Publications

The accessory Sec (SecA2/Y2) systems of streptococci and staphylococci are dedicated to the transport of large serine-rich repeat (SRR) glycoproteins to the bacterial cell surface. The means by which the glycosylated preproteins are selectively recognized by the accessory Sec system have not been fully characterized. In Streptococcus gordonii, the SRR glycoprotein GspB has a 90-residue amino-terminal signal sequence that is essential for transport by SecA2/Y2 but is not sufficient to mediate the transport of heterologous proteins by this specialized transporter. We now report that a preprotein must remain at least partially unfolded prior to transport by the accessory Sec system. In addition, a region of approximately 20 residues from the amino-terminal end of mature GspB (the accessory Sec transport or AST domain) is essential for SecA2/Y2-dependent transport. The replacement of several AST domain residues with glycine strongly interferes with export, which suggests that a helical conformation may be important. Analysis of GspB variants with alterations in the AST domain, in combination with the results with a SecY2 variant, indicates that the AST domain is essential both for targeting to the SecA2/Y2 translocase and for initiating translocation through the SecY2 channel. The combined results suggest a unique mechanism that ensures the transport of a single substrate by the SecA2/Y2 system.

Intermuscular adipose tissue (IMAT) is associated with metabolic abnormalities similar to those associated with visceral adipose tissue (VAT). Increased IMAT has been found in obese human immunodeficiency virus (HIV)-infected women. We hypothesized that IMAT, like VAT, would be similar or increased in HIV-infected persons compared with healthy controls, despite decreases in subcutaneous adipose tissue (SAT) found in HIV infection. In the second FRAM (Study of Fat Redistribution and Metabolic Change in HIV infection) exam, we studied 425 HIV-infected subjects and 211 controls (from the Coronary Artery Risk Development in Young Adults study) who had regional AT and skeletal muscle (SM) measured by magnetic resonance imaging (MRI). Multivariable linear regression identified factors associated with IMAT and its association with metabolites. Total IMAT was 51% lower in HIV-infected participants compared with controls (P = 0.003). The HIV effect was attenuated after multivariable adjustment (to -28%, P < 0.0001 in men and -3.6%, P = 0.70 in women). Higher quantities of leg SAT, upper-trunk SAT, and VAT were associated with higher IMAT in HIV-infected participants, with weaker associations in controls. Stavudine use was associated with lower IMAT and SAT, but showed little relationship with VAT. In multivariable analyses, regional IMAT was associated with insulin resistance and triglycerides (TGs). Contrary to expectation, IMAT is not increased in HIV infection; after controlling for demographics, lifestyle, VAT, SAT, and SM, HIV(+) men have lower IMAT compared with controls, whereas values for women are similar. Stavudine exposure is associated with both decreased IMAT and SAT, suggesting that IMAT shares cellular origins with SAT.

This article describes the submucosal injection technique applied in the endoscopic resection of non-polypoid colorectal neoplasms, with an emphasis on a particular technique, the dynamic submucosal injection technique.

Endoscopic mucosal resection (EMR) is preferred to standard polypectomy for the resection of non-polypoid lesions because these lesions can be technically difficult to capture with a snare; furthermore, without submucosal injection the underlying muscularis propria may be excessively coagulated or even inadvertently resected. Because the resection plane of EMR is in the middle or deeper part of the submucosa, EMR allows the precise depth of the lesion to be evaluated. Although the majority of non-polypoid lesions are adenomatous, non-polypoid colorectal neoplasm has a high association with advanced pathology, irrespective of size. Using EMR, a complete pathologic specimen is obtained, the risk of lymph node metastasis can be accurately assessed based on the depth of invasion, and patients can be suitably managed. Used according to its indications, EMR provides curative resection, and obviates the higher morbidity, mortality, and cost associated with surgical treatment.

BACKGROUND

Ciguatoxins are extremely potent neurotoxins, produced by tropical marine dinoflagellates, that persistently enter into our food web. Over 100,000 people annually experience acute ciguatera poisoning from consuming toxic fish. Roughly 5% of these victims will develop chronic ciguatera (CC), a widespread, multisymptom, multisystem, chronic illness that can last tens of years. CC is marked by disproportionate disability and non-specific refractory symptoms such as fatigue, cognitive deficits and pain, and is suggestive of other illnesses. Its unknown pathophysiology makes both diagnosis and treatment difficult.

OBJECTIVES

We wanted to compare objective parameters of visual contrast sensitivity testing, measures of innate immune response and genetic markers in cases to controls to assess the potential for the presence of persistent inflammatory parameters that are demonstrated in other biotoxin associated illnesses at a single specialty clinic.

METHODS

Using 59 CC cases and 59 controls we present in retrospective review, in all cases, abnormalities in immune responses paralleling the chronic systemic inflammatory response syndrome seen in several other chronic diseases.

RESULTS

This study defines a preliminary case definition using medical history, total symptoms, visual contrast sensitivity, HLA DR genotype analysis, reduction of regulatory neuropeptides VIP and MSH, and multiple measures of inflammatory immune response, especially C4a and TGFβ1, thereby providing a basis for identification and targeted therapy.

CONCLUSIONS

CC provides a model for chronic human illness associated with initiation of inflammatory responses by biologically produced neurotoxins.