The expression of HSP60 and HSP10 in large bowel carcinomas with lymph node metastase

Background

Cancer serum protein profiling by mass spectrometry has uncovered mass profiles that are potentially diagnostic for several common types of cancer. However, direct mass spectrometric profiling has a limited dynamic range and difficulties in providing the identification of the distinctive proteins. We hypothesized that distinctive profiles may result from the differential expression of relatively abundant serum proteins associated with the host response.

Methods

Eighty-four antibodies, targeting a wide range of serum proteins, were spotted onto nitrocellulose-coated microscope slides. The abundances of the corresponding proteins were measured in 80 serum samples, from 24 newly diagnosed subjects with lung cancer, 24 healthy controls, and 32 subjects with chronic obstructive pulmonary disease (COPD). Two-color rolling-circle amplification was used to measure protein abundance.

Results

Seven of the 84 antibodies gave a significant difference (p < 0.01) for the lung cancer patients as compared to healthy controls, as well as compared to COPD patients. Proteins that exhibited higher abundances in the lung cancer samples relative to the control samples included C-reactive protein (CRP; a 13.3 fold increase), serum amyloid A (SAA; a 2.0 fold increase), mucin 1 and α-1-antitrypsin (1.4 fold increases). The increased expression levels of CRP and SAA were validated by Western blot analysis. Leave-one-out cross-validation was used to construct Diagonal Linear Discriminant Analysis (DLDA) classifiers. At a cutoff where all 56 of the non-tumor samples were correctly classified, 15/24 lung tumor patient sera were correctly classified.

Conclusion

Our results suggest that a distinctive serum protein profile involving abundant proteins may be observed in lung cancer patients relative to healthy subjects or patients with chronic disease and may have utility as part of strategies for detecting lung cancer.     

Effect of regular exercise on the radiographic progression of foot osteoarthritis

Among the elderly, osteoarthritis often causes chronic pain and disability. Although research has addressed the association between exercise and osteoarthritis, few studies have examined the effect of exercise on the radiographic progression of osteoarthritis. We investigated the relationship between ongoing exercise and radiographic progression of foot osteoarthritis. The first metatarsophalangeal and medial cuneiform-first tarsometatarsal joints were assessed. Joint-specific osteoarthritis radiographic progression scores were determined using four assessments: joint space narrowing, osteophytes, sclerosis, and a composite score. This cohort study included a subset of 221 men and women aged 40 to 91 years participating in a community-based osteoarthritis study. Adjusted risk estimates (95% confidence intervals) summarizing the relationship between ongoing exercise and radiographic progression in the first metatarsophalangeal joint ranged from 0.34 (0.11-0.99) for osteophytes to 0.66 (0.23-1.92) for sclerosis; because only eight individuals experienced medial cuneiform-first tarsometatarsal joint progression, these estimates were less stable, ranging from 2.41 (0.49-11.83) for composite to 4.29 (0.11-166.52) for osteophytes. Overall, our findings do not suggest that regular exercise is a risk factor for foot osteoarthritis progression. Future replication studies are warranted to confirm these findings.     

Microsurgical one-stage repair of hypospadias with a rectangular transverse dorsal preputial vascularized skin flap

A microsurgical technique for one-stage repair of hypospadias using a rectangular transverse dorsal preputial island skin flap is presented. The use of optical magnification, atraumatic technique, and microsurgical instruments allows a vascularized preputial skin flap to be raised and isolated on the dorsum of the penis and then rotated ventrally and tubulized into a neourethral channel. The meatus of the new urethral channel lies at the tip of the glans. Cover for the penis is simply obtained and does not require a longitudinal row of sutures. The need to remove the distal stenotic portion of the urethra and to correct any degree of chordee is outlined and emphasized. Good cosmetic and functional results demonstrate the efficacy of such a technique.     

Evaluation of concentration procedures of mutagenic metabolites from urine of diesel particulate-treated rats

Several concentration procedures of mutagenic metabolites contained in the urine of diesel particulate-treated rats were compared. Mutagenicity was monitored by the Salmonella/microsome assay. The procedures tested were: lyophilization; filtration on XAD-2, XAD-7 or Sephadex LH-20 matrices; ultrafiltration; and extraction with organic solvents. Urine extraction with dichloromethane (DCM) gave almost quantitative recovery of activity while leaving salts and other polar compounds in the aqueous phase, and is the method recommended.     

