followed from 1980 to 1997, 30 patients located elsewhere who completed a detailed questionnaire and interview, and a perusal of English-language textbooks and papers located by a systematic search of the MEDLINE database. Relapsing polychondritis can present in a highly ambiguous fashion; therefore, in the authors' series, the mean delay from the time medical attention was sought because of symptom onset until diagnosis was 2.9 years. Although prednisone was the main form of treatment, methotrexate seemed to be of additional value. Survival was much more favorable than previously thought. Greater awareness of relapsing polychondritis would probably lead to earlier diagnosis and better outcomes.

Treatment of rheumatoid arthritis with oral type II collagen. Results of a multicenter, double-blind, placebo-controlled trial.

OBJECTIVE: Oral administration of cartilage-derived type II collagen (CII) has been shown to ameliorate arthritis in animal models of joint inflammation, and preliminary studies have suggested that this novel therapy is clinically beneficial and safe in patients with rheumatoid arthritis (RA). The present study was undertaken to test the safety and efficacy of 4 different dosages of orally administered CII in patients with RA. METHODS: Two hundred seventy-four patients with active RA were enrolled at 6 different sites and randomized to receive placebo or 1 of 4 dosages (20, 100, 500, or 2,500 microg/day) of oral CII for 24 weeks. Efficacy parameters were assessed monthly. Cumulative response rates (percentage of patients meeting the criteria for response at any time during the study) were analyzed utilizing 3 sets of composite criteria: the Paulus criteria, the American College of Rheumatology criteria for improvement in RA, and a requirement for > or = 30% reduction in both swollen and tender joint counts. RESULTS: Eighty-three percent of patients completed 24 weeks of treatment. Numeric trends in favor of the 20 microg/day treatment group were seen with all 3 cumulative composite measures. However, a statistically significant increase (P = 0.035) in response rate for the 20 microg/day group versus placebo was detected using only the Paulus criteria. The presence of serum antibodies to CII at baseline was significantly associated with an increased likelihood of responding to treatment. No treatment-related adverse events were detected. The efficacy seen with the lowest dosage is consistent with the findings of animal studies and with known mechanisms of oral tolerance in which lower doses of orally administered autoantigens preferentially induce disease-suppressing regulatory cells. CONCLUSION: Positive effects were observed with CII at the lowest dosage tested, and the presence of serum antibodies to CII at baseline may predict response to therapy. No side effects were associated with this novel therapeutic agent. Further controlled studies are required to assess the efficacy of this treatment approach.

Suppression of collagen-induced arthritis through adenovirus-mediated transfer of a modified tumor necrosis factor alpha receptor gene.

OBJECTIVE: To evaluate the efficacy of systemic and intraarticular adenoviral transfer of a modified tumor necrosis factor alpha receptor (TNF alphaR) gene and its expression in rat collagen-induced arthritis (CIA). METHODS: Rats with CIA received injections of replication-deficient adenovirus containing either a TNF alpha inhibitor (TNFI) gene or a control beta-galactosidase (beta-gal) gene. The TNFI gene codes for a fusion protein consisting of the human 55-kd TNF alphaR and a mouse IgG heavy chain. Successful gene transfer was determined by serum TNF alphaR measurements and by histologic examination of injected joints with in situ blue staining. RESULTS: Serum TNF alphaR levels were detectable for 8 days following systemic TNFI gene transfer. CIA severity was significantly suppressed by TNFI gene transfer, both prior to and following arthritis onset (P = 0.0001, by repeated-measures 2-factor analysis of variance). Direct synovial TNFI gene transfer was successful, but induced an inflammatory response without any net TNFI benefit. CONCLUSION: Systemic adenoviral-mediated transfer of the TNFI gene suppressed CIA during its transitory expression. Intraarticular gene transfer was limited by an adenoviral synovitis that was not overcome by delivery of the TNFI gene. TNFI is an excellent protein candidate for further therapeutic study.