Synovial chondromatosis of the metacarpophalangeal joint: case report and review of the literature

Intra-articular synovial chondromatosis in the hand is rare but should be considered in the differential diagnosis of a swollen, stiff or painful joint. Other possible diagnoses include osteoarthritis, rheumatoid arthritis, gout, trauma and chronic infection, and unless enchondral ossification of loose bodies is seen the diagnosis of synovial chondromatosis may not be made preoperatively. A 69-year-old man with synovial chondromatosis of the metacarpophalangeal joint is reported. The joint was swollen and tender. He had not sustained trauma and there was no evidence of arthritis, involvement of other joints or infection. Complete synovectomy with removal of all loose bodies was successful and his symptoms resolved. Intra-articular synovial chondromatosis is a benign condition, but spontaneous resolution is the exception and surgical synovectomy remains the most effective treatment.     

Magnetic Resonance Imaging of Corticobasal Degeneration

Corticobasal degeneration (CBD) is an adult–onset, progressive parkinsonian syndrome with strikingly asymmetrical features, and signs and symptoms referable to both cerebral cortex and basal ganglia. Although once considered rare, it is now recognized with increasing frequency during life. Eight patients with clinically diagnosed CBD and 8 age– and sex–matched patients with Parkinson's disease underwent high–field–strength magnetic resonance imaging (MRI) of the brain. MRIs were graded by a blinded neuroradiologist using a semiquantitative (0–3) scale. MRI of patients with CBD revealed significantly greater T2–weighted signal hypointensity in the putamena and globi pallidi, and ventricular enlargement. When specifically sought, asymmetrical cortical atrophy was identified in 5 of 8 CBD patients. Increased T2–weighted lenticular signal hypointensity, ventricular enlargement, and asymmetrical cortical atrophy are supportive MRI findings of CBD.     

Predictors of healthy aging in men with high life expectancies.

OBJECTIVE: The purpose of this study was to identify risk factors that consistently predict staying healthy in contrast to developing clinical illness and/or physical and mental impairments. METHODS: More than 8000 men of Japanese ancestry were followed for 28 years with repeat examinations and surveillance for deaths and incident clinical illness. Physical and cognitive functions were measured in 1993. Measures of healthy aging included surviving and remaining free of major chronic illnesses and physical and cognitive impairments. RESULTS: Of 6505 healthy men at baseline, 2524 (39%) died prior to the final exam. Of the 3263 available survivors, 41% remained free of major clinical illnesses, 40% remained free of both physical and cognitive impairment, and 19% remained free of both illness and impairment. The most consistent predictors of healthy aging were low blood pressure, low serum glucose, not smoking cigarettes, and not being obese. CONCLUSIONS: Beyond the biological effects of aging, much of the illness and disability in the elderly is related to risk factors present at midlife.     

Sexual assault and other types of sexual harassment by workplace personnel: a comparison of antecedents and consequences

Although sexual assault by workplace personnel is widely viewed as a type of sexual harassment, little is known about whether these overlapping constructs may possess some unique characteristics. This article compares the theoretical antecedents and consequences of sexual assault by workplace personnel and other types of sexual harassment among 22,372 women employed in the U.S. military. Path analysis revealed that low sociocultural and organizational power are associated with an increased likelihood of both types of victimization. Organizational climate and job gender context are directly associated with sexual harassment but are only indirectly associated with sexual assault by workplace personnel. Both types of victimization are associated with a variety of negative outcomes, but the pattern of negative consequences differs.     

Generation of targets for alloreactive CTL using purified H-2K in liposomes and polyethylene glycol

The ability of a purified major histocompatibility antigen to serve as the target cell antigen for alloreactive CTL (H-2^d anti-H-2^k) was examined. Tumor cells syngeneic with responding CTL were used as targets following modification with purified alloantigen (H-2K^k). A short incubation of tumor cells with H-2K^k liposomes followed by the addition of polyethylene glycol (PEG) yielded modified tumor cells that were recognized and lysed by CTL. The macrophage-like cell line P388D1 was readily recognized following liposome and PEG modification; apparently because these cells can withstand PEG mediated insertion of H-2K^k and lipid into their membrane. The generation of targets by PEG mediated modification was most efficient using liposomes prepared with an H-2K^k:lipid ratio of about 1:500. H-2K^k containing liposomes prepared with negatively charged phospholipids readily attached to P388D1 cells, however these cells were not targets for CTL unless PEG was added. The specificity of CTL recognition and lysis of liposome modified cells was shown by the reactivity of CTL primed against alloantigens other than H-2K^k and by antibody (anti-H-2K^k) blocking of recognition and lysis. These results demonstrate that purified H-2K^k can serve as the alloantigen for CTL lysis and suggest that the H-2 must be oriented in the target cell lipid bilayer to serve as the alloantigen for CTL mediated target cell lysis.     