Endoscopic surgery for fibrous dysplasia of the sinonasal tract in pediatric patients

Fibrous dysplasia (FD) is a non-neoplastic, expansile lesion of unknown origin. In about one-fourth of cases this disorder affects the head and neck area, where the mandible and maxilla are the most frequently involved sites. Its localization to the ethmoid is a rare event. Since the disease slowly progresses, its management is delayed until significant clinical symptoms or non-well-tolerated aesthetic deformities are present. When required, surgery is the treatment of choice. Several external procedures have been used to manage the lesion, but recently, more conservative transnasal approaches have been proposed. We report the history of a 6-year-old boy with fibrous dysplasia of the ethmoid labyrinth that underwent successful transnasal endoscopic removal. Furthermore, an analysis of the literature is presented with particular emphasis on clinical picture, diagnosis, and treatment of this rare illness.     

Glatiramer acetate in multiple sclerosis: update on potential mechanisms of action

Glatiramer acetate is a synthetic random copolymer approved for the immunomodulatory therapy of relapsing-type multiple sclerosis (MS). Previous work has focused on the effects of this drug on T cells, especially the glatiramer-acetate-induced shift of the cytokine profile towards those characteristic of T-helper-2 (Th2) cells. Glatiramer acetate was thought to bring about this Th2 shift by acting like an altered peptide ligand but more recent work has shown that the drug notably affects the properties of antigen-presenting cells, such as monocytes and dendritic cells. These new observations might offer an explanation for the previously observed Th2 shift. In this review, we focus on these new findings. We address several controversial issues, including the possible neurotrophic effects of glatiramer acetate, the potential role of neutralising antibodies to the drug, and attempts to develop biomarkers of the treatment response. Finally, we will think about how a better understanding of glatiramer acetate might help the development of new immunomodulatory agents for MS.     

Henri Ey's neojacksonism and the psychopathology of disintegrated mind

The French psychiatrist Henri Ey developed his organo-dynamic theory of the mind function and consciousness 50 years ago incorporating Hughling Jackson's thinking, along with psychiatric and philosophical theorizations by Janet and Bergson. This model has not received the attention it deserved, but recent advances in neuroscience rekindled interest for Ey's theory. By overcoming the Cartesian mind-body dualism and treating the mind-body unit as an inseparable whole, this model opens the way for the integrated treatment of mental disorders. Ey's conceptualization of consciousness as being simultaneously both synchronous and diachronic anticipates current theories of consciousness (Damasio, Edelman, Mesulam).     

Preferential expression and function of Toll-like receptor 3 in human astrocytes

In contrast to other tissues, the central nervous system (CNS) is essentially devoid of MHC expression and shielded from antibodies by the blood-brain barrier. Therefore, a rapid local innate immune response by resident brain cells is required to effectively fight infectious agents. This study analyzed the expression and function of Toll-like receptors (TLRs) in cultured human astrocytes. Quantitative PCR for TLRs 1 to 10 showed a basal expression of TLR3 that could be enhanced by IFN-gamma, IL-1beta, and IFN-beta. The other TLRs were barely detectable and not inducible by the same cytokines. IFN-gamma-activated astrocytes responded to TLR3 ligand poly (I:C) engagement with IL-6 production, while ligands of other TLRs, like LPS, lipoteichoic acid, peptidoglycan, flagellin, and CpG, had no effect. Poly (I:C) also triggered astrocyte production of TNF-alpha and the chemokines CCL2/MCP-1, CCL5/RANTES, CCL20/MIP-3alpha, and CXCL10/IP-10. The adapter molecules MyD88 (full length and short isoform), TIRAP/Mal, and TICAM-1/TRIF, which are required for TLR signaling, were all expressed by astrocytes. Thus, resting and activated human astrocytes express preferentially TLR3 and, upon TLR3 engagement, produce IL-6 and chemokines active on T cells, B cells, monocytes, and dendritic cells. These data indicate that astrocytes function as sentinels for viral infections in the CNS.