Gene expression profiles of serous, endometrioid, and clear cell subtypes of ovarian and endometrial cancer.

PURPOSE: The presence of similar histologic subtypes of epithelial ovarian and endometrial cancers has long been noted, although the relevance of this finding to pathogenesis and clinical management is unclear. Despite similar clinical characteristics, histologic subtypes of cancers of the ovary and endometrium are treated according to organ of origin. This study compares the gene expression profiles of analogous histologic subtypes of cancers of the ovary and endometrium using the same genomic platform to determine the similarities and differences between these tumors. EXPERIMENTAL DESIGN: Gene expression profiles of 75 cancers (endometrioid, serous, and clear cell) of the ovary and endometrium, five renal clear cell cancers, and seven normal epithelial brushings were determined using a 11,000-element cDNA array. All images were analyzed using BRB ArrayTools. Validation was done using real-time PCR on select genes and immunohistochemical staining. RESULTS: Comparison across endometrial and ovarian cancers and serous and endometrioid tumors showed expression patterns reflecting their organ of origin. Clear cell tumors, however, showed remarkably similar expression patterns regardless of their origin, even when compared with renal clear cell samples. A set of 43 genes was common to comparisons of each of the three histologic subtypes of ovarian cancer with normal ovarian surface epithelium. CONCLUSIONS: The comparison of the gene expression profiles of endometrioid and serous subtypes of ovarian and endometrial cancer are largely unique to the combination of a particular subtype in a specific organ. In contrast, clear cell cancers show a remarkable similarity in gene expression profiles across organs (including kidney) and could not be statistically distinguished.     

Serial in vivo MR tracking of magnetically labeled neural spheres transplanted in chronic EAE mice.

Neural stem cell (NSC) transplantation has been shown to attenuate the severity of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Central to the future success of NSC transplantation in MS is the ability of transplanted cells to migrate from the site of transplantation to relevant foci of disease. Using magnetically labeled mouse neurospheres and human embryonic stem cell (hESC)-derived neurospheres, we applied serial magnetic resonance imaging (MRI) to assess the biodynamics of transplanted cell migration in a chronic mouse EAE model. Magnetic labeling did not affect the in vitro and in vivo characteristics of cells as multipotential precursors. Cell migration occurred along white matter (WM) tracts (especially the corpus callosum (CC), fimbria, and internal capsule), predominantly early in the acute phase of disease, and in an asymmetric manner. The distance of cell migration correlated well with clinical severity of disease and the number of microglia in the WM tracts, supporting the notion that inflammatory signals promote transplanted cell migration. This study shows for the first time that hESC-derived neural precursors also respond to tissue signals in an MS model, similarly to rodent cells. The results are directly relevant for designing and optimizing cell therapies for MS, and achieving a better understanding of in vivo cell dynamics and cell-tissue interactions.     

Synovial membrane and cartilage changes in an arthrosis model. Instability and impact stress model

Surgical instability and repetitive impulsive loading was used to generate degenerative changes in knee joints of rabbits. Light- and electronmicroscopy was carried out at synovial membrane and cartilage samples. The instabilised joints had early synovial inflammation, preceding overall cartilage changes. Synoviocytes were activated and showed more and dilatated cytoplasmatic organells. Invaded round cells--potentially cartilage degenerative--were seen. In the loading model no initial synovial inflammation could be seen. Focal cartilage changes were located at the weight bearing zone. Two different inductive pathways may be involved in cartilage breakdown comparing the two arthrosis models. Mechanical factors seemed to trigger cartilage changes in the loading model, an inflammatory synovial pathway is likely to initiate cartilage breakdown in the instability model. Clinical relevance: The synovial membrane has the key-position for the cartilage degeneration in posttraumatic joint affections. The therapeutic use of antiphlogistic substances is indicated to supreme inflammatory mediators from the synovial membrane. This therapeutic concept seemed not to be useful in primary mechanical induced osteoarthrosis.     

Activity measurements of calcium, sodium, potassium, and chloride after equilibrium dialysis used to show lack of evidence for protein interference with calcium electrodes

We measured the activity of Ca2+, Na+, K+, and Cl- with ion-selective electrodes after equilibrium dialysis of solutions with different albumin concentrations. The calculated Donnan ratio was the same for all ions in the same solution and increased with the albumin concentration, as predicted by the Donnan theory. The Donnan distribution ratio for Ca2+ was similar, as determined with instruments from three different manufacturers. For healthy subjects and patients with renal stone disease, we did not find any correlation between serum concentrations of ionized calcium and albumin. The discordance between measured ionized calcium and albumin-corrected total calcium depended on the correction algorithm we utilized. The difficulties of absolutely proving or disproving a protein error in these measurements are discussed, but our data are not consistent with protein being a source of error in measurements of ionized calcium.     

Ejection fraction by combined inverse Fourier analysis and second-derivative technique: Correlation with isocontour method

Summary In order to measure ejection fractions (EFs) from nuclear ventriculograms, we devised a semi-automated edge-detection technique based on a combination of inverse Fourier analysis and second-derivative techniques. Initial clinical studies showed that, for the left ventricle, our method gives EF values statistically identical with those obtained using a conventional isocontour technique. For the right ventricle, however, the values obtained using the two methods were somewhat more at variance. Despite requiring a longer processing time, the results obtained with our method are reproducible because less operator intervention is necessary.     

The types of drugs used by HIV-infected injection drug users in a multistate surveillance project: implications for intervention.

OBJECTIVES. This study sought to describe the drugs used by drug injectors infected with human immunodeficiency virus (HIV) and to determine factors associated with the primary injection drug used. METHODS. A cross-section of persons 18 years of age or older reported with HIV or acquired immunodeficiency syndrome (AIDS) to local health departments in 11 US states and cities was surveyed. RESULTS. Of 4162 persons interviewed, 1147 (28%) reported ever having injected drugs. Of these 1147 injectors, 72% primarily injected a drug other than heroin. However, the types of drugs injected varied notably by place of residence. Heroin was the most commonly injected drug in Detroit (94%) and Connecticut (48%); cocaine was the most common in South Carolina (64%), Atlanta (56%), Delaware (55%), Denver (46%), and Arizona (44%); speedball was most common in Florida (46%); and amphetamines were most common in Washington (56%). Other determinants of the type of drug primarily injected were often similar by region of residence, except for heroin use. Polysubstance abuse was common; 75% injected more than one type of drug, and 85% reported noninjected drug use. CONCLUSIONS. Preventing the further spread of HIV will require more drug abuse treatment programs that go beyond methadone, address polysubstance abuse, and adapt to local correlates of the primary drug used.