Anti-idiotypic antibodies specific for HLA in heart and kidney allograft recipients

Chronic rejection is the major threat to both heart and renal allograft survival. We have explored the possibility that some patients with anti-donor HLA antibodies (Ab1) develop specific anti-idiotypic antibodies (Ab2) which suppress the production of Ab1, and subsequently, the progression of chronic rejection. analysis of Ab2 in sera obtained from Ab1 producers showed that 22% of heart and 18% of kidney recipients produced Ab2. The 4- and 5-year actuarial graft survivals in Ab2 producers were 100% and 83%, respectively, compared to 57% in patients who formed Ab1 but not Ab2 (p<0.004). Patients carrying the DR2 alleles, DRB1*1501,*1502 or*1601 were at a lower risk of producing anti-donor HLA antibodies.     

Anti-HLA class I antibody-mediated activation of the PI3K/Akt signaling pathway and induction of Bcl-2 and Bcl-xL expression in endothelial cells

Anti-human leukocyte antigen (HLA) antibodies (Ab) have long been implicated in the process of acute and chronic allograft rejection, yet their mechanism(s) of action is not well understood. The aim of this study was to determine whether ligation of HLA class I molecules by anti-HLA Ab on the surface of human endothelial cells (EC) activates the PI3 Kinase (PI3K)/Akt signaling pathway and downstream target proteins of the cell death apparatus. We report that Ab ligation of major histocompatibility complex (MHC) class I molecules on the surface of EC triggers phosphorylation of Akt, PI3K, and recruitment of PI3K and Akt into a signaling unit with focal adhesion kinase. Signaling through class I also stimulated phosphorylation of Bad and upregulated expression of Bcl-2 and Bcl-xL. Pretreatment of EC with the PI3K inhibitor wortmannin blocked class I-mediated expression of Bcl-2, but not Bcl-xL, suggesting a role for the PI3K/Akt signaling pathway in regulation of class I-induced Bcl-2 expression. The intracellular events initiated by class I ligation were influenced by the concentration of the anti-HLA Ab with the lowest tested concentrations of Ab stimulating the highest level of Akt phosphorylation, Bcl-xL and Bcl-2 expression. Consistent with the in vitro experiments, analysis of biopsy samples from heart transplant recipients with evidence of Ab-mediated rejection exhibited increased Bcl-2 expression on the vascular endothelium. These results suggest that exposure of the graft endothelium to low concentrations of anti-HLA Ab may promote cell survival by transducing signals resulting in upregulation of cell survival genes.     

Immunization with a polyprotein vaccine consisting of the T-Cell antigens thiol-specific antioxidant, Leishmania major stress-inducible protein 1, and Leishmania elongation initiation factor protects against leishmaniasis

Development of an effective vaccine against Leishmania infection is a priority of tropical disease research. We have recently demonstrated protection against Leishmania major in the murine and nonhuman primate models with individual or combinations of purified leishmanial recombinant antigens delivered as plasmid DNA constructs or formulated with recombinant interleukin-12 (IL-12) as adjuvant. In the present study, we immunized BALB/c mice with a recombinant polyprotein comprising a tandem fusion of the leishmanial antigens thiol-specific antioxidant, L. major stress-inducible protein 1 (LmSTI1), and Leishmania elongation initiation factor (LeIF) delivered with adjuvants suitable for human use. Aspects of the safety, immunogenicity, and vaccine efficacy of formulations with each individual component, as well as the polyprotein referred to as Leish-111f, were assessed by using the L. major challenge model with BALB/c mice. No adverse reactions were observed when three subcutaneous injections of the Leish-111f polyprotein formulated with either MPL-squalene (SE) or Ribi 529-SE were given to BALB/c mice. A predominant Th1 immune response characterized by in vitro lymphocyte proliferation, gamma interferon production, and immunoglobulin G2A antibodies was observed with little, if any, IL-4. Moreover, Leish-111f formulated with MPL-SE conferred immunity to leishmaniasis for at least 3 months. These data demonstrate success at designing and developing a prophylactic leishmaniasis vaccine that proved effective in a preclinical model using multiple leishmanial antigens produced as a single protein delivered with a powerful Th1 adjuvant suitable for human use.     

Cloning and characterization of a gene encoding an immunoglobulin-binding receptor on the cell surface of some members of the family Trypanosomatidae

Several members of the Trypanosomatidae family, when freshly isolated from their mammalian hosts, have immunoglobulins adsorbed to their cell surfaces. However, a significant portion of these antibody molecules is not parasite specific, i.e., the immunoglobulins are bound to the parasite's cell surface molecules via noncognitive interactions. It has been proposed that this noncognitive adsorption of immunoglobulins to the parasite is mediated by an Fc-like receptor present in several members of the Trypanosomatidae family. However, the molecular identification of this receptor has never been defined. Here, we describe the cloning of a gene encoding a protein that might represent this molecule. The gene, named Lmsp1, was cloned by screening a Leishmania major cDNA expression library using a rabbit antiserum. Lmsp1 is present in both Leishmania and Trypanosoma and is expressed in all developmental stages of these parasites. The predicted protein has a molecular mass of 16.6 kDa and contains an RGD sequence starting at residue 104 and three cysteine residues at positions 55, 74, and 116. The purified recombinant protein strongly binds to normal immunoglobulins of various animal species (humans, rabbits, sheep, goats, guinea pigs, donkeys, rats, and mice) and the binding to human immunoglobulins appears to be immunoglobulin G (IgG) and IgM isotype specific. Moreover, Lmsp1 binds to both purified Fc and Fab fragments of IgG from both humans and rabbits. The mapping of the Lmsp1 epitopes that bind human IgG revealed that different sequences of the molecule bind to Fc or Fab. In addition, fluorescence-activated cell sorter analyses with a specific rabbit anti-Lmsp1 antiserum showed that Lmsp1 is associated with the parasite's cell surface. Finally, inhibition experiments point to an active role of this molecule in the immunoglobulin-mediated attachment and penetration of Trypanosoma cruzi in its macrophage host cells, thus suggesting that Lmsp1 is a putative Trypanosomatidae immunoglobulin receptor.     

Identification of cathepsin C mutations in ethnically diverse papillon-Lefèvre syndrome patients

INTRODUCTION—Papillon-Lefèvre syndrome (PLS) is an autosomal recessive disorder characterised by palmoplantar keratoderma and severe, early onset periodontitis, which results from deficiency of cathepsin C activity secondary to mutations in the cathepsin C gene. To date, 13 different cathepsin C mutations have been reported in PLS patients, all of which are homozygous for a given mutation, reflecting consanguinity.
AIM—To evaluate the generality of cathepsin C mutations in PLS, we studied an ethnically diverse group of 20 unrelated families.
METHODS—Mutations were identified by direct automated sequencing of genomic DNA amplified for exonic regions and associated splice site junctions of the cathepsin C gene. Long range PCR was performed to determine the genomic structure of the cathepsin C gene.
RESULTS—The cathepsin C gene spans over 46 kb, with six introns ranging in size from 1.6 to 22.4 kb. Eleven novel mutations and four previously reported mutations were identified in affected subjects from 14 families. Missense mutations were most common (9/15), followed by nonsense mutations (3/15), insertions (2/15), and deletions (1/15). Among these 14 probands, two were compound heterozygotes. Affected subjects with transgressions of the dermal lesions onto the knees or elbows or both had mutations in both the pro- and mature regions of the enzyme, although most were in the mature region.
CONCLUSION—Mutations in the mature region of cathepsin C were more likely to be associated with the transgressions of the dermatological lesions, although the results were not statistically significant. A comprehensive list of all cathepsin C mutations described to date, representing 25 mutations from 32 families with PLS and related conditions, is also presented.


Keywords: cathepsin C; genetics; severe early onset periodontitis; hyperkeratosis