Repetitive, negligible force reaching in rats induces pathological overloading of upper extremity bones.

Work-related repetitive motion disorders are costly. Immunohistochemical changes in bones resulting from repetitive reaching and grasping in 17 rats were examined. After 3-6 weeks, numbers of ED1+ macrophages and osteoclasts increased at periosteal surfaces of sites of muscle and interosseous membrane attachment and metaphyses of reach and nonreach forelimbs. These findings indicate pathological overloading leading to inflammation and subsequent bone resorption. INTRODUCTION: Sixty-five percent of all occupational illnesses in U.S. private industry are attributed to musculoskeletal disorders arising from the performance of repeated motion, yet the precise mechanisms of tissue pathophysiology have yet to be determined for work-related musculoskeletal disorders. This study investigates changes in upper extremity bone tissues resulting from performance of a voluntary highly repetitive, negligible force reaching and grasping task in rats. MATERIALS AND METHODS: Seventeen rats reached an average of 8.3 times/minute for 45-mg food pellets for 2 h/day, 3 days/week for up to 12 weeks. Seven rats served as normal or trained controls. Radius, ulna, humerus, and scapula were collected bilaterally as follows: radius and ulna at 0, 3, 4, 5, 6, and 12 weeks and humerus and scapula at 0, 4, and 6 weeks. Bones were examined for ED1-immunoreactive mononuclear cells and osteoclasts. Double-labeling immunohistochemistry was performed for ED1 (monocyte/macrophage lineage cell marker) and TRACP (osteoclast marker) to confirm that ED1+ multinucleated cells were osteoclasts. Differences in the number of ED1+ cells over time were analyzed by ANOVA. RESULTS: Between 3 and 6 weeks of task performance, the number of ED1+ mononuclear cells and osteoclasts increased significantly at the periosteal surfaces of the distal radius and ulna of the reach and nonreach limbs compared with control rats. These cells also increased at periosteal surfaces of humerus and scapula of both forelimbs by 4-6 weeks. These cellular increases were greatest at muscle attachments and metaphyseal regions, but they were also present at some interosseous membrane attachments. The number of ED1+ cells decreased to control levels in radius and ulna by 12 weeks. CONCLUSIONS: Increases in ED1+ mononuclear cells and osteoclasts indicate that highly repetitive, negligible force reaching causes pathological overloading of bone leading to inflammation and osteolysis of periosteal bone tissues.     

A leg ulcer as manifestation of metastatic squamous cell vaginal carcinoma

Cutaneous metastasis of vaginal carcinoma is extremely rare. So far, the total number of reported skin metastasis of vaginal carcinoma is only one. We present another case with an unusual manifestation of vagina carcinoma metastasis: skin metastasis presenting as a leg ulcer on the lower leg.     

A rare case of left ventricular outflow obstruction.

We report a patient with a mass originating from the anterior mitral valve leaflet causing severe left ventricular outflow tract obstruction. Noninvasive imaging provided the best diagnostic tools for diagnosis. Histological findings showed a very rare giant blood cyst of the mitral valve.     

Localization of a gene for otosclerosis to chromosome 15q25-q26

Among white adults otosclerosis is the single most common cause of hearing impairment. Although the genetics of this disease are controversial, the majority of studies indicate autosomal dominant inheritance with reduced penetrance. We studied a large multi- generational family in which otosclerosis has been inherited in an autosomal dominant pattern. Five of16 affected persons have surgically confirmed otosclerosis; the remaining nine have a conductive hearing loss but have not undergone corrective surgery. To locate the disease- causing gene we completed genetic linkage analysis using short tandem repeat polymorphisms (STRPs) distributed over the entire genome. Multipoint linkage analysis showed that only one genomic region, on chromosome 15q, generated a lod score >2.0. Additional STRPs were typed in this area, resulting in a lod score of 3.4. STRPs FES (centromeric) and D15S657 (telomeric) flank the 14. 5 cM region that contains an otosclerosis gene.      

Peritoneal fluid concentrations of interleukin-8 in women with endometriosis: relationship to stage of disease

There is increasing evidence that immunological mechanisms play a role in the pathogenesis and pathophysiology of endometriosis. It was therefore of interest to study interleukin-8 (IL-8), a chemokine, in the peritoneal fluid and peripheral blood of women undergoing laparoscopic procedures. The presence and concentrations of IL-8 in relation to endometriosis, infertility and abdominal pain were evaluated. Samples of peritoneal fluid (n = 49) and peripheral blood (n = 50) were obtained from 50 consecutive patients undergoing laparoscopic surgery for various gynaecological indications (abdominal pain, infertility, sterilization). IL-8 was present in the peritoneal fluid of most women (87%). The concentration of IL-8 in the peritoneal fluid was higher in women with endometriosis compared to women without (P = 0.02). This difference was more pronounced in early (stage 1) endometriosis (P = 0.001). IL-8 concentrations in the peritoneal fluid were also higher in women with early endometriosis compared to women with later stages of the disease (P = 0.003). Peripheral blood concentrations did not correlate with peritoneal fluid concentrations of IL-8 and/or the presence of endometriosis. We conclude that IL-8 is an important factor that may contribute to the pathogenesis of endometriosis possibly by promoting neovascularization. This information can be a guide in the development of new therapeutic approaches for the treatment of endometriosis.      

Purification and characterization of a UDP-glucosyltransferase produced by Legionella pneumophila

Legionella pneumophila is the agent of Legionnaires' disease. It invades and replicates within eukaryotic cells, including aquatic protozoans, mammalian macrophages, and epithelial cells. The molecular mechanisms of the Legionella interaction with target cells are not fully defined. In an attempt to discover novel virulence factors of L. pneumophila, we searched for bacterial enzymes with transferase activity. Upon screening ultrasonic extracts of virulent legionellae, we identified a uridine diphospho (UDP)-glucosyltransferase activity, which was capable of modifying a 45-kDa substrate in host cells. An approximately 60-kDa UDP-glucosyltransferase was purified from L. pneumophila and subjected to microsequencing. An N-terminal amino acid sequence, as well as the sequence of an internal peptide, allowed us to identify the gene for the enzyme within the unfinished L. pneumophila genome database. The intact gene was cloned and expressed in Escherichia coli, and the recombinant protein was purified and confirmed to possess an enzymatic activity similar to that of the native UDP-glucosyltransferase. We designated this gene ugt (UDP-glucosyltransferase). The Legionella enzyme did not exhibit significant homology with any known protein, suggesting that it is novel in structure and, perhaps, in function. Based on PCR data, an enzyme assay, and an immunoblot analysis, the glucosyltransferase appeared to be conserved in L. pneumophila strains but was absent from the other Legionella species. This study represents the first identification of a UDP-glucosyltransferase in an intracellular parasite, and therefore modification of a eukaryotic target(s) by this enzyme may influence host cell function and promote L. pneumophila proliferation